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Sample records for murine epidermal maintenance

  1. Improved conditions for murine epidermal cell culture.

    PubMed

    Fischer, S M; Viaje, A; Harris, K L; Miller, D R; Bohrman, J S; Slaga, T J

    1980-02-01

    An improved method for cultivating newborn mouse epidermal cells has been developed that increases the longevity, epithelial nature and efficiency of cell-line establishment. The use of Super Medium, an enriched Waymouth's formulation, increased proliferation for long periods of time, as did incubation at 31 degrees C rather than 37 degrees C. The fetal bovine serum requirement was found to be reduced at the lower temperature. An increase in labeling indices was seen when epidermal growth factor (EGF) or the cyclic nucleotides were added and the presence of EGF receptors was determined. Of the prostaglandins (PG) examined, PGE1 and PGE2 produced the greatest increase in DNA synthesis. The PG precursors, arachidonic and 8,11,14-eicosatrienoic acid, were also greatly stimulatory. The use of a lethally irradiated 3T3 feeder layer at 31 degrees C proved superior in maintenance of an epithelial morphology. Subculturable cell lines were established much more readily and reproducibly in carcinogen-treated cultures grown under the improved conditions.

  2. 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

  3. TLR7-expressing cells comprise an interfollicular epidermal stem cell population in murine epidermis

    PubMed Central

    Yin, Chaoran; Zhang, Ting; Qiao, Liangjun; Du, Jia; Li, Shuang; Zhao, Hengguang; Wang, Fangfang; Huang, Qiaorong; Meng, Wentong; Zhu, Hongyan; Bu, Hong; Li, Hui; Xu, Hong; Mo, Xianming

    2014-01-01

    Normal interfollicular epidermis (IFE) homeostasis is maintained throughout the entire life by its own stem cells that self-renew and generate progeny that undergo terminal differentiation. However, the fine markers of the stem cells in interfollicular epidermis are not well defined yet. Here we found that TLR7 identified the existence of progenitors and interfollicular epidermal stem cells in murine skin. In vitro, TLR7-expressing cells comprised of two subpopulations that were competent to proliferate and exhibited distinct differentiation potentials. Three-dimensional (3D) organotypic culture and skin reconstitution assays showed that TLR7-expressing cells were able to reconstruct the interfollicular epidermis. Finally, TLR7-expressing cells maintained the intact interfollicular epidermal structures revealed in serial transplantation assays in vivo in mice. Taken together, our results suggest that TLR7-expressing cells comprise an interfollicular epidermal stem cell population. PMID:25060222

  4. TLR7-expressing cells comprise an interfollicular epidermal stem cell population in murine epidermis.

    PubMed

    Yin, Chaoran; Zhang, Ting; Qiao, Liangjun; Du, Jia; Li, Shuang; Zhao, Hengguang; Wang, Fangfang; Huang, Qiaorong; Meng, Wentong; Zhu, Hongyan; Bu, Hong; Li, Hui; Xu, Hong; Mo, Xianming

    2014-07-25

    Normal interfollicular epidermis (IFE) homeostasis is maintained throughout the entire life by its own stem cells that self-renew and generate progeny that undergo terminal differentiation. However, the fine markers of the stem cells in interfollicular epidermis are not well defined yet. Here we found that TLR7 identified the existence of progenitors and interfollicular epidermal stem cells in murine skin. In vitro, TLR7-expressing cells comprised of two subpopulations that were competent to proliferate and exhibited distinct differentiation potentials. Three-dimensional (3D) organotypic culture and skin reconstitution assays showed that TLR7-expressing cells were able to reconstruct the interfollicular epidermis. Finally, TLR7-expressing cells maintained the intact interfollicular epidermal structures revealed in serial transplantation assays in vivo in mice. Taken together, our results suggest that TLR7-expressing cells comprise an interfollicular epidermal stem cell population.

  5. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

    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.

  7. Establishment of a murine epidermal cell line suitable for in vitro and in vivo skin modelling

    PubMed Central

    2011-01-01

    Background Skin diseases are a major health problem. Some of the most severe conditions involve genetic disorders, including cancer. Several of these human diseases have been modelled in genetically modified mice, thus becoming a highly valuable preclinical tool for the treatment of these pathologies. However, development of three-dimensional models of skin using keratinocytes from normal and/or genetically modified mice has been hindered by the difficulty to subculture murine epidermal keratinocytes. Methods We have generated a murine epidermal cell line by serially passaging keratinocytes isolated from the back skin of adult mice. We have termed this cell line COCA. Cell culture is done in fully defined media and does not require feeder cells or any other coating methods. Results COCA retained its capacity to differentiate and stratify in response to increased calcium concentration in the cell culture medium for more than 75 passages. These cells, including late passage, can form epidermis-like structures in three-dimensional in vitro models with a well-preserved pattern of proliferation and differentiation. Furthermore, these cells form epidermis in grafting assays in vivo, and do not develop tumorigenic ability. Conclusions We propose that COCA constitutes a good experimental system for in vitro and in vivo skin modelling. Also, cell lines from genetically modified mice of interest in skin biology could be established using the method we have developed. COCA keratinocytes would be a suitable control, within a similar background, when studying the biological implications of these alterations. PMID:21510892

  8. The important role of epidermal triacylglycerol metabolism for maintenance of the skin permeability barrier function.

    PubMed

    Radner, Franz P W; Fischer, Judith

    2014-03-01

    Survival in a terrestrial, dry environment necessitates a permeability barrier for regulated permeation of water and electrolytes in the cornified layer of the skin (the stratum corneum) to minimize desiccation of the body. This barrier is formed during cornification and involves a cross-linking of corneocyte proteins as well as an extensive remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by various hydrolytic enzymes generates ceramides, cholesterol, and non-esterified fatty acids for the extracellular lipid lamellae in the stratum corneum. However, the important role of epidermal triacylglycerol (TAG) metabolism during formation of a functional permeability barrier in the skin was only recently discovered. Humans with mutations in the ABHD5/CGI-58 (α/β hydrolase domain containing protein 5, also known as comparative gene identification-58, CGI-58) gene suffer from a defect in TAG catabolism that causes neutral lipid storage disease with ichthyosis. In addition, mice with deficiencies in genes involved in TAG catabolism (Abhd5/Cgi-58 knock-out mice) or TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2, Dgat2 knock-out mice) also develop severe skin permeability barrier dysfunctions and die soon after birth due to increased dehydration. As a result of these defects in epidermal TAG metabolism, humans and mice lack ω-(O)-acylceramides, which leads to malformation of the cornified lipid envelope of the skin. In healthy skin, this epidermal structure provides an interface for the linkage of lamellar membranes with corneocyte proteins to maintain permeability barrier homeostasis. This review focuses on recent advances in the understanding of biochemical mechanisms involved in epidermal neutral lipid metabolism and the generation of a functional skin permeability barrier. 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

  9. Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian Schmidtea mediterranea.

    PubMed

    Bansal, Dhiru; Kulkarni, Jahnavi; Nadahalli, Kavana; Lakshmanan, Vairavan; Krishna, Srikar; Sasidharan, Vidyanand; Geo, Jini; Dilipkumar, Shilpa; Pasricha, Renu; Gulyani, Akash; Raghavan, Srikala; Palakodeti, Dasaradhi

    2017-09-01

    Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown of smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including zfp-1, are translationally regulated by SMED-PABPC2. Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration. © 2017. Published by The Company of Biologists Ltd.

  10. 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.

  11. Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

    PubMed Central

    Lacroix, Matthieu; Caramel, Julie; Goguet-Rubio, Perrine; Linares, Laetitia K.; Estrach, Soline; Hatchi, Elodie; Rodier, Geneviève; Lledo, Gwendaline; de Bettignies, Carine; Thépot, Amélie; Deraison, Céline; Chébli, Karim; Hainaut, Pierre; Dubus, Pierre; Sardet, Claude; Le Cam, Laurent

    2010-01-01

    A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways that play essential roles during normal development and tumorigenesis. We generated E4F1 conditional knockout mice to address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in the entire skin or in the basal compartment of the epidermis induces skin homeostasis defects, as evidenced by transient hyperplasia in the interfollicular epithelium and alteration of keratinocyte differentiation, followed by loss of cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant skin result, at least in part, from cell-autonomous alterations in ESC maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies. Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1–Arf–p53 pathway. PMID:21088222

  12. Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis.

    PubMed

    Lacroix, Matthieu; Caramel, Julie; Goguet-Rubio, Perrine; Linares, Laetitia K; Estrach, Soline; Hatchi, Elodie; Rodier, Geneviève; Lledo, Gwendaline; de Bettignies, Carine; Thépot, Amélie; Deraison, Céline; Chébli, Karim; Hovnanian, Alain; Hainaut, Pierre; Dubus, Pierre; Sardet, Claude; Le Cam, Laurent

    2010-12-07

    A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways that play essential roles during normal development and tumorigenesis. We generated E4F1 conditional knockout mice to address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in the entire skin or in the basal compartment of the epidermis induces skin homeostasis defects, as evidenced by transient hyperplasia in the interfollicular epithelium and alteration of keratinocyte differentiation, followed by loss of cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant skin result, at least in part, from cell-autonomous alterations in ESC maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies. Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1-Arf-p53 pathway.

  13. 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.

  14. Topical apigenin improves epidermal permeability barrier homoeostasis in normal murine skin by divergent mechanisms.

    PubMed

    Hou, Maihua; Sun, Richard; Hupe, Melanie; Kim, Peggy L; Park, Kyungho; Crumrine, Debra; Lin, Tzu-Kai; Santiago, Juan Luis; Mauro, Theodora M; Elias, Peter M; Man, Mao-Qiang

    2013-03-01

    The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In this study, we first determined whether topical apigenin positively influences permeability barrier homoeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice daily for 9 days. At the end of the treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homoeostasis after tape stripping, although basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were upregulated by apigenin. Finally, both cathelicidin-related peptide and mouse beta-defensin 3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels and impaired antimicrobial defenses, such as atopic dermatitis. © 2013 John Wiley & Sons A/S.

  15. Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells

    PubMed Central

    Foijer, Floris; DiTommaso, Tia; Donati, Giacomo; Hautaviita, Katta; Xie, Stephanie Z.; Heath, Emma; Smyth, Ian; Watt, Fiona M.; Sorger, Peter K.; Bradley, Allan

    2013-01-01

    The spindle assembly checkpoint (SAC) ensures correct chromosome segregation during mitosis by preventing aneuploidy, an event that is detrimental to the fitness and survival of normal cells but oncogenic in tumor cells. Deletion of SAC genes is incompatible with early mouse development, and RNAi-mediated depletion of SAC components in cultured cells results in rapid death. Here we describe the use of a conditional KO of mouse Mad2, an essential component of the SAC signaling cascade, as a means to selectively induce chromosome instability and aneuploidy in the epidermis of the skin. We observe that SAC inactivation is tolerated by interfollicular epidermal cells but results in depletion of hair follicle bulge stem cells. Eventually, a histologically normal epidermis develops within ∼1 mo after birth, albeit without any hair. Mad2-deficient cells in this epidermis exhibited abnormal transcription of metabolic genes, consistent with aneuploid cell state. Hair follicle bulge stem cells were completely absent, despite the continued presence of rudimentary hair follicles. These data demonstrate that different cell lineages within a single tissue respond differently to chromosome instability: some proliferating cell lineages can survive, but stem cells are highly sensitive. PMID:23382243

  16. In vivo behavior of murine epidermal cell lines derived from initiated and noninitiated skin.

    PubMed

    Conti, C J; Fries, J W; Viaje, A; Miller, D R; Morris, R; Slaga, T J

    1988-01-15

    The in vivo behavior of cell cultures derived from normal and carcinogen-treated mouse epidermis was studied by implanting the cultures in a s.c. vascularized bed protected by a silicone chamber. Cells derived from normal adult mouse epidermis as well as cells derived from tumor-promoter-treated skin were unable to grow in these systems. Conversely, cell lines derived from skin initiated with single doses of N-methyl-N'-nitro-N-nitrosoguanidine or 9,10-dimethyl-1,2-benzanthracene proliferated in these chambers, reforming an epithelial structure. The type of structure in the chambers varied, ranging from formation of almost normal epithelia to atypical invasive behavior. The variable in vivo behavior among the different cell lines may be attributed to the initiation agent, the number of passages of the cultures, random genetic events, the strain of mouse, or a combination of these factors. Most of the cell types used in this study and all the cell lines that were able to grow in these chambers were selected for resistance to Ca-induced terminal differentiation. However, resistance to terminal differentiation according to the Ca2+ switch does not always correlate with the ability to grow in the chambers, since cell lines derived from spontaneous foci of resistance failed to grow in this system. These studies showed some of the possibilities of the SC silicone chambers to study the histogenic potential of cell lines derived from carcinogen-treated epidermis. This system also appears suitable to study the complex relationship between epidermal cells and specialized (dermal) stroma.

  17. Comparison of the toxicity of sintered and unsintered indium-tin oxide particles in murine macrophage and epidermal cells.

    PubMed

    Olgun, Nicole S; Morris, Anna M; Barber, Tabatha Lynn; Stefaniak, Aleksandr B; Kashon, Michael L; Schwegler-Berry, Diane; Cummings, Kristin J; Leonard, Stephen S

    2017-09-15

    Indium-tin oxide (ITO) is used to produce flat panel displays and several other technology products. Composed of 90% indium oxide (In2O3) and 10% tin oxide (SnO2) by weight, ITO is synthesized under conditions of high heat via a process known as sintering. Indium lung disease, a recently recognized occupational illness, is characterized by pulmonary alveolar proteinosis, fibrosis, and emphysema. Murine macrophage (RAW 264.7) and epidermal (JB6) cells stably transfected with AP-1 to study tumor promoting potential, were used to differentiate between the toxicological profiles of sintered ITO (SITO) and unsintered mixture (UITO). We hypothesized that sintering would play a key role in free radical generation and cytotoxicity. Exposure of cells to both UITO and SITO caused a time and dose dependent decrease of the viability of cells. Intracellular ROS generation was inversely related to the dose of both UITO and SITO, a direct reflection of the decreased number of viable RAW 264.7 and JB6/AP-1 cells observed at higher concentrations. Electron spin resonance showed significantly increased hydroxyl radical (OH) generation in cells exposed to UITO compared to SITO. This is different from LDH release, which showed that SITO caused significantly increased damage to the cell membrane compared to UITO. Lastly, the JB6/AP-1 cell line did not show activation of the AP-1 pathway. Our results highlight both the differences in the mechanisms of cytotoxicity and the consistent adverse effects associated with UITO and SITO exposure. Published by Elsevier Inc.

  18. 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

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

    PubMed

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

    2014-08-11

    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. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Murine peptidoglycan recognition proteins PglyrpIalpha and PglyrpIbeta are encoded in the epidermal differentiation complex and are expressed in epidermal and hematopoietic tissues.

    PubMed

    Mathur, Punam; Murray, Beth; Crowell, Thomas; Gardner, Humphrey; Allaire, Normand; Hsu, Yen-Ming; Thill, Greg; Carulli, John P

    2004-06-01

    Peptidoglycan recognition proteins (PGRPs or PGLYRPs) are pattern recognition molecules that are found in insects and mammals and are critical for innate immune responses. PGRPs bind peptidoglycan, a ubiquitous component of bacterial cell walls, and are involved in killing bacteria, degrading peptidoglycan, and initiating host defense reactions. Relatively little is known about the four mammalian PGRPs. In this article, we report the sequences of mouse PglyrpIalpha and PglyrpIbeta and provide details of their expression in wild-type mouse tissues. PglyrpIalpha and PglyrpIbeta are encoded within the epidermal differentiation complex on mouse chromosome 3F. Both genes are expressed in epidermal and hematopoietic tissues. PglyrpIbeta is expressed in each of 16 tissues tested, while PglyrpIalpha expression is limited to fewer tissues, including the lung and spleen as well as several tissues of the digestive system. Both proteins are expressed in epithelial cells throughout the gut, and immunohistochemical staining shows expression in salivary glands, the squamous epithelium of the stomach, and the villi of the jejunum. Immunohistochemical staining further shows expression of both PglyrpIalpha and PglyrpIbeta in macrophages in the spleen. PglyrpIalpha is not expressed in resting RAW264.7 macrophage-like cells, but is induced by stimulation with lipopolysaccharide. PglyrpIbeta is constitutively expressed in RAW264.7 cells and is unaffected by lipopolysaccharide or peptidoglycan stimulation. Computational and experimental data suggest that these proteins are secreted. This work provides a step toward understanding the roles of PglyrpIalpha and PglyrpIbeta in host defense and chronic inflammatory conditions induced by bacteria or their components.

  1. Solution structure of murine epidermal growth factor: determination of the polypeptide backbone chain-fold by nuclear magnetic resonance and distance geometry

    SciTech Connect

    Montelione, G.T.; Wuethrich, K.; Nice, E.C.; Burgess, A.W.; Scheraga, H.A.

    1987-08-01

    The polypeptide backbone fold in the solution structure of murine epidermal growth factor has been determined by nuclear magnetic resonance spectroscopy and distance geometry calculations. The results are based on nearly complete sequence-specific resonance assignments and on 333 distance and dihedral-angle constraints; these were determined from nuclear Overhauser effect measurements, identification of hydrogen-bonded amide protons, the known locations of disulfide bonds, and backbone vicinal spin-spin coupling constants. The polypeptide chains of the protein is arranged into two distinct domains. The structures of these domains were determined independently in separate calculations and then combined to obtain an overall view of the protein. The backbone fold thus determined includes the regular backbone structure elements that were previously identified using different techniques for the analysis of the nuclear magnetic resonance data. The distance geometry calculations also provided additional details about the conformations of bends and loops and about the twists of the ..beta..-sheets.

  2. Using optical coherence tomography for the longitudinal noninvasive evaluation of epidermal thickness in a murine model of chronic skin inflammation

    PubMed Central

    Silver, Rachel; Helms, Amy; Fu, Wen; Wang, Hui; Diaconu, Doina; Loyd, Candace M.; Rollins, Andrew M.; Ward, Nicole L.

    2012-01-01

    Background Noninvasive methods are desirable for longitudinal studies examining drug efficacy and disease resolution defined as decreases in epidermal thickness in mouse models of psoriasiform skin disease. This would eliminate the need for either sacrificing animals or collecting serial skin biopsies to evaluate changes in disease progression during an individual study. Quantification of epidermal thickness using Optical Coherence Tomography (OCT) provides an alternative to traditional histology techniques. Methods Using the KC-Tie2 doxycycline-repressible psoriasiform skin disease mouse model, OCT imaging was completed on diseased back skin of adult KC-Tie2 (n=3-4) and control (n=3-4) mice, followed immediately by the surgical excision of the same region for histological analyses. Animals were then treated with doxycycline to suppress transgene expression and reverse the skin disease and additional OCT images and tissues were collected 2 and 4 weeks following. Epidermal thickness was measured using OCT and histology. Results OCT and histology both demonstrated KC-Tie2 mice had significantly thicker epidermis (~4-fold; p<0.0001) than control animals. By two weeks following gene repression, decreases in epidermal thickness were observed using both OCT and histology, and were sustained through 4 weeks. Correlation analyses between histology and OCT values at all time points and in all animals revealed high significance (R2=0.78); with correlation being highest in KC-Tie2 mice (R2=0.92) compared to control animals (R2=0.16). Conclusion Noninvasive OCT imaging provided similar values as those collected using standard histological measures in thick skin of KC-Tie2 mice but became less reliable in thinner control mouse skin, possibly reflecting limitations in resolution of OCT. Future advances in resolution of OCT may improve and allow greater accuracy of epidermal thickness measurements. PMID:22092854

  3. Possible role of different animal species in maintenance and spread of murine gammaherpesvirus 68 in the nature.

    PubMed

    Wágnerová, M; Chalupková, A; Hrabovská, Z; Ančicová, L; Mistríková, J

    2015-03-01

    Murine gammaherpesvirus 68 (MHV-68), isolated from a bank vole (Clethrionomys glareolus) in Slovakia in 1976 is a natural pathogen of wild murid rodents. This review is focused to biological properties of this pathogen, the mode of its maintenance in murid rodents as reservoir animals, mechanisms of its spread to other animals in the same biotope as well as to livestock and household animals. Potential role of ticks as vectors and the possibility of infection of humans with this virus are considered as well. All the above evidence of the virus infection of various hosts is based on serological or molecular analytical data. The presented knowledge indicates important epizootologic consequences, namely harboring and permanent maintenance of the virus in murid rodents as reservoir animals with a real possibility of spread to other animals in the same biotope. These relationships imply a cross-species virus transmission with potential serious consequences for the infected animals or humans.

  4. 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.

  5. Effects of an epidermal growth factor receptor-based cancer vaccine on wound healing and inflammation processes in murine experimental models.

    PubMed

    Fuentes, Dasha; Chacón, Lewis; Casacó, Angel; Ledón, Nuris; Fernández, Nidia; Iglesias, Arianna; Hernández, Diana R; Sánchez, Belinda; Pérez, Rolando

    2014-02-01

    Anti-epidermal growth factor receptor (EGFR) therapies have been proven clinically effective for a variety of epithelial tumours. Vaccination of mice with the extracellular domain (ECD) of autologous EGFR overcomes the tolerance to self-EGFR and has antimetastatic effect on EGFR+ tumour. Because EGF/EGFR-signalling plays an important role in the inflammation stage of wound healing, the main objective of this study was to explore the possible role of murine (m) EGFR-ECD vaccine in the croton-oil-induced ear oedema and wound healing process in mice as autologous experimental models, mimicking the possible post-surgical wound complication in patients treated with human EGFR-ECD/VSSP vaccine. Mice were intramuscularly immunised four times; biweekly with the mEGFR-ECD/VSSP/Mont. Seven days later, an 8 mm diameter, full-thickness skin wound was created on the back of each animal. Immunisation induced a strong specific humoral response against the mEGFR-ECD protein and a DTH dose-response curve but interestingly, animals treated with mEGFR-ECD/VSSP/Mont had similar inflammatory and healing speed responses compared to control ones. These data suggest that application of mEGFR-ECD/VSSP vaccine as a therapeutic approach in cancer patients could not elicit a poor healing process after surgery.

  6. Effect of Recombinant Human Epidermal Growth Factor Against Cutaneous Scar Formation in Murine Full-thickness Wound Healing

    PubMed Central

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

    2010-01-01

    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)-β1 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-β1, and mediating the formation of collagen. PMID:20358003

  7. 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.

  8. The Role of Hibiscus sabdariffa L. (Roselle) in Maintenance of Ex Vivo Murine Bone Marrow-Derived Hematopoietic Stem Cells

    PubMed Central

    Abdul Hamid, Zariyantey; Lin Lin, Winnie Hii; Abdalla, Basma Jibril; Bee Yuen, Ong; Latif, Elda Surhaida; Mohamed, Jamaludin; Rajab, Nor Fadilah; Paik Wah, Chow; 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

  9. Efficacy of 50 Hz electromagnetic fields on human epidermal stem cell transplantation seeded in collagen sponge scaffolds for wound healing in a murine model.

    PubMed

    Bai, Wen-Fang; Xu, Wei-Cheng; Zhu, Hong-Xiang; Huang, Hong; Wu, Bo; Zhang, Ming-Sheng

    2017-04-01

    To explore the possible efficacy of electromagnetic fields (EMF) for skin tissue engineering, effects of EMF exposure on epidermal stem cells (ESC) seeded in collagen sponge scaffolds for wound healing in a murine model were investigated. The wound models of a full-thickness defect established with 36 7 ∼ 8-week-old nude mice were randomly divided into three groups: a control group, an ESC-only group, and an ESC with EMF exposure group (frequency of 50 Hz, magnetic induction of 5 mT, 60 min per day for 20 days). ESC were separated from human foreskin and cultured in vitro, and then transplanted with collagen sponge scaffolds as a delivery vehicle to wounds of the ESC-only group, and ESC with EMF exposure group was exposed to EMF after ESC transplantation. Effects of EMF on morphological changes and expression of β1 integrin in regenerated skins were observed. Wound healing rates and healing times were collected to evaluate the efficacy of repairment. Results showed that human ESC were successfully transplanted to nude mice, which facilitated the formation of intact skin on nude mice. In contrast to other groups, the wound healing of ESC with EMF exposure group was the fastest (P < 0.05), the structure of regenerated skins was more mature, and it contained more continuity in the number of viable cell layers and rich hair follicles' structure. These results suggest that the use of 50 Hz EMF as a non-invasive treatment can accelerate wound healing of ESC transplantation, and restore structural integrity of regenerated skin. Bioelectromagnetics. 38:204-212,2017. © 2017 Wiley Periodicals, Inc.

  10. CD45 phosphatase is crucial for human and murine acute myeloid leukemia maintenance through its localization in lipid rafts

    PubMed Central

    Saint-Paul, Laetitia; Nguyen, Chi-Hung; Buffière, Anne; de Barros, Jean-Paul Pais; Hammann, Arlette; Landras-Guetta, Corinne; Filomenko, Rodolphe; Chrétien, Marie-Lorraine; Johnson, Pauline; Bastie, Jean-Noël; Delva, Laurent; Quéré, Ronan

    2016-01-01

    CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of signal transduction in hematopoiesis. Exploiting CD45 KO mice and lentiviral shRNA, we prove the crucial role that CD45 plays in acute myeloid leukemia (AML) development and maintenance. We discovered that CD45 does not colocalize with lipid rafts on murine and human non-transformed hematopoietic cells. Using a mouse model, we proved that CD45 positioning within lipid rafts is modified during their oncogenic transformation to AML. CD45 colocalized with lipid rafts on AML cells, which contributes to elevated GM-CSF signal intensity involved in proliferation of leukemic cells. We furthermore proved that the GM-CSF/Lyn/Stat3 pathway that contributes to growth of leukemic cells could be profoundly affected, by using a new plasma membrane disrupting agent, which rapidly delocalized CD45 away from lipid rafts. We provide evidence that this mechanism is also effective on human primary AML samples and xenograft transplantation. In conclusion, this study highlights the emerging evidence of the involvement of lipid rafts in oncogenic development of AML and the targeting of CD45 positioning among lipid rafts as a new strategy in the treatment of AML. PMID:27579617

  11. CD45 phosphatase is crucial for human and murine acute myeloid leukemia maintenance through its localization in lipid rafts.

    PubMed

    Saint-Paul, Laetitia; Nguyen, Chi-Hung; Buffière, Anne; Pais de Barros, Jean-Paul; Hammann, Arlette; Landras-Guetta, Corinne; Filomenko, Rodolphe; Chrétien, Marie-Lorraine; Johnson, Pauline; Bastie, Jean-Noël; Delva, Laurent; Quéré, Ronan

    2016-10-04

    CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of signal transduction in hematopoiesis. Exploiting CD45 KO mice and lentiviral shRNA, we prove the crucial role that CD45 plays in acute myeloid leukemia (AML) development and maintenance. We discovered that CD45 does not colocalize with lipid rafts on murine and human non-transformed hematopoietic cells. Using a mouse model, we proved that CD45 positioning within lipid rafts is modified during their oncogenic transformation to AML. CD45 colocalized with lipid rafts on AML cells, which contributes to elevated GM-CSF signal intensity involved in proliferation of leukemic cells. We furthermore proved that the GM-CSF/Lyn/Stat3 pathway that contributes to growth of leukemic cells could be profoundly affected, by using a new plasma membrane disrupting agent, which rapidly delocalized CD45 away from lipid rafts. We provide evidence that this mechanism is also effective on human primary AML samples and xenograft transplantation. In conclusion, this study highlights the emerging evidence of the involvement of lipid rafts in oncogenic development of AML and the targeting of CD45 positioning among lipid rafts as a new strategy in the treatment of AML.

  12. Side population of a murine mantle cell lymphoma model contains tumour-initiating cells responsible for lymphoma maintenance and dissemination

    PubMed Central

    Vega, Francisco; Davuluri, Yogesh; Cho-Vega, Jeong Hee; Singh, Rajesh R; Ma, Shuguang; Wang, Rui-Yu; Multani, Asha S; Drakos, Elias; Pham, Lan V; Lee, Yen-Chiu Lin; Shen, Long; Ambrus Jr, Julian; Medeiros, L Jeffrey; Ford, Richard J

    2010-01-01

    Abstract ‘Cancer stem cells’ or ‘tumour initiating cells’ in B-cell non-Hodgkin lymphomas have not been demonstrated, although some studies focused on other cancer types suggest that such populations exist and represent tumour cells resistant to therapy and involved in relapse. These cells may also represent a putative neoplastic ‘cell of origin’ in lymphomas, but there is little substantive data to support this suggestion. Using cell lines derived from a recently established murine IL-14α× c-Myc double transgenic/mantle cell lymphoma-blastoid variant model, heretofore referred to as DTG cell lines, we identified a subset of cells within the side population (SP) with features of ‘tumour-initiating cells’. These features include higher expression of ABCG2 and BCL-2, longer telomere length, greater self-renewal ability and higher in vitro clonogenic and in vivo tumorigenic capacities compared with non-SP. In addition, in vitro viability studies demonstrated that the non-SP lymphoma subpopulation has a limited lifespan in comparison with the SP fraction. Syngenic transplant studies showed that non-SP derived tumours, in comparison to the SP-derived tumours, exhibit greater necrosis/apoptosis and less systemic dissemination capability. In conclusion, our data support the interpretation that the DTG SP fraction contains a cell population highly capable of tumour maintenance and systemic dissemination and lends support to the concept that ‘tumour-initiating cells’ occur in lymphomas. PMID:19656242

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

    PubMed

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

    2014-06-01

    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.

  14. Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is overexpressed in inflammatory skin diseases and affects epidermal morphology in constitutive knockout mice and murine 3D skin models.

    PubMed

    Huth, Sebastian; Heise, Ruth; Vetter-Kauczok, Claudia S; Skazik, Claudia; Marquardt, Yvonne; Czaja, Katharina; Knüchel, Ruth; Merk, Hans F; Dahl, Edgar; Baron, Jens M

    2015-09-01

    Inter-α-trypsin inhibitors are protease inhibitors that are thought to be important regulators in various acute-phase processes. They are composed of one light chain (bikunin) and different heavy chains (ITIHs). The only function known so far of ITIHs is the covalent linkage to hyaluronan (HA). As there is virtually no knowledge on the distribution and function of ITIH proteins in skin tissue, we performed a systematic characterization of ITIH expression in healthy and diseased skin. Using GeneChip(®) Human Exon 1.0 ST expression profiling, we found that ITIH5 represents the major ITIH family member expressed in human skin. Moreover, the use of quantitative reverse transcription PCR and a customized ITIH5-specific antibody indicated that ITIH5 is predominantly produced by dermal fibroblasts. Immunohistochemical analysis revealed a clearly detectable ITIH5 protein expression in normal skin. Interestingly, ITIH5 expression was significantly up-regulated in inflammatory skin diseases. Furthermore, 3D skin models employing murine Itih5(-/-) epidermal keratinocytes and dermal fibroblasts as well as skin specimens of Itih5(-/-) mice revealed a significantly altered epidermal structure compared to wild-type controls. Hence, we can strengthen the presumption that ITIH5 may constitute a novel regulatory molecule of the human skin that could play an important role in inflammation via its interaction with HA.

  15. Epidermal Barriers

    PubMed Central

    Natsuga, Ken

    2014-01-01

    The epidermis functions as a physical barrier to the external environment and works to prevent loss of water from the skin. Numerous factors have been implicated in the formation of epidermal barriers, such as cornified envelopes, corneocytes, lipids, junctional proteins, proteases, protease inhibitors, antimicrobial peptides, and transcription factors. This review illustrates human diseases (ichthyoses) and animal models in which the epidermal barrier is disrupted or dysfunctional at steady state owing to ablation of one or more of the above factors. These diseases and animal models help us to understand the complicated mechanisms of epidermal barrier formation and give further insights on epidermal development. PMID:24692192

  16. GPR43 activation enhances psoriasis-like inflammation through epidermal upregulation of IL-6 and dual oxidase 2 signaling in a murine model.

    PubMed

    Nadeem, Ahmed; Ahmad, Sheikh F; Al-Harbi, Naif O; El-Sherbeeny, Ahmed M; Al-Harbi, Mohammed M; Almukhlafi, Talal S

    2017-05-01

    The gut is densely inhabited by commensal bacteria, which metabolize dietary fibers/undigested carbohydrates and produce short-chain fatty acids such as acetate. GPR43 is one of the receptors to sense short-chain fatty acids, and expressed in various immune and non-immune cells. Acetate/GPR43 signaling has been shown to affect various inflammatory diseases through Th17 responses and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) generation. However, no study has previously explored the effects of GPR43 activation during psoriasis-like inflammation. Therefore, this study investigated the effect of acetate/phenylacetamide (GPR43 agonists) on imiquimod induced skin inflammation in mice. Mice were administered phenylacetamide/acetate followed by assessment of skin inflammation, NOXs (NOX-2, NOX-4, dual oxidases), and Th17 related signaling. Our study showed induction of epidermal GPR43 after imiquimod treatment, i.e. psoriasis-like inflammation. Acetate administration in psoriatic mice led to further increase in skin inflammation (ear thickness/myeloperoxidase activity) with concurrent increase in Th17 immune responses and epidermal dual oxidase-2 signaling. Further, topical application of GPR43 agonist, phenylacetamide led to enhanced ear thickness with concomitant epidermal IL-6 signaling as well as dual oxidase-2 upregulation which may be responsible for increased psoriasis-like inflammation. Taken together, dual oxidase-2 and IL-6 play important roles in GPR43-mediated skin inflammation. The current study suggests that GPR43 activation in psoriatic patients may lead to aggravation of psoriatic inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Murine epidermal antigen-presenting cells in primary and secondary T-cell proliferative responses to a soluble protein antigen in vitro.

    PubMed Central

    Williams, N A; Hill, T J; Hooper, D C

    1990-01-01

    The capacity of epidermal cells (EC) to present antigen to primed and non-immune T cells was investigated using a culture system that supports antigen-specific primary and secondary proliferative responses. Although both naive and bovine serum albumin (BSA)-immune T cells reacted against BSA in the presence of either splenic or epidermal antigen-presenting cells (APC), important differences were noted in the kinetics and the magnitudes of the various responses. Most conspicuous was the relatively poor primary response supported by EC which evidently elicited very few BSA-immune T-helper cells. Despite this, the primed antigen-specific T cells recovered were phenotypically similar to those resulting from the stronger primary responses induced by spleen cells. In contrast to this disparity in the ability to prime, EC and spleen cells stimulated secondary reactions of comparable magnitude. We therefore consider that, in comparison with splenic APC, EC may require some additional stimulus to acquire the capacity to prime. PMID:2148541

  18. Epidermal growth factor receptor derived peptide vaccination to prevent lung adenocarcinoma formation: An in vivo study in a murine model of EGFR mutant lung cancer.

    PubMed

    Ebben, Johnathan D; Lubet, Ronald A; Gad, Ekram; Disis, Mary L; You, Ming

    2016-11-01

    The ability to prevent disease is the holy grail of medicine. For decades, efforts have been made to extend the successes seen with vaccination against infectious diseases to cancer. In some instances, preventive vaccination against viruses (prototypically HPV) has successfully prevented tumorigenesis and will make a major impact on public health in the decades to come. However, the majority of cancers that arise are a result of genetic mutation within the host, or non-viral environmental exposures. We present compelling evidence that vaccination against an overexpressed self-tumor oncoprotein has the potential to prevent tumor development. Vaccination against the Epidermal Growth Factor Receptor (EGFR) using a multipeptide vaccine in a preventive setting decreased EGFR-driven lung carcinogenesis by 76.4% in a mouse model of EGFR-driven lung cancer. We also demonstrate that anti-EGFR vaccination primes the development of a robust immune response in vivo. This study provides proof of concept for the first time that targeting tumor drivers in a preventive setting in lung cancer using peptide vaccination can inhibit tumorigenesis and may provide useful clinical insights into the development of strategies to vaccinate against EGFR in populations where EGFR-mutant disease is highly prevalent. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  19. 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.

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

    PubMed

    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(+)). 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(+) 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(+/+) 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(+/+) 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.

  1. Modulation of hepatic acute phase gene expression by epidermal growth factor and Src protein tyrosine kinases in murine and human hepatic cells.

    PubMed

    Wang, Y; Ripperger, J; Fey, G H; Samols, D; Kordula, T; Wetzler, M; Van Etten, R A; Baumann, H

    1999-09-01

    As part of systemic inflammatory reactions, interleukin 6 (IL-6) induces acute phase protein (APP) genes through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Epidermal growth factor (EGF), which contributes to the regenerative process after liver injury and also activates STATs, does not induce but attenuates IL-6-stimulated expression of several APP genes in primary mouse hepatocytes. The APP-modifying action of EGF receptor (EGFR) was characterized in HepG2 cells. Although EGF less effectively engages STAT proteins in these cells, it reduces expression of fibrinogen and haptoglobin, but stimulates production of alpha(1)-antichymotrypsin and induces transcription through the alpha(1)-antichymotrypsin and C-reactive protein promoter. The stimulatory EGFR signal is insensitive to inhibition of JAKs and appears to involve Src kinases and STAT proteins as shown by inhibition through overexpression of C-terminal Src kinase (Csk) and transdominant negative STAT3, respectively. A mediator role of Src is supported by the ability of c-Src and v-Src to activate STATs and induce transcription through APP promoters. Src kinases have been observed in association with the IL-6 receptor; however, inhibition of Src kinases by Csk enhances IL-6-induced transcription. The Csk effect is attributed to prevention of Src kinases from phosphorylating gp130 at the docking site for the signal-moderating protein tyrosine phosphatase SHP-2. The inhibitory EGFR signal on APP expression correlates with the activation of Erk1 and Erk2. The study shows a dual signaling function for EGFR and suggests that the ratio of receptor-activated STATs and Erks influence the level of stimulated or inhibited expression of individual APPs.

  2. 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.

  3. Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) Signaling Is Essential for Murine Pancreatitis-Associated Tissue Regeneration.

    PubMed

    Wodziak, Dariusz; Dong, Aiwen; Basin, Michael F; Lowe, Anson W

    2016-01-01

    A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model. EGFR signaling and cell proliferation were examined in the context of the AGR2-/- null mouse or with the EGFR-specific tyrosine kinase inhibitor, AG1478. In addition, the Hippo signaling coactivator YAP1 was evaluated in the context of AGR2 expression during pancreatitis. Pancreatitis-induced AGR2 expression enabled EGFR translocation to the plasma membrane, the initiation of cell signaling, and cell proliferation. EGFR signaling and tissue regeneration were partially inhibited by the tyrosine kinase inhibitor AG1478, but absent in the AGR2-/- null mouse. AG1478-treated and AGR2-/- null mice with pancreatitis died whereas all wild-type controls recovered. YAP1 activation was also dependent on pancreatitis-induced AGR2 expression. AGR2-induced EGFR signaling was essential for tissue regeneration and recovery from pancreatitis. The results establish tissue regeneration as a major function of AGR2-induced EGFR signaling in adult higher vertebrates. Enhanced AGR2 expression and EGFR signaling are also universally present in human pancreatic cancer, which support a linkage between tissue injury, regeneration, and cancer pathogenesis.

  4. Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) Signaling Is Essential for Murine Pancreatitis-Associated Tissue Regeneration

    PubMed Central

    Wodziak, Dariusz; Dong, Aiwen; Basin, Michael F.; Lowe, Anson W.

    2016-01-01

    A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model. EGFR signaling and cell proliferation were examined in the context of the AGR2-/- null mouse or with the EGFR-specific tyrosine kinase inhibitor, AG1478. In addition, the Hippo signaling coactivator YAP1 was evaluated in the context of AGR2 expression during pancreatitis. Pancreatitis-induced AGR2 expression enabled EGFR translocation to the plasma membrane, the initiation of cell signaling, and cell proliferation. EGFR signaling and tissue regeneration were partially inhibited by the tyrosine kinase inhibitor AG1478, but absent in the AGR2-/- null mouse. AG1478-treated and AGR2-/- null mice with pancreatitis died whereas all wild-type controls recovered. YAP1 activation was also dependent on pancreatitis-induced AGR2 expression. AGR2-induced EGFR signaling was essential for tissue regeneration and recovery from pancreatitis. The results establish tissue regeneration as a major function of AGR2-induced EGFR signaling in adult higher vertebrates. Enhanced AGR2 expression and EGFR signaling are also universally present in human pancreatic cancer, which support a linkage between tissue injury, regeneration, and cancer pathogenesis. PMID:27764193

  5. Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema.

    PubMed

    Voss, Meike; Wolf, Lisa; Kamyschnikow, Andreas; Wonnenberg, Bodo; Honecker, Anja; Herr, Christian; Lepper, Philipp M; Wegmann, Michael; Menger, Michael D; Bals, Robert; Beisswenger, Christoph

    2015-07-15

    Smoking is the main risk factor for the development of the chronic obstructive pulmonary disease (COPD) in Western countries. Recent studies suggest that IL-17A and Th17 cells play a role in the pathogenesis of COPD. We used a murine model of chronic cigarette smoke (CS) exposure to explore the contribution of IL-17A to CS-induced lung damage and loss of pulmonary function. Histology and morphometry showed that IL-17A deficiency spontaneously resulted in a loss of lung structure under basal conditions. Even though inflammatory markers [IL-1β and granulocyte colony-stimulating factor (G-CSF)] were decreased in IL-17A-deficient mice (IL-17A(-/-)) exposed to CS compared with wild-type (WT) mice, IL-17A(-/-) mice were per se not protected from CS-induced emphysematous disease. Assessment of pulmonary function showed that IL-17A(-/-) mice were partially protected from CS-induced changes in total lung capacity. However, the respiratory elastance decreased and respiratory compliance increased in IL-17A(-/-) mice after exposure to CS. Morphometry revealed destruction of lung tissue in CS-exposed IL-17A(-/-) mice similar to WT mice. The expression of elastin was decreased in air-exposed IL-17A(-/-) mice and in CS-exposed WT and IL-17A(-/-) mice. Thus, in the present model of sterile CS-exposure, IL-17A contributes to normal lung homeostasis and does not mediate CS-induced loss of lung structure and pulmonary function.

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

    PubMed Central

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

    2010-01-01

    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-1β, IL-6, IL-12, and TNF-α) 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

  7. Investigation of the role of endosomal Toll-like receptors in murine collagen-induced arthritis reveals a potential role for TLR7 in disease maintenance

    PubMed Central

    2012-01-01

    Introduction Endosomal toll-like receptors (TLRs) have recently emerged as potential contributors to the inflammation observed in human and rodent models of rheumatoid arthritis (RA). This study aims to evaluate the role of endosomal TLRs and in particular TLR7 in the murine collagen induced arthritis (CIA) model. Methods CIA was induced by injection of collagen in complete Freund's adjuvant. To investigate the effect of endosomal TLRs in the CIA model, mianserin was administered daily from the day of disease onset. The specific role of TLR7 was examined by inducing CIA in TLR7-deficient mice. Disease progression was assessed by measuring clinical score, paw swelling, serum anti-collagen antibodies histological parameters, cytokine production and the percentage of T regulatory (Treg) cells. Results Therapeutic administration of mianserin to arthritic animals demonstrated a highly protective effect on paw swelling and joint destruction. TLR7-/- mice developed a mild arthritis, where the clinical score and paw swelling were significantly compromised in comparison to the control group. The amelioration of arthritis by mianserin and TLR7 deficiency both corresponded with a reduction in IL-17 responses, histological and clinical scores, and paw swelling. Conclusions These data highlight the potential role for endosomal TLRs in the maintenance of inflammation in RA and support the concept of a role for TLR7 in experimental arthritis models. This study also illustrates the potential benefit that may be afforded by therapeutically inhibiting the endosomal TLRs in RA. PMID:22691272

  8. Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes.

    PubMed

    Aoki, Hitomi; Yamada, Yasuhiro; Hara, Akira; Kunisada, Takahiro

    2009-08-01

    Unlike the thoroughly investigated melanocyte population in the hair follicle of the epidermis, the growth and differentiation requirements of the melanocytes in the eye, harderian gland and inner ear - the so-called non-cutaneous melanocytes - remain unclear. In this study, we investigated the in vitro and in vivo effects of the factors that regulate melanocyte development on the stem cells or the precursors of these non-cutaneous melanocytes. In general, a reduction in KIT receptor tyrosine kinase signaling leads to disordered melanocyte development. However, melanocytes in the eye, ear and harderian gland were revealed to be less sensitive to KIT signaling than cutaneous melanocytes. Instead, melanocytes in the eye and harderian gland were stimulated more effectively by endothelin 3 (ET3) or hepatocyte growth factor (HGF) signals than by KIT signaling, and the precursors of these melanocytes expressed the lowest amount of KIT. The growth and differentiation of these non-cutaneous melanocytes were specifically inhibited by antagonists for ET3 and HGF. In transgenic mice induced to express ET3 or HGF in their skin and epithelial tissues from human cytokeratin 14 promoters, the survival and differentiation of non-cutaneous and dermal melanocytes, but not epidermal melanocytes, were enhanced, apparently irrespective of KIT signaling. These results provide a molecular basis for the clear discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes, a difference that might be important in the pathogenesis of melanocyte-related diseases and melanomas.

  9. Epidermal lipids.

    PubMed

    Wertz, P W

    1992-06-01

    Epidermal lipids play important roles in cell structure, in control of growth and differentiation, in determining cohesion and desquamation, and in formation and function of a permeability barrier. Knowledge of the structures and composition of the epidermal lipids is important for understanding these functions. The lipids present in epidermis include phospholipids, monohexosylceramides, ceramides, cholesterol, cholesterol esters, cholesterol sulfate, triglycerides, and fatty acids. The phospholipids are major structural components of the plasma membranes and membranous organelles in the viable and differentiating keratinocytes. In addition, phospholipids serve in several transmembranal signaling processes and as a reservoir for arachidonic acid, the precursor of the eicosanoids. Monohexosylceramides are thought to function in the assembly of lamellar bodies, and in the final stage of differentiation are converted to a structurally heterogenous mixture of ceramides in the intercellular space of the stratum corneum and to a unique ceramide covalently attached to the corneocyte surface. The mixture of lipids in the stratum corneum, composed principally of ceramides, cholesterol, cholesterol esters, and fatty acids, prevents desiccation and limits the penetration of a variety of noxious environmental agents. The stratum corneum lipids represent a major product of epidermal differentiation, and free sphingosine liberated from ceramides in this terminally differentiated compartment may provide a feedback mechanism for the regulation of the differentiation process.

  10. Reduced trisialoganglioside synthesis in chemically but not mos-transformed mouse epidermal cells

    SciTech Connect

    Srinivas, L.; Colburn, N.H.

    1984-04-01

    A specific decrease in the net de novo synthesis ((1-14C)-glucosamine incorporation) of cell surface trisialoganglioside (GT) occurs in preneoplastic mouse JB6 epidermal cells in response to tumor-promoting phorbol esters, mezerein, or epidermal growth factor, all of which promote neoplastic transformation in JB6 cells, but not in response to the bladder promoter sodium cyclamate, a nonpromoter in JB6 cells. The ganglioside showing elevated synthesis after mezerein or epidermal growth factor exposure is monosialoganglioside 1, whereas disialoganglioside 1b synthesis is elevated after phorbol ester exposure. Primary mouse epidermal cells and putatively initiated epidermal cell lines selected for their resistance to induction of terminal differentiation by high calcium are resistant to promotion of anchorage-independent transformation by 2-week exposure to 12-O-tetradecanoylphorbol-13-acetate. In both cell types, little or no decrease in GT synthesis occurs in response to short-term 12-O-tetradecanoylphorbol-13-acetate exposure, thus extending further our previous observation that this GT response is restricted to promotable cells. A decreased synthesis of GT also occurs consistently in cell lines transformed by 12-O-tetradecanoylphorbol-13-acetate or N-methyl-N-nitro-nitrosoguanidine as compared with their nontransformed counterparts but not in cell lines transformed by a cloned integrated murine sarcoma provirus containing the oncogenic sequence v-mos. Thus, reduced cell surface GT synthesis may be important both in the induction and in the maintenance of the chemically transformed but not viral oncogene mos-transformed phenotype in mouse epidermal cells.

  11. The acute effects of light on murine sleep during the dark phase: importance of melanopsin for maintenance of light-induced sleep.

    PubMed

    Muindi, Fanuel; Zeitzer, Jamie M; Colas, Damien; Heller, H Craig

    2013-06-01

    Light exerts a direct effect on sleep and wakefulness in nocturnal and diurnal animals, with a light pulse during the dark phase suppressing locomotor activity and promoting sleep in the former. In the present study, we investigated this direct effect of light on various sleep parameters by exposing mice to a broad range of illuminances (0.2-200 μW/cm(2) ; equivalent to 1-1000 lux) for 1 h during the dark phase (zeitgeber time 13-14). Fitting the data with a three-parameter log model indicated that ~0.1 μW/cm(2) can generate half the sleep response observed at 200 μW/cm(2). We observed decreases in total sleep time during the 1 h following the end of the light pulse. Light reduced the latency to sleep from ~30 min in darkness (baseline) to ~10 min at the highest intensity, although this effect was invariant across the light intensities used. We then assessed the role of melanopsin during the rapid transition from wakefulness to sleep at the onset of a light pulse and the maintenance of sleep with a 6-h 20 μW/cm(2) light pulse. Even though the melanopsin knockout mice had robust induction of sleep (~35 min) during the first hour of the pulse, it was not maintained. Total sleep decreased by almost 65% by the third hour in comparison with the first hour of the pulse in mice lacking melanopsin, whereas only an 8% decrease was observed in wild-type mice. Collectively, our findings highlight the selective effects of light on murine sleep, and suggest that melanopsin-based photoreception is primarily involved in sustaining light-induced sleep.

  12. 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 Central

    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

  13. Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2-Positive Metastatic Bladder Cancer.

    PubMed

    Powles, Thomas; Huddart, Robert A; Elliott, Tony; Sarker, Shah-Jalal; Ackerman, Charlotte; Jones, Robert; Hussain, Syed; Crabb, Simon; Jagdev, Satinder; Chester, John; Hilman, Serena; Beresford, Mark; Macdonald, Graham; Santhanam, Sundar; Frew, John A; Stockdale, Andrew; Hughes, Simon; Berney, Daniel; Chowdhury, Simon

    2017-01-01

    Purpose To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2-positive metastatic urothelial bladder cancer (UBC). Methods Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS). Results Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each). Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.

  14. 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

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

    2015-01-16

    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.

  15. A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.

    PubMed

    Rodriguez, Pedro C; Popa, Xitllaly; Martínez, Odeth; Mendoza, Silvia; Santiesteban, Eduardo; Crespo, Tatiana; Amador, Rosa M; Fleytas, Ricardo; Acosta, Soraida C; Otero, Yanine; Romero, Gala N; de la Torre, Ana; Cala, Mireysi; Arzuaga, Lina; Vello, Loisel; Reyes, Delmairis; Futiel, Niurka; Sabates, Teresa; Catala, Mauricio; Flores, Yoanna I; Garcia, Beatriz; Viada, Carmen; Lorenzo-Luaces, Patricia; Marrero, Maria A; Alonso, Liuba; Parra, Jenelin; Aguilera, Nadia; Pomares, Yaisel; Sierra, Patricia; Rodríguez, Gryssell; Mazorra, Zaima; Lage, Agustin; Crombet, Tania; Neninger, Elia

    2016-08-01

    EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Epidermal Vascular Endothelial Growth Factor Production Is Required for Permeability Barrier Homeostasis, Dermal Angiogenesis, and the Development of Epidermal Hyperplasia

    PubMed Central

    Elias, Peter M.; Arbiser, Jack; Brown, Barbara E.; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R.

    2008-01-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf−/− mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis. PMID:18688025

  17. Biochemistry of epidermal stem cells☆

    PubMed Central

    Eckert, Richard L.; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan C.; Boucher, Shayne E.; Bickenbach, Jackie R.; Kerr, Candace

    2014-01-01

    Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. PMID:22820019

  18. Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis.

    PubMed

    Elias, Peter M; Arbiser, Jack; Brown, Barbara E; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R

    2008-09-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

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

    PubMed

    Pikuła, Michał; Trzonkowski, Piotr

    2009-10-15

    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.

  20. Immunohistochemical analyses point to epidermal origin of human Merkel cells.

    PubMed

    Tilling, Thomas; Wladykowski, Ewa; Failla, Antonio Virgilio; Houdek, Pia; Brandner, Johanna M; Moll, Ingrid

    2014-04-01

    Merkel cells, the neurosecretory cells of skin, are essential for light-touch responses and may probably fulfill additional functions. Whether these cells derive from an epidermal or a neural lineage has been a matter of dispute for a long time. In mice, recent studies have clearly demonstrated an epidermal origin of Merkel cells. Given the differences in Merkel cell distribution between human and murine skin, it is, however, unclear whether the same holds true for human Merkel cells. We therefore attempted to gain insight into the human Merkel cell lineage by co-immunodetection of the Merkel cell marker protein cytokeratin 20 (CK20) with various proteins known to be expressed either in epidermal or in neural stem cells of the skin. Neither Sox10 nor Pax3, both established markers of the neural crest lineage, exhibited any cell co-labeling with CK20. By contrast, β1 integrin, known to be enriched in epidermal stem cells, was found in nearly 70 % of interfollicular epidermal and 25 % of follicular Merkel cells. Moreover, LRIG1, also enriched in epidermal stem cells, displayed significant co-immunolabeling with CK20 as well (approximately 20 % in the interfollicular epidermis and 7 % in the hair follicle, respectively). Further epidermal markers were detected in sporadic Merkel cells. Cells co-expressing CK20 with epidermal markers may represent a transitory state between stem cells and differentiated cells. β1 integrin is probably also synthesized by a large subset of mature Merkel cells. Summarizing, our data suggest that human Merkel cells may originate from epidermal rather than neural progenitors.

  1. Epidermal surface lipids.

    PubMed

    Pappas, Apostolos

    2009-03-01

    A layer of lipids, which are of both sebaceous and keratinocyte origin, covers the surface of the skin. The apparent composition of surface lipids varies depending on the selected method of sampling. Lipids produced by the epidermal cells are an insignificant fraction of the total extractable surface lipid on areas rich in sebaceous glands. Due to the holocrine activity of the sebaceous gland, its product of secretion (sebum) is eventually released to the surface of the skin and coats the fur as well. Lipids of epidermal origin fill the spaces between the cells, like mortar or cement. The sebaceous lipids are primarily non polar lipids as triglycerides, wax esters and squalene, while epidermal lipids are a mixture of ceramides, free fatty acids and cholesterol. The composition of the sebaceous lipids is unique and intriguing and elevated sebum excretion is a major factor involved in the pathophysiology of acne. Recent studies have elucidated the roles that epidermal surface lipids have on normal skin functions and acne.

  2. Epidermal surface lipids

    PubMed Central

    2009-01-01

    A layer of lipids, which are of both sebaceous and keratinocyte origin, covers the surface of the skin. The apparent composition of surface lipids varies depending on the selected method of sampling. Lipids produced by the epidermal cells are an insignificant fraction of the total extractable surface lipid on areas rich in sebaceous glands. Due to the holocrine activity of the sebaceous gland, its product of secretion (sebum) is eventually released to the surface of the skin and coats the fur as well. Lipids of epidermal origin fill the spaces between the cells, like mortar or cement. The sebaceous lipids are primarily non polar lipids as triglycerides, wax esters and squalene, while epidermal lipids are a mixture of ceramides, free fatty acids and cholesterol. The composition of the sebaceous lipids is unique and intriguing and elevated sebum excretion is a major factor involved in the pathophysiology of acne. Recent studies have elucidated the roles that epidermal surface lipids have on normal skin functions and acne. PMID:20224687

  3. 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

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

    PubMed

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

    2014-12-01

    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.

  5. 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

  6. Lineage Analysis of Epidermal Stem Cells

    PubMed Central

    Alcolea, Maria P.; Jones, Philip H.

    2014-01-01

    Lineage tracing involves labeling cells to track their subsequent behavior within the normal tissue environment. The advent of genetic lineage tracing and cell proliferation assays, together with high resolution three-dimensional (3D) imaging and quantitative methods to infer cell behavior from lineage-tracing data, has transformed our understanding of murine epidermal stem and progenitor cells. Here, we review recent insights that reveal how a progenitor cell population maintains interfollicular epidermis, whereas stem cells, quiescent under homeostatic conditions, are mobilized in response to wounding. We discuss progress in understanding how the various stem cell populations of the hair follicle sustain this complex and highly dynamic structure, and recent analysis of stem cells in sweat and sebaceous glands. The extent to which insights from mouse studies can be applied to human epidermis is also considered. PMID:24384814

  7. Glucosylceramides stimulate mitogenesis in aged murine epidermis.

    PubMed

    Marchell, N L; Uchida, Y; Brown, B E; Elias, P M; Holleran, W M

    1998-04-01

    Glucosylceramides (GlcCer) and ceramides (Cer) appear to have opposite effects on epidermal growth and differentiation. Whereas Cer inhibit mitosis and induce terminal differentiation and apoptosis in cultured keratinocytes, GlcCer is mitogenic in young murine epidermis. Using a recently described murine model of chronologic senescence we explored whether GlcCer is mitogenic in aged epidermis. Epidermal GlcCer content increases following topical applications of either conduritol-B epoxide (CBE), an inhibitor of GlcCer hydrolysis, or exogenous GlcCer in a penetration-enhancing vehicle. During chronologic aging in the hairless mouse, baseline epidermal DNA synthesis rates remain normal until 18 mo, but decline significantly at 24 mo. Topical CBE stimulates a 1.5- to 1.9-fold increase in epidermal DNA synthesis in all age groups (i.e., 1-2, 18, and 24 mo). Although the CBE induced increase in [3H]thymidine incorporation in 24 mo old animals is significant (p < 0.01), it is not sufficient to reach the absolute levels reached in similarly treated, younger mouse epidermis. Moreover, topical GlcCer induced mitogenesis is both dose dependent and hexose specific in young (1-2 mo old) animals, and remains effective in aged (< or = 24 mo old) animals. Furthermore, the CBE induced increase in DNA synthesis in aged epidermis is sufficient to produce epidermal hyperplasia. Finally, although an increased GlcCer:Cer ratio can alter stratum corneum barrier function and membrane structure, neither stratum corneum function nor extracellular membrane structure change under these experimental conditions, and therefore the mitogenic effects of increased epidermal GlcCer cannot be attributed to effects on the stratum corneum. These results show that: (i) elevations in endogenous GlcCer are mitogenic for aged as well as young murine epidermis; (ii) topical GlcCer is also mitogenic when delivered in an enhancing vehicle; and (iii) despite the putative importance of epidermal DNA synthesis

  8. Testosterone perturbs epidermal permeability barrier homeostasis.

    PubMed

    Kao, J S; Garg, A; Mao-Qiang, M; Crumrine, D; Ghadially, R; Feingold, K R; Elias, P M

    2001-03-01

    Although there are no known gender-related differences in permeability barrier function in adults, estrogens accelerate whereas testosterone retards barrier development in fetal skin, and male fetuses demonstrate slower barrier development than female littermates. Moreover, prenatal administration of the androgen receptor antagonist, flutamide, equalizes developmental rates in male and female fetuses. Therefore, we evaluated the effects of changes in testosterone on barrier homeostasis in adult murine and human skin. Hypogonadal mice (whether by castration or by treatment with systemic flutamide) displayed significantly faster barrier recovery at 3, 6, and 12 h than did controls, and testosterone replacement slowed barrier recovery in castrated mice. Moreover, testosterone directly effects the skin, as topical flutamide also accelerated barrier recovery in normal male mice. These findings appear to be of physiologic significance, since prepubertal male mice (age 5 wk) displayed accelerated barrier recovery in comparison with adult postpubertal (11 wk) males. These studies also appear to be relevant for humans, as a hypopituitary human subject demonstrated repeated changes in barrier recovery in parallel with peaks and nadirs in serum testosterone levels during intermittent testosterone replacement. Mechanistic studies showed that differences in epidermal lipid synthesis do not account for the testosterone-induced functional alterations. Instead, epidermal lamellar body (LB) formation and secretion both decrease, resulting in decreased extracellular lamellar bilayers in testosterone-replete animals. These studies demonstrate that fluctuations in testosterone modulate barrier function, and that testosterone repletion can have negative consequences for permeability barrier homeostasis.

  9. Ontogeny and function of murine epidermal Langerhans cells.

    PubMed

    Kaplan, Daniel H

    2017-09-19

    Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.

  10. [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.

  11. Markers of Epidermal Stem Cell Subpopulations in Adult Mammalian Skin

    PubMed Central

    Kretzschmar, Kai; Watt, Fiona M.

    2014-01-01

    The epidermis is the outermost layer of mammalian skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. As in other epithelia, adult stem cells within the epidermis maintain tissue homeostasis and contribute to repair of tissue damage. The bulge of hair follicles, where DNA-label-retaining cells reside, was traditionally regarded as the sole epidermal stem cell compartment. However, in recent years multiple stem cell populations have been identified. In this review, we discuss the different stem cell compartments of adult murine and human epidermis, the markers that they express, and the assays that are used to characterize epidermal stem cell properties. PMID:24993676

  12. 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

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

    PubMed Central

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

    2014-01-01

    Calcium-mediated signals play important roles in epidermal barrier formation, skin homeostasis, 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

  14. Epidermal Polarity Genes in Health and Disease

    PubMed Central

    Tellkamp, Frederik; Vorhagen, Susanne; Niessen, Carien M.

    2014-01-01

    The epidermis of the skin is a highly polarized, metabolic tissue with important innate immune functions. The polarity of the epidermis is, for example, reflected in controlled changes in cell shape that accompany differentiation, oriented cell division, and the planar orientation of hair follicles and cilia. The establishment and maintenance of polarity is organized by a diverse set of polarity proteins that include transmembrane adhesion proteins, cytoskeletal scaffold proteins, and kinases. Although polarity proteins have been extensively studied in cell culture and in vivo in simple epithelia of lower organisms, their role in mammalian tissue biology is only slowly evolving. This article will address the importance of polarizing processes and their molecular regulators in epidermal morphogenesis and homeostasis and discuss how alterations in polarity may contribute to skin disease. PMID:25452423

  15. Commonly Employed African Neonatal Skin Care Products Compromise Epidermal Function in Mice.

    PubMed

    Man, Mao-Qiang; Sun, Richard; Man, George; Lee, Dale; Hill, Zelee; Elias, Peter M

    2016-09-01

    Neonatal mortality is much higher in the developing world than in developed countries. Infections are a major cause of neonatal death, particularly in preterm infants, in whom defective epidermal permeability barrier function facilitates transcutaneous pathogen invasion. The objective was to determine whether neonatal skin care products commonly used in Africa benefit or compromise epidermal functions in murine skin. After twice-daily treatment of 6- to 8-week-old hairless mice with each skin care product for 3 days, epidermal permeability barrier function, skin surface pH, stratum corneum hydration, and barrier recovery were measured using a multiprobe adapter system physiology monitor. For products showing some benefits in these initial tests, the epidermal permeability barrier homeostasis was assessed 1 and 5 hours after a single application to acutely disrupted skin. All of the skin care products compromised basal permeability barrier function and barrier repair kinetics. Moreover, after 3 days of treatment, most of the products also reduced stratum corneum hydration while elevating skin surface pH to abnormal levels. Some neonatal skin care products that are widely used in Africa perturb important epidermal functions, including permeability barrier homeostasis in mice. Should these products have similar effects on newborn human skin, they could cause a defective epidermal permeability barrier, which can increase body fluid loss, impair thermoregulation, and contribute to the high rates of neonatal morbidity and mortality seen in Africa. Accordingly, alternative products that enhance permeability barrier function should be identified, particularly for use in preterm infants. © 2016 Wiley Periodicals, Inc.

  16. 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.

  17. Polychlorinated Biphenyls Disrupt Hepatic Epidermal Growth Factor Receptor Signaling.

    PubMed

    Hardesty, Josiah E; Wahlang, Banrida; Falkner, K Cameron; Clair, Heather B; Clark, Barbara J; Ceresa, Brian P; Prough, Russell A; Cave, Matthew C

    2016-07-26

    1. Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that disrupt hepatic xenobiotic and intermediary metabolism, leading to metabolic syndrome and nonalcoholic steatohepatitis (NASH). 2. Since phenobarbital indirectly activates Constitutive Androstane Receptor (CAR) by antagonizing growth factor binding to the epidermal growth factor receptor (EGFR), we hypothesised that PCBs may also diminish EGFR signaling. 3. The effects of the PCB mixture Aroclor 1260 on the protein phosphorylation cascade triggered by EGFR activation were determined in murine (in vitro and in vivo) and human models (in vitro). EGFR tyrosine residue phosphorylation was decreased by PCBs in all models tested. 4. The IC50 values for Aroclor 1260 concentrations that decreased Y1173 phosphorylation of EGFR were similar in murine AML-12 and human HepG2 cells (∼2-4 μg/mL). Both dioxin and non-dioxin-like PCB congeners decreased EGFR phosphorylation in cell culture. 5. PCB treatment reduced phosphorylation of downstream EGFR effectors including Akt and mTOR, as well as other phosphoprotein targets including STAT3 and c-RAF in vivo. 6. PCBs diminish EGFR signaling in human and murine hepatocyte models and may dysregulate critical phosphoprotein regulators of energy metabolism and nutrition, providing a new mechanism of action in environmental diseases.

  18. Epidermal activity in annular dermatophytosis.

    PubMed

    Berk, S H; Penneys, N S; Weinstein, G D

    1976-04-01

    In five patients with annular tinea corporis, the tritated thymidine labeling indexes were determined in the rim, center, and intermediate areas of the lesion and compared with normal skin. Labeling indexes at the rim were much higher than those of normal skin (mean, 4.2 times). Labeling indexes elsewhere in the lesion were not significantly different from those of normal skin. Histologic examination showed epidermal thickening in all areas of the lesion as compared with normal skin. This study suggests that there is an increased epidermal turnover at the rim of annular dermatophytosis that may be important in the pathophysiology and morphogenesis of such lesions.

  19. 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

  20. The Histone Methyltransferase Ash1l is Required for Epidermal Homeostasis in Mice

    PubMed Central

    Li, Gang; Ye, Zhisheng; Shi, Cheng; Sun, Ling; Han, Min; Zhuang, Yuan; Xu, Tian; Zhao, Shimin; Wu, Xiaohui

    2017-01-01

    Epidermal homeostasis under normal and healing conditions are critical for the physical and functional maintenance of the skin barrier. It requires a proper balance between keratinocyte proliferation and differentiation under genetic and epigenetic regulations. Here we show that mice carrying a hypomorphic mutation of the histone methyltransferase Ash1l [(absent, small, or homeotic)-like (Drosophila)] develop epidermal hyperplasia and impaired epidermal stratification upon aging. In adult mutants, loss of Ash1l leads to more proliferative keratinocytes in disturbed differentiation stages. After wounding, Ash1l mutation leads to delayed re-epithlialization but increased keratinocyte proliferation at the wound edge. Elevated c-Myc expression could be observed in both aged and wounded mutant tissues. Taken together, these observations revealed an important role of the epigenetic regulator Ash1l in epidermal homeostasis. PMID:28374742

  1. DAPK interacts with Patronin and the microtubule cytoskeleton in epidermal development and wound repair

    PubMed Central

    Chuang, Marian; Hsiao, Tiffany I; Tong, Amy; Xu, Suhong; Chisholm, Andrew D

    2016-01-01

    Epidermal barrier epithelia form a first line of defense against the environment, protecting animals against infection and repairing physical damage. In C. elegans, death-associated protein kinase (DAPK-1) regulates epidermal morphogenesis, innate immunity and wound repair. Combining genetic suppressor screens and pharmacological tests, we find that DAPK-1 maintains epidermal tissue integrity through regulation of the microtubule (MT) cytoskeleton. dapk-1 epidermal phenotypes are suppressed by treatment with microtubule-destabilizing drugs and mimicked or enhanced by microtubule-stabilizing drugs. Loss of function in ptrn-1, the C. elegans member of the Patronin/Nezha/CAMSAP family of MT minus-end binding proteins, suppresses dapk-1 epidermal and innate immunity phenotypes. Over-expression of the MT-binding CKK domain of PTRN-1 triggers epidermal and immunity defects resembling those of dapk-1 mutants, and PTRN-1 localization is regulated by DAPK-1. DAPK-1 and PTRN-1 physically interact in co-immunoprecipitation experiments, and DAPK-1 itself undergoes MT-dependent transport. Our results uncover an unexpected interdependence of DAPK-1 and the microtubule cytoskeleton in maintenance of epidermal integrity. DOI: http://dx.doi.org/10.7554/eLife.15833.001 PMID:27661253

  2. DAPK interacts with Patronin and the microtubule cytoskeleton in epidermal development and wound repair.

    PubMed

    Chuang, Marian; Hsiao, Tiffany I; Tong, Amy; Xu, Suhong; Chisholm, Andrew D

    2016-09-23

    Epidermal barrier epithelia form a first line of defense against the environment, protecting animals against infection and repairing physical damage. In C. elegans, death-associated protein kinase (DAPK-1) regulates epidermal morphogenesis, innate immunity and wound repair. Combining genetic suppressor screens and pharmacological tests, we find that DAPK-1 maintains epidermal tissue integrity through regulation of the microtubule (MT) cytoskeleton. dapk-1 epidermal phenotypes are suppressed by treatment with microtubule-destabilizing drugs and mimicked or enhanced by microtubule-stabilizing drugs. Loss of function in ptrn-1, the C. elegans member of the Patronin/Nezha/CAMSAP family of MT minus-end binding proteins, suppresses dapk-1 epidermal and innate immunity phenotypes. Over-expression of the MT-binding CKK domain of PTRN-1 triggers epidermal and immunity defects resembling those of dapk-1 mutants, and PTRN-1 localization is regulated by DAPK-1. DAPK-1 and PTRN-1 physically interact in co-immunoprecipitation experiments, and DAPK-1 itself undergoes MT-dependent transport. Our results uncover an unexpected interdependence of DAPK-1 and the microtubule cytoskeleton in maintenance of epidermal integrity.

  3. 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…

  4. 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…

  5. 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. ...

  6. 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…

  7. 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…

  8. 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.

  9. Feline epidermal nevi resembling human inflammatory linear verrucous epidermal nevus.

    PubMed

    Sato, Masafumi; Kariya, Kazuhiro; Matsumoto, Munetaka; Itoh, Miyuki; Kobayashi, Yoshiyasu; Nishifuji, Koji; Kamiie, Junichi; Shirota, Kinji

    2012-10-01

    Multiple, pigmented, verrucous, cutaneous lesions in a 2-year-old female cat were pathologically examined. The lesions were linearly arranged on the right side of the body, and had developed along with moderate pruritus since infancy. Histologically, prominent exophytic, papillomatous outgrowths of the epidermis and acanthosis with intense ortho and parakeratotic hyperkeratosis were characteristic of the lesions. Dermal inflammation with mononuclear cells, neutrophils, and eosinophils was also noted. Inclusion bodies, cellular degeneration, and intranuclear viral particles suggesting papillomavirus infection in the keratinocytes were not observed. Papillomavirus antigen and DNA were not detected in the lesions by immunohistochemistry and polymerase chain reaction, respectively. In accordance with these clinical and histopathological features, the cutaneous lesions of the present cat were diagnosed as epidermal nevi, which were consistent with human inflammatory linear verrucous epidermal nevi.

  10. Epidermal barrier in hereditary ichthyoses, atopic dermatitis, and psoriasis.

    PubMed

    Schmuth, Matthias; Blunder, Stefan; Dubrac, Sandrine; Gruber, Robert; Moosbrugger-Martinz, Verena

    2015-11-01

    Several skin disorders are associated with impaired skin barrier function. Primary dysfunction is caused by monogenic defects in key components of the epidermis (for example ichthyoses). Secondary barrier impairment occurs in inflammatory dermatoses marked by disturbed epidermal homeostasis (eczema, psoriasis, etc.). In these disorders, inflammation impedes the synthesis or maintenance of skin barrier components. Recent evidence suggests a combination of primary and secondary barrier dysfunction in atopic dermatitis and, to a lesser extent, also in psoriasis. In the future, subtypes of atopic dermatitis may likely be defined, in which one or the other is prevalent.

  11. 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

  12. Epidermal stem cells: interactions in developmental environments.

    PubMed

    Bickenbach, Jackie R; Grinnell, Katie L

    2004-10-01

    Homeostasis of continuously renewing adult tissues, such as the epidermis of the skin, is maintained by epidermal stem cells (EpiSC), which are a small population of undifferentiated, self-renewing basal keratinocyte cells that produce daughter transit amplifying (TA) cells to make up the majority of the proliferative basal cell population in the epidermis. We have isolated EpiSC from neonatal and adult skin, and shown that these cells can regenerate an epidermis that lasts long term in vitro and in vivo, and that permanently expresses a recombinant gene in the regenerated tissue (Bickenbach and Dunnwald, 2000; Dunnwald et al., 2001). When we injected murine EpiSC into the developing blastocyst environment of the mouse, we found that both neonatal and adult EpiSC retained some ability to participate in the formation of tissues from all three germ layers (Liang and Bickenbach, 2002; Bickenbach and Chinnathambi, 2004; Liang et al., 2004). Although it appears evident that EpiSC act as pluripotent stem cells, how this reprogramming takes place is not understood. EpiSC might directly transdifferentiate into other cell types or they might first dedifferentiate into a more primitive cell type, and then proceed to develop along a cell lineage pathway. To begin to unravel this, we co-cultured EpiSC with embryonic stem (ES) cells, and found that EpiSC could alter their cell lineage protein expression to that of a more primitive cell type. We also placed EpiSC in a wounded environment and found that EpiSC interacted with the mesenchymal cells repopulating the wound bed. Our findings indicate that the population of cells that we isolate as EpiSC has a pluripotent capability. This has led us to postulate a paradigm shift for somatic stem cells. We propose that tissues maintain a sequestered population of uncommitted stem cells that retain a regenerative response which is enhanced when the cells are exposed to developmental or stress influences.

  13. 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.

  14. 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

  15. TNF is required for the induction but not the maintenance of compression-induced BME signals in murine tail vertebrae: limitations of anti-TNF therapy for degenerative disc disease.

    PubMed

    Papuga, M Owen; Kwok, Edmund; You, Zhigang; Rubery, Paul T; Dougherty, Paul E; Pryhuber, Gloria; Beck, Christopher A; Hilton, Matthew J; Awad, Hani A; Schwarz, Edward M

    2011-09-01

    While bone marrow edema (BME) is diagnostic of spondyloarthropathy, its nature remains poorly understood. In contrast, BME in ankylosing spondylitis is caused by tumor necrosis factor (TNF)-induced vascular and cellular changes. To investigate the relationship between chronic compression and TNF signaling in compression-induced BME we utilized a tail vertebrae compression model with WT, TNF-Tg, and TNFR1&2-/- mice to evaluate: (i) healing following release of chronic compression, (ii) induction of BME in the absence of TNFR, and (iii) efficacy of anti-TNF therapy. Compression-induced normalized marrow contrast enhancement (NMCE) in WT was significantly decreased threefold (p < 0.01) within 2 weeks of release, while the NMCE values in TNF-Tg vertebrae remained elevated, but had a significant decrease (p < 0.05) by 6 weeks after the release of compression. TNFR1&2-/- mice were resistant to compression-induced BME. Anti-TNF therapy did not affect NMCE versus placebo. Histological examination revealed that NMCE values significantly correlated with marrow vascularity and cellularity (p < 0.05), which account for 76% of the variability of NMCE. Collectively, these data demonstrate a critical role for TNF in the induction of chronic compression-induced BME, but not in its maintenance. Amelioration of BME is achieved through biomechanical stability, but is not affected by anti-TNF therapy.

  16. 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

  17. Overexpression of Transcription Factor Sp2 Inhibits Epidermal Differentiation and Increases Susceptibility to Wound and Carcinogen-Induced Tumorigenesis

    PubMed Central

    Kim, Tae-Hyung; Chiera, Shannon L.; Linder, Keith E.; Trempus, Carol S.; Smart, Robert C.; Horowitz, Jonathan M.

    2010-01-01

    Sp proteins are evolutionarily-conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell-cycle progression. De-regulated expression of certain Sp proteins is associated with the formation of a variety of human tumors, however direct evidence that any given Sp protein is oncogenic has been lacking. Here we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound- and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within two weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional impact. PMID:20959487

  18. WHC Maintenance

    NASA Image and Video Library

    2009-04-28

    ISS019-E-011464 (28 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the waste and hygiene compartment located in the Destiny laboratory of the International Space Station.

  19. WHC Maintenance

    NASA Image and Video Library

    2009-04-28

    ISS019-E-011471 (28 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the waste and hygiene compartment located in the Destiny laboratory of the International Space Station.

  20. Transcriptional profiling of epidermal differentiation.

    PubMed

    Radoja, Nada; Gazel, Alix; Banno, Tomohiro; Yano, Shoichiro; Blumenberg, Miroslav

    2006-10-03

    In epidermal differentiation basal keratinocytes detach from the basement membrane, stop proliferating, and express a new set of structural proteins and enzymes, which results in an impermeable protein/lipid barrier that protects us. To define the transcriptional changes essential for this process, we purified large quantities of basal and suprabasal cells from human epidermis, using the expression of beta4 integrin as the discriminating factor. The expected expression differences in cytoskeletal, cell cycle, and adhesion genes confirmed the effective separation of the cell populations. Using DNA microarray chips, we comprehensively identify the differences in genes expressed in basal and differentiating layers of the epidermis, including the ECM components produced by the basal cells, the proteases in both the basal and suprabasal cells, and the lipid and steroid metabolism enzymes in suprabasal cells responsible for the permeability barrier. We identified the signaling pathways specific for the two populations and found two previously unknown paracrine and one juxtacrine signaling pathway operating between the basal and suprabasal cells. Furthermore, using specific expression signatures, we identified a new set of late differentiation markers and mapped their chromosomal loci, as well as a new set of melanocyte-specific markers. The data represent a quantum jump in understanding the mechanisms of epidermal differentiation.

  1. Clinical considerations for epidermal necrolysis.

    PubMed

    Ellender, Ryan P; Peters, Cacey W; Albritton, Hannah L; Garcia, Andrew J; Kaye, Alan David

    2014-01-01

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a spectrum of acute life-threatening mucocutaneous reactions that differ only in severity. Both diseases are characterized by mucous membrane and skin involvement, are often caused by medications, and are collectively known as epidermal necrolysis (EN). A severity of illness score has been devised to predict prognosis in patients with EN. The scoring system addresses 7 prognostic factors. Patients with EN require supportive care. Those with extensive skin involvement should be admitted to an intensive care unit or burn unit if possible. Suspected, as well as unnecessary, medications should be discontinued. Baseline laboratory tests, imaging, cultures, and biopsies should be obtained. Intravenous access should be established and hydration and nutritional support begun. Daily oral care, wound care, pain control, and early physician consultation are also important aspects of treatment. EN requires early diagnosis, appropriate workup, and appropriate treatment to minimize potential morbidity and mortality. In many clinicians' experience, EN is rare; therefore, education and improved understanding of the potential causes and appropriate treatment regimens are vital when confronted with such a patient.

  2. 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

  3. 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.

  4. Conventional murine gene targeting.

    PubMed

    Zimmermann, Albert G; Sun, Yue

    2013-01-01

    Murine gene knockout models engineered over the last two decades have continued to demonstrate their potential as invaluable tools in understanding the role of gene function in the context of normal human development and disease. The more recent elucidation of the human and mouse genomes through sequencing has opened up the capability to elucidate the function of every human gene. State-of-the-art mouse model generation allows, through a multitude of experimental steps requiring careful standardization, gene function to be reliably and predictably ablated in a live model system. The application of these standardized methodologies to directly target gene function through murine gene knockout has to date provided comprehensive and verifiable genetic models that have contributed tremendously to our understanding of the cellular and molecular pathways underlying normal and disease states in humans. The ensuing chapter provides an overview of the latest steps and procedures required to ablate gene function in a murine model.

  5. 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.

  6. Toxic epidermal necrolysis: an update

    PubMed Central

    Tiwari, Prashant; Panik, Rajnikant; Bhattacharya, Arin; Ahirwar, Dheeraj; Chandy, Anish

    2013-01-01

    Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a rare, life-threatening dermatological condition that is usually induced by reaction to medications. It is characterized by the detachment of the top layer of skin (the epidermis) from the lower layers of the skin (the dermis) all over the body. There is broad agreement in medical literature that TEN can be considered a more severe form of Stevens Johnson syndrome, and debate whether it falls on a spectrum of disease that includes erythema multiforme. Some authors consider that there is an overlap between the two syndromes (usually between 10% and 30% of skin detachment). This article deals with history, epidemiology, diagnosis, pathophysiology treatment and management of TEN.

  7. Methadone maintenance.

    PubMed

    Russell-Taylor, W J

    1975-07-01

    Management of heroin addiction with oral methadone continues to create controversy. Since the first Dole-Nyswander experiments were reported almost a decade ago, methadone maintenance programs have been started in every major city in North America at an estimated public cost in the hundreds of millions of tax dollars. By the end of 1972, the United States alone spending at an annual rate in excess of $250 million, and an expenditure rate in excess of one billion dollars was occurring by the end of 1973. Despite the FDA investigational New Drug status of methadone when used for this purpose, objective data have still not been generated to substantiate the worth of Narcotic Substitution Therapy. Iatrogenic consequences are on the increase, and scepticism is growing among most pharmacologists. A critical evaluation of the entire methadone maintenance approach is being advocated by many and being attempted by some. Data currently being generated at the Philadelphia General Hospital suggest that many patients may have been better managed without methadone.

  8. Epidermal electronic systems for sensing and therapy

    NASA Astrophysics Data System (ADS)

    Lu, Nanshu; Ameri, Shideh K.; Ha, Taewoo; Nicolini, Luke; Stier, Andrew; Wang, Pulin

    2017-04-01

    Epidermal electronic system is a class of hair thin, skin soft, stretchable sensors and electronics capable of continuous and long-term physiological sensing and clinical therapy when applied on human skin. The high cost of manpower, materials, and photolithographic facilities associated with its manufacture limit the availability of disposable epidermal electronics. We have invented a cost and time effective, completely dry, benchtop "cut-and-paste" method for the green, freeform and portable manufacture of epidermal electronics within minutes. We have applied the "cut-and-paste" method to manufacture epidermal electrodes, hydration and temperature sensors, conformable power-efficient heaters, as well as cuffless continuous blood pressure monitors out of metal thin films, two-dimensional (2D) materials, and piezoelectric polymer sheets. For demonstration purpose, we will discuss three examples of "cut-and-pasted" epidermal electronic systems in this paper. The first will be submicron thick, transparent epidermal graphene electrodes that can be directly transferred to human skin like a temporary transfer tattoo and can measure electrocardiogram (ECG) with signal-to-noise ratio and motion artifacts on par with conventional gel electrodes. The second will be a chest patch which houses both electrodes and pressure sensors for the synchronous measurements of ECG and seismocardiogram (SCG) such that beat-to-beat blood pressure can be inferred from the time interval between the R peak of the ECG and the AC peak of the SCG. The last example will be a highly conformable, low power consumption epidermal heater for thermal therapy.

  9. Psoriatic architecture constructed by epidermal remodeling.

    PubMed

    Iizuka, Hajime; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2004-08-01

    Epidermal remodeling is the concept that epidermal architecture is determined by a simple self-organizing mechanism; epidermal hyperproliferation constructs typical psoriatic architecture. This is based on the assumption that the enlargements in both the two-dimensional proliferative compartment (basal cell layer) and three-dimensional whole epidermal volume coexist. During this process, the dermal papillae become markedly, but passively, expanded by enlargement of the proliferative compartment. This creates a considerable shrinkage force against the crowded basal cell layer, which is forced to lose adherence to the dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis characterized by cell detachment, and, consequently, a markedly diminished epidermal turnover time in psoriasis. The papillary shrinkage force also explains the fact that dermal papillary height does not exceed a certain limit. At the cessation of hyperproliferation a normalisation remodeling takes place toward normal tissue architecture. Thus the concept of epidermal remodeling explains the self-organizing mechanism of the architectural change in psoriasis, which is essentially a reversible disorder depending on epidermal hyperproliferation.

  10. Beyond expectations: novel insights into epidermal keratin function and regulation.

    PubMed

    Homberg, Melanie; Magin, Thomas M

    2014-01-01

    The epidermis is a stratified epithelium that relies on its cytoskeleton and cell junctions to protect the body against mechanical injury, dehydration, and infections. Keratin intermediate filament proteins are involved in many of these functions by forming cell-specific cytoskeletal scaffolds crucial for the maintenance of cell and tissue integrity. In response to various stresses, the expression and organization of keratins are altered at transcriptional and posttranslational levels to restore tissue homeostasis. Failure to restore tissue homeostasis in the presence of keratin gene mutations results in acute and chronic skin disorders for which currently no rational therapies are available. Here, we review the recent progress on the role of keratins in cytoarchitecture, adhesion, signaling, and inflammation. By focusing on epidermal keratins, we illustrate the contribution of keratin isotypes to differentiated epithelial functions.

  11. Epidermal growth factor receptor-targeted therapy for pancreatic cancer.

    PubMed

    Xiong, Henry Q; Abbruzzese, James L

    2002-10-01

    Epidermal growth factor receptor (EGFR) plays an important role in tumor development and maintenance. It is a cell surface molecule that mediates signal transduction from the cell surface to cytoplasm. Elevated expression of EGFR or its ligand correlates with worse prognosis in a variety of human cancers. Therefore, blockade of EGFR activity would provide a novel strategy for the treatment of cancer. Two classes of EGFR inhibitors, monoclonal antibodies and tyrosine kinase inhibitors, have been described. The preclinical activity of these EGFR inhibitors and phase I clinical data are summarized in this article. A phase II trial of the EGFR inhibitor IMC-C225 in combination with gemcitabine for patients with advanced pancreatic cancer is discussed. Copyright 2002, Elsevier Science (USA). All rights reserved.

  12. The epidermal growth factor receptor family: Biology driving targeted therapeutics

    PubMed Central

    Wieduwilt, M. J.; Moasser, M. M.

    2011-01-01

    The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy. PMID:18259690

  13. Review of Toxic Epidermal Necrolysis

    PubMed Central

    Harris, Victoria; Jackson, Christopher; Cooper, Alan

    2016-01-01

    Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation. There is uncertainty around the accepted management of TEN. The lack of definitive management guidelines for TEN is explained in part by the rarity of the disease and its high mortality rate, which makes it difficult to conduct randomised control trials on emerging therapies. Developments have been made in pharmacogenomics, with numerous HLA alleles identified; however, these have largely been ethnically specific. These associations have translated into screening recommendations for Han Chinese. PMID:27999358

  14. Rapidly Developing Toxic Epidermal Necrolysis

    PubMed Central

    Nielsen, Jonas

    2013-01-01

    Severe cutaneous reactions with potentially fatal outcomes can have many different causes. The Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated. Urgent active therapy is required. Prompt recognition and withdrawal of suspect drug and rapid intervention can result in favourable outcome. No further international guidelines for treatment exist, and much of the treatment relies on old or experimental concepts with no scientific evidence. We report on a 54-year-old man experiencing rapidly developing drug-induced severe TEN and presented multiorgan failure involving the respiratory and circulatory system, coagulopathy, and renal insufficiency. Detachment counted 30% of total body surface area (TBSA). SCORTEN = 5, indicating a mortality rate >90%. The patient was sedated and mechanically ventilated, supported with fluids and inotropes to maintain a stable circulation. Component therapy was guided by thromboelastography (TEG). The patient received plasmapheresis, and shock reversal treatment was initiated. He was transferred to a specialized intensive care burn unit within 24 hours from admittance. The initial care was continued, and hemodialysis was started. Pulmonary, circulatory, and renal sequelae resolved with intensive care, and re-epithelialization progressed slowly. The patient was discharged home on hospital day 19. PMID:24069541

  15. Effect of ingested concentrate and components of sake on epidermal permeability barrier disruption by UVB irradiation.

    PubMed

    Hirotsune, Masato; Haratake, Akinori; Komiya, Aya; Sugita, Jun; Tachihara, Toru; Komai, Tsuyoshi; Hizume, Kazuhisa; Ozeki, Kenji; Ikemoto, Takeshi

    2005-02-23

    Daily topical applications of the concentrate of sake (CS) have been shown to reduce epidermal barrier disruption in murine skin caused by ultraviolet B (UVB) radiation, while one of the components of sake, ethyl alpha-D-glucoside (alpha-EG), also reduces barrier disruption. We confirmed the effect of oral ingestion of various doses of CS on epidermal barrier disruption caused by UVB irradiation in hairless mice. Then, to identify the effective components, we quantitatively analyzed alpha-EG, organic acids, and glycerol, the main components of CS, and examined the effect of various concentration of each on barrier disruption. alpha-EG and organic acids showed comparable results to CS itself, and transepidermal water loss levels in murine skin were significantly decreased as compared with the control. Furthermore, an investigation of the dose dependency of these agents was performed and the results showed the significant effectiveness of alpha-EG. In addition, red wine concentrate (WC) and beer concentrate (BC) were examined in order to confirm the unique effects of CS. Similar effects were not found with WC and BC.

  16. Mechanotransduction in epidermal Merkel cells.

    PubMed

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

    2015-01-01

    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.

  17. 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

  18. 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.

  19. Id2 Is Dispensable for Myc-Induced Epidermal Neoplasia

    PubMed Central

    Murphy, Daniel J.; Swigart, Lamorna Brown; Israel, Mark A.; Evan, Gerard I.

    2004-01-01

    We have previously described a transgenic mouse model of epidermal neoplasia wherein expression of a switchable form of c-Myc, MycERTAM, is targeted to the postmitotic suprabasal keratinocytes of murine epidermis via the involucrin promoter. Sustained activation of c-MycERTAM results in a progressive neoplastic phenotype characterized by aberrant ectopic proliferation and delayed differentiation of suprabasal keratinocytes, culminating in papillomatosis. Transcription of the Id2 gene is regulated by Myc family proteins. Moreover, Id2 is implicated as a pivotal determinant of cell fate in multiple lineages and has a demonstrated role in mediating Myc-dependent cell proliferation in vitro through its interaction with retinoblastoma protein. Using Id2 nullizygous mice, we assessed in vivo the requirement for Id2 in mediating Myc-induced papilloma formation in skin. We show that absence of Id2 has no discernible impact on any measurable attribute of Myc function or on the timing or extent of eventual tumor formation. Thus, our data argue against any essential role for Id2 in mediating Myc action in vivo. PMID:14966287

  20. 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

  1. 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…

  2. Maintenance Management Update.

    ERIC Educational Resources Information Center

    Sternloff, Robert E.

    1987-01-01

    Current trends in park maintenance are overviewed, including maintenance impact statements, avoidance of cost through efficient use and national resource conservation, horticultural accomplishments that influence maintenance management, and vandalism prevention. (CB)

  3. Maintenance Management Update.

    ERIC Educational Resources Information Center

    Sternloff, Robert E.

    1987-01-01

    Current trends in park maintenance are overviewed, including maintenance impact statements, avoidance of cost through efficient use and national resource conservation, horticultural accomplishments that influence maintenance management, and vandalism prevention. (CB)

  4. 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

  5. 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

  6. Epidermal homeostasis: the role of the growth hormone and insulin-like growth factor systems.

    PubMed

    Edmondson, Stephanie R; Thumiger, Susan P; Werther, George A; Wraight, Christopher J

    2003-12-01

    GH and IGF-I and -II were first identified by their endocrine activity. Specifically, IGF-I was found to mediate the linear growth-promoting actions of GH. It is now evident that these two growth factor systems also exert widespread activity throughout the body and that their actions are not always interconnected. The literature highlights the importance of the GH and IGF systems in normal skin homeostasis, including dermal/epidermal cross-talk. GH activity, sometimes mediated via IGF-I, is primarily evident in the dermis, particularly affecting collagen synthesis. In contrast, IGF action is an important feature of the dermal and epidermal compartments, predominantly enhancing cell proliferation, survival, and migration. The locally expressed IGF binding proteins play significant and complex roles, primarily via modulation of IGF actions. Disturbances in GH and IGF signaling pathways are implicated in the pathophysiology of several skin perturbations, particularly those exhibiting epidermal hyperplasia (e.g., psoriasis, carcinomas). Additionally, many studies emphasize the potential use of both growth factors in the treatment of skin wounds; for example, burn patients. This overview concerns the role and mechanisms of action of the GH and IGF systems in skin and maintenance of epidermal integrity in both health and disease.

  7. Epidermal barrier dysfunction in atopic dermatitis.

    PubMed

    Cork, Michael J; Danby, Simon G; Vasilopoulos, Yiannis; Hadgraft, Jonathan; Lane, Majella E; Moustafa, Manar; Guy, Richard H; Macgowan, Alice L; Tazi-Ahnini, Rachid; Ward, Simon J

    2009-08-01

    Atopic dermatitis (AD) is a multifactorial, heterogenous disease that arises as a result of the interaction between both environmental and genetic factors. Changes in at least three groups of genes encoding structural proteins, epidermal proteases, and protease inhibitors predispose to a defective epidermal barrier and increase the risk of developing AD. Loss-of-function mutations found within the FLG gene encoding the structural protein, filaggrin, represent the most significant genetic factor predisposing to AD identified to date. Enhanced protease activity and decreased synthesis of the lipid lamellae lead to exacerbated breakdown of the epidermal barrier. Environmental factors, including the use of soap and detergents, exacerbate epidermal barrier breakdown, attributed to the elevation of stratum corneum pH. A sustained increase in pH enhances the activity of degradatory proteases and decreases the activity of the lipid synthesis enzymes. The strong association between both genetic barrier defects and environmental insults to the barrier with AD suggests that epidermal barrier dysfunction is a primary event in the development of this disease. Our understanding of gene-environment interactions should lead to a better use of some topical products, avoidance of others, and the increased use and development of products that can repair the skin barrier.

  8. Toxic epidermal necrolysis (Lyell's disease).

    PubMed

    Lissia, Mario; Mulas, Pietro; Bulla, Antonio; Rubino, Corrado

    2010-03-01

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions, characterized by a low incidence but high mortality, initially described as separate entities, but today considered variants of the same pathologic process and differing only for severity. The majority of cases appear to be related to idiosyncratic drug reactions. The drugs most commonly involved are: antibiotics such as sulfonamides, beta-lactam, tetracyclines and quinolones; anticonvulsants such as phenytoin, phenobarbital and carbamazapine; antiretroviral drugs; nonsteroidal anti-inflammatory drugs, allopurinol. There is common agreement to consider TEN as the manifestation of a disregulated immune reaction against epithelial cells. During the first stages of TEN, apoptosis mediates keratinocyte death and the pivotal role of Fas-FasL pathway activation during TEN is undoubted. T cell cytotoxicity, demonstrated during TEN, has been shown to be mediated by the perforin-granzyme pathway. It seems, also, clear that a peculiar cytokine pattern plays an important role in TEN pathogenesis. The cutaneous findings result in an acute macular erythematous rash with bullae. These lesions rapidly exhibit Nikolsky's sign and a separation of large sheets of epidermis from the dermis and a subsequent localised shedding develops rapidly, which can become very extensive. When feasible, admission in burn or intensive care unit, positioning the patients in air-fluidised beds, is universally considered crucial in TEN treatment. The prompt withdrawal of the suspected drug, fluid and electrolyte replacement and topical wound care are the first line of therapy. The use of corticosteroids has been abandoned and the role of immunosuppressants, despite some success, is not well defined and is not considered as a standard. A trial comparing thalidomide versus placebo in TEN patients was suspended because mortality rate increased in the treated group. Infliximab, a chimeric monoclonal

  9. Squamous cell carcinoma arising in a multiple verrucous epidermal nevus*

    PubMed Central

    Yarak, Samira; Machado, Taila Yuri Siqueira; Ogawa, Marilia Marufuji; Almeida, Mirian Luzia da Silva; Enokihara, Milvia Maria Simões e Silva; Porro, Adriana Maria

    2016-01-01

    Verrucous epidermal nevi are hamartomatous lesions of the epidermis that, unlike other epidermal nevi (such as sebaceous nevus or nevus comedonicus), are rarely associated with malignant neoplasms. The majority of squamous cell carcinoma develop in linear or multiple epidermal nevus and rarely in solitary epidermal nevus. In general, the prognosis is favorable. We report a case of well-differentiated invasive squamous cell carcinoma arising from a multiple verrucous epidermal nevus. Although there is no consensus on prophylactic removal of epidermal nevus, its removal and biopsy should be considered if changes occur. PMID:28300931

  10. Carbamzepine-induced toxic epidermal necrolysis

    PubMed Central

    Chowta, Nithyananda K.; Chowta, Mukta N.; Ramapuram, John; Kumar, Pramod; Fazil, Abul

    2011-01-01

    Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a widespread life-threatening mucocutaneous disease where there is extensive detachment of the skin and mucous membrane. Many factors involved in the etiology of TEN including adverse drug reactions. Here we are reporting a case of toxic epidermal necrolysis in an adult male patient after receiving carbamazepine in a 38 year old male. On the 18th day of carbamazepine, patient developed blisters which first appeared on the trunk, chest and arms. The erythematous rash was covering almost all over the body with epidermal detachment of 70% body surface area. There was loss of eye lashes, congestion of conjunctiva with mucopurulent discharge and exposure keratitis. The clinical impression was TEN induced by carbamazepine. Carbamazepine was stopped immediately. He was treated with high dose intravenous betamethasone and systemic and topical antibiotics. After one month, the progression of the skin lesions halted and he was discharged. PMID:21814379

  11. [Beyond immunopathogenesis. Insulin resistance and "epidermal dysfunction"].

    PubMed

    Boehncke, W-H; Boehncke, S; Buerger, C

    2012-03-01

    Insulin is a central player in the regulation of metabolic as well as non-metabolic cells: inefficient signal transduction (insulin resistance) not only represents the cornerstone in the pathogenesis of type 2 diabetes mellitus, but also drives atherosclerosis through inducing endothelial dysfunction. Last but not least epidermal homeostasis depends on insulin. We summarize the effects of insulin on proliferation and differentiation of human keratinocytes as well as the relevance of cytokine-induced insulin resistance for alterations in epidermal homeostasis characteristic for psoriasis. Kinases involved in both insulin- as well as cytokine-receptor signaling represent potential targets for innovative therapeutics. Such small molecules would primarily normalize "epidermal dysfunction", thus complementing the immunomodulatory strategies of today's biologics.

  12. Epidermal stem cells and their epigenetic regulation.

    PubMed

    Shen, Qi; Jin, Hongchuan; Wang, Xian

    2013-08-30

    Stem cells play an essential role in embryonic development, cell differentiation and tissue regeneration. Tissue homeostasis in adults is maintained by adult stem cells resident in the niches of different tissues. As one kind of adult stem cell, epidermal stem cells have the potential to generate diversified types of progeny cells in the skin. Although its biology is still largely unclarified, epidermal stem cells are widely used in stem cell research and regenerative medicine given its easy accessibility and pluripotency. Despite the same genome, cells within an organism have different fates due to the epigenetic regulation of gene expression. In this review, we will briefly discuss the current understanding of epigenetic modulation in epidermal stem cells.

  13. Effect of glucocorticosteroids on epidermal Langerhans cells

    PubMed Central

    1982-01-01

    The effects of topical and systemic administration of various glucocorticoids on the density of epidermal Langerhans cells (LC) were studied in guinea pigs. Glucocorticoids, such as betamethasone dipropionate and valerate, caused a marked decrease in LC demonstrable by staining for cell membrane ATPase activity and Ia antigens. By electronmicroscopy, LC also showed morphologic alterations. The observed decrements in LC density correlated with the concentration and known vasoconstrictive potency of the glucocorticoids administered. The anti-inflammatory action of glucocorticoids in skin disorders may, at least in part, be through their ability to alter epidermal LC, thus interfering with the antigen-presenting functions of these cells. PMID:6459400

  14. [Mucocutaneous diseases and murine models with death of keratinocytes induced by lichenoid tissue reaction/interface dermatitis].

    PubMed

    Okiyama, Naoko

    2015-01-01

    A set of histopathological elements with death of epidermal basal cell layer keratinocytes along with inflammatory cell infiltration distinguishes lichenoid tissue reaction (LTR)/interface dermatitis (IFD) from other inflammatory mucocutaneous diseases. The LTR/IFD can be seen in skin disorders like as lichen planus, acute graft-versus-host disease, lupus erythematosus, dermatomyositis, and toxic epidermal necrolysis/Stevesn-Johnson syndrome. Clinical and basic researches suggested that cytotoxic CD8 T cells producing interferon-γ and FasL are final effector cells to cause apoptosis of keratinocyte. Some murine models of LTR/IFD have been established, for example, LTR/IFD reactions of keratinocyte-specific ovalbumin (OVA)-transgenic mice after OVA-specific T-cell-receptor(+)CD8 T cells. By analysis of the murine model, a new class of immunosuppressant, a JAK inhibitor, has been suggested as a new candidate for treatment of LTR/IFD.

  15. A homolog of Drosophila grainy head is essential for epidermal integrity in mice.

    PubMed

    Ting, Stephen B; Caddy, Jacinta; Hislop, Nikki; Wilanowski, Tomasz; Auden, Alana; Zhao, Lin-Lin; Ellis, Sarah; Kaur, Pritinder; Uchida, Yoshikazu; Holleran, Walter M; Elias, Peter M; Cunningham, John M; Jane, Stephen M

    2005-04-15

    The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.

  16. 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

  17. Grounds Maintenance Cost Report.

    ERIC Educational Resources Information Center

    Joice, Donald K.

    A grounds maintenance study was accomplished over the period of March 1965 through February 1966 to--(1) determine current grounds maintenance cost distribution; (2) provide basis for future grounds maintenance budgeting, and (3) provide basic data by which future landscape project designs can be developed to project or reduce maintenance costs.…

  18. 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.

  19. SEROLOGICALLY DEMONSTRABLE ALLOANTIGENS OF MOUSE EPIDERMAL CELLS

    PubMed Central

    Scheid, Margrit; Boyse, Edward A.; Carswell, Elizabeth A.; Old, Lloyd J.

    1972-01-01

    Single cells were prepared from mouse tail epidermis by a method which gives high viability counts and so permits their use in cytotoxicity tests. According to tests with standard alloantisera, the antigen phenotype of mouse epidermal cells is H-2+θ+Sk+H-Y+TL-Ly-A-Ly-B,C-PC-. The skin differentiation alloantigen Sk, which is responsible for homograft reactions directed selectively against skin, is expressed also on brain, but not on other cell types; it is present on the transplanted neuroblastoma C1300. Cytotoxicity tests with epidermal cells of H-2 congenic mouse stocks confirm that the Sk locus is not closely linked to H-2. The lymphoid cell differentiation antigen θ also is present on both epidermal cells and brain. Mice frequently retain θ-incompatible or Sk-incompatible skin grafts although they have formed substantial titers of θ or Sk antibody in response to grafting. Male (H-Y) antigen is demonstrable on epidermal cells by cytotoxicity tests with H-Y antibody, as it is also on one other type of cell, spermatozoa. PMID:4553016

  20. Opsin Expression in Human Epidermal Skin

    PubMed Central

    Haltaufderhyde, Kirk; Ozdeslik, Rana N; Wicks, Nadine L; Najera, Julia A; Oancea, Elena

    2015-01-01

    Human skin is constantly exposed to solar light containing visible and ultraviolet radiation (UVR), a powerful skin carcinogen. UVR elicits cellular responses in epidermal cells via several mechanisms: direct absorption of short-wavelength UVR photons by DNA, oxidative damage caused by long-wavelength UVR, and, as we recently demonstrated, via a retinal-dependent G protein-coupled signaling pathway. Because the human epidermis is exposed to a wide range of light wavelengths, we investigated whether opsins, light-activated receptors that mediate photoreception in the eye, are expressed in epidermal skin to potentially serve as photosensors. Here we show that four opsins—OPN1-SW, OPN2, OPN3 and OPN5—are expressed in the two major human epidermal cell types, melanocytes and keratinocytes, and the mRNA expression profile of these opsins does not change in response to physiological UVR doses. We detected two OPN3 splice variants present in similar amounts in both cell types and three OPN5 splice isoforms, two of which encode truncated proteins. Notably, OPN2 and OPN3 mRNA were significantly more abundant than other opsins and encoded full-length proteins. Our results demonstrate that opsins are expressed in epidermal skin cells and suggest that they might initiate light–induced signaling pathways, possibly contributing to UVR phototransduction. PMID:25267311

  1. Opsin expression in human epidermal skin.

    PubMed

    Haltaufderhyde, Kirk; Ozdeslik, Rana N; Wicks, Nadine L; Najera, Julia A; Oancea, Elena

    2015-01-01

    Human skin is constantly exposed to solar light containing visible and ultraviolet radiation (UVR), a powerful skin carcinogen. UVR elicits cellular responses in epidermal cells via several mechanisms: direct absorption of short-wavelength UVR photons by DNA, oxidative damage caused by long-wavelength UVR, and, as we recently demonstrated, via a retinal-dependent G protein-coupled signaling pathway. Because the human epidermis is exposed to a wide range of light wavelengths, we investigated whether opsins, light-activated receptors that mediate photoreception in the eye, are expressed in epidermal skin to potentially serve as photosensors. Here we show that four opsins—OPN1-SW, OPN2, OPN3 and OPN5—are expressed in the two major human epidermal cell types, melanocytes and keratinocytes, and the mRNA expression profile of these opsins does not change in response to physiological UVR doses. We detected two OPN3 splice variants present in similar amounts in both cell types and three OPN5 splice isoforms, two of which encode truncated proteins. Notably, OPN2 and OPN3 mRNA were significantly more abundant than other opsins and encoded full-length proteins. Our results demonstrate that opsins are expressed in epidermal skin cells and suggest that they might initiate light-induced signaling pathways, possibly contributing to UVR phototransduction. © 2014 The Authors. Photochemistry and Photobiology published by Wiley Periodicals, Inc. on behalf of American Society for Photobiology.

  2. Toxic epidermal necrolysis from a cigarette burn.

    PubMed

    Parker, Joshua R; Berkeley, Ross P

    2010-05-01

    Toxic epidermal necrolysis is a rare disease that is most often drug-induced but can be of idiopathic origin. We present a case that originated at the site of a cigarette burn to the forearm and review the key elements of physical exam findings and management of this life-threatening dermatological condition, which needs to be promptly recognized to decrease patient mortality.

  3. A Role for Endogenous Transforming Growth Factor β1 in Langerhans Cell Biology:  The Skin of   Transforming Growth Factor β1 Null Mice Is Devoid of  Epidermal Langerhans Cells

    PubMed Central

    Borkowski, Teresa A.; Letterio, John J.; Farr, Andrew G.; Udey, Mark C.

    1996-01-01

    Transforming growth factor β1 (TGF-β1) regulates leukocytes and epithelial cells. To determine whether the pleiotropic effects of TGF-β1, a cytokine that is produced by both keratinocytes and Langerhans cells (LC), extend to epidermal leukocytes, we characterized LC (the epidermal contingent of the dendritic cell [DC] lineage) and dendritic epidermal T cells (DETC) in TGF-β1 null (TGF-β1 −/−) mice. I-A+ LC were not detected in epidermal cell suspensions or epidermal sheets prepared from TGF-β1 −/− mice, and epidermal cell suspensions were devoid of allostimulatory activity. In contrast, TCR-γδ+ DETC were normal in number and appearance in TGF-β1 −/− mice and, importantly, DETC represented the only leukocytes in the epidermis. Immunolocalization studies revealed CD11c+ DC in lymph nodes from TGF-β1 −/− mice, although gp40+ DC were absent. Treatment of TGF-β1 −/− mice with rapamycin abrogated the characteristic inflammatory wasting syndrome and prolonged survival indefinitely, but did not result in population of the epidermis with LC. Thus, the LC abnormality in TGF-β1 −/− mice is not a consequence of inflammation in skin or other organs, and LC development is not simply delayed in these animals. We conclude that endogenous TGF-β1 is essential for normal murine LC development or epidermal localization. PMID:8976197

  4. Establishing maintenance performance indicators

    SciTech Connect

    Baca, B.

    1994-10-01

    Maintenance Performance Indicators (PI) specify where the maintenance department is and which direction it is going allowing for a quick and accurate assessment of the performance of the Maintenance Management Program (MMP). Establishing PI`s for the maintenance department will allow a measure of productivity and a means of feedback for methods improvement. Effective performance of the maintenance department directly effects plant profitability. Improvements in the quality and productivity of the maintenance work force will significantly reduce maintenance costs. The level of performance attained by the maintenance work force is usually guessed at. Guessing will not identify areas needing improvement or help to initiate a corrective action. Maintenance PI`s are required for maintenance departments whose goal is to control maintenance costs while increasing productivity. The application of basic statistical methods will allow a maintenance department to know where they are and which direction they are going. The data presented in this paper is a representation of indicators used in industry as well as developed indicators to establish a complete maintenance performance indicator program. The methodology used in developing this program can be used as a way to manage a cost effective maintenance management program.

  5. Transcriptional targets of Foxd3 in murine ES cells.

    PubMed

    Plank, Jennifer L; Suflita, Michael T; Galindo, Cristi L; Labosky, Patricia A

    2014-01-01

    Understanding gene regulatory networks controlling properties of pluripotent stem cells will facilitate development of stem cell-based therapies. The transcription factor Foxd3 is critical for maintenance of self-renewal, survival, and pluripotency in murine embryonic stem cells (ESCs). Using a conditional deletion of Foxd3 followed by gene expression analyses, we demonstrate that genes required for several developmental processes including embryonic organ development, epithelium development, and epithelial differentiation were misregulated in the absence of Foxd3. Additionally, we identified 6 novel targets of Foxd3 (Sox4, Safb, Sox15, Fosb, Pmaip1 and Smarcd3). Finally, we present data suggesting that Foxd3 functions upstream of genes required for skeletal muscle development. Together, this work provides further evidence that Foxd3 is a critical regulator of murine development through the regulation of lineage specific differentiation.

  6. Role of G-protein-coupled estrogen receptor (GPER/GPR30) in maintenance of meiotic arrest in fish oocytes.

    PubMed

    Thomas, Peter

    2017-03-01

    An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E2) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (Gs) on oocyte plasma membranes resulting in stimulation of cAMP production and maintenance of elevated cAMP levels. Studies with denuded zebrafish oocytes and with microinjection of GPER antisense oligonucleotides into oocytes have demonstrated the requirement for both ovarian follicle production of estrogens and expression of GPER on the oocyte surface for maintenance of meiotic arrest. This inhibitory action of E2 on the resumption of meiosis is mimicked by the GPER-selective agonist G-1, by the GPER agonists and nuclear ER antagonists, ICI 182,780 and tamoxifen, and also by the xenoestrogen bisphenol-A (BPA) and related alkylphenols. GPER also maintains meiotic arrest of zebrafish oocytes through estrogen- and BPA-dependent GPER activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) signaling. Interestingly, progesterone receptor component 1 (PGRMC1) is also involved in estrogen maintenance of meiotic arrest through regulation of EGFR expression on the oocyte plasma membrane. The preovulatory surge in LH secretion induces the ovarian synthesis of progestin hormones that activate a membrane progestin receptor alpha (mPRα)/inhibitory G protein (Gi) pathway. It also increases ovarian synthesis of the catecholestrogen, 2-hydroxy-estradiol-17β (2-OHE2) which inhibits the GPER/Gs/adenylyl cyclase pathway. Both of these LH actions

  7. 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

  8. 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

  9. 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

  10. Tumorigenic transformation of murine keratinocytes by the E5 genes of bovine papillomavirus type 1 and human papillomavirus type 16.

    PubMed Central

    Leptak, C; Ramon y Cajal, S; Kulke, R; Horwitz, B H; Riese, D J; Dotto, G P; DiMaio, D

    1991-01-01

    To examine the biological properties of the bovine papillomavirus type 1 (BPV) and human papillomavirus type 16 (HPV16) E5 genes, each was cloned separately into a retroviral expression vector and helper-free recombinant viruses were generated in packaging cell lines. The BPV E5 retroviruses efficiently caused morphologic and tumorigenic transformation of cultured lines of murine fibroblasts, whereas the HPV16 E5 viruses were inactive in these assays. In contrast, infection of the p117 established line of murine epidermal keratinocytes with either the BPV or the HPV16 E5 retrovirus resulted in the generation of tumorigenic cells. Pam212 murine keratinocytes were also transformed to tumorigenicity by the HPV16 E5 gene but not by the gene carrying a frameshift mutation. These results establish that the HPV16 E5 gene is a transforming gene in cells related to its normal host epithelial cells. Images PMID:1658398

  11. Abnormal epidermal changes after argon laser treatment

    SciTech Connect

    Neumann, R.A.; Knobler, R.M.; Aberer, E.; Klein, W.; Kocsis, F.; Ott, E. )

    1991-02-01

    A 26-year-old woman with a congenital port-wine stain on the forehead was treated three times at 2-month intervals with an argon laser. Six months after the last treatment, moderate blanching and mild scaling confined to the treated area was observed. A biopsy specimen of the treated area revealed a significant decrease in ectatic vessels. However, epidermal changes similar to those of actinic keratosis with disorganized cell layers and marked cytologic abnormalities were seen. Analysis of peripheral blood lymphocytes for a defect in DNA repair was negative. Multiple, argon laser-induced photothermal effects may be responsible for the changes observed in our case and may lead to premalignant epidermal transformation.

  12. Leukemoid reaction in epidermal squamous cell carcinoma.

    PubMed

    Kiyosawa, T; Hirano, S; Nakamura, J; Murata, S; Demitsu, T; Kato, H; Yaoita, H

    1996-08-01

    There have been no previous concrete reports of leukemoid reactions associated with squamous cell carcinoma originating in cutaneous tissue. Here we report a case of epidermal squamous cell carcinoma of the sacral region and an associated leukemoid reaction. The tumor invaded deeply and destroyed both the sacrum and coccyx. The white blood cell count was greater than 20,000/mm3. After resection of the tumor, white blood cells transiently decreased, but did not fall under 10,000/mm3. Post-operative infection by methicillin-resistant Staphylococcus aureus and Bacteroides caccae caused sepsis and further elevation of the leukocytes to greater than 50,000/mm3. The leukemoid reaction in the case appeared to have been caused initially by direct invasion of bone by epidermal squamous cell carcinoma and later by severe infection.

  13. Epidermal stem cell diversity and quiescence

    PubMed Central

    Watt, Fiona M; Jensen, Kim B

    2009-01-01

    Mammalian epidermis is maintained by self-renewal of stem cells and terminal differentiation of their progeny. New data reveal a diversity amongst stem cells that was previously unrecognized. Different stem cell populations have different locations and differ in whether they are quiescent or actively cycling. During normal epidermal homeostasis, each stem cell population feeds a restricted number of differentiated lineages. However, in response to injury or genetic manipulation the different pools of stem cells demonstrate multi-lineage differentiation ability. While it is well established that Wnt signalling promotes hair follicle (HF) differentiation, new observations suggest a role for EGF receptor signalling in promoting differentiation of interfollicular epidermis. NFATc1 maintains quiescence in the HF, while Lrig1 exerts the same function in the junctional zone. The stage is now set for exploring the relationship between the different epidermal stem cell populations and between quiescence and lineage selection. PMID:20049729

  14. Epidermal stem cell diversity and quiescence.

    PubMed

    Watt, Fiona M; Jensen, Kim B

    2009-08-01

    Mammalian epidermis is maintained by self-renewal of stem cells and terminal differentiation of their progeny. New data reveal a diversity amongst stem cells that was previously unrecognized. Different stem cell populations have different locations and differ in whether they are quiescent or actively cycling. During normal epidermal homeostasis, each stem cell population feeds a restricted number of differentiated lineages. However, in response to injury or genetic manipulation the different pools of stem cells demonstrate multi-lineage differentiation ability. While it is well established that Wnt signalling promotes hair follicle (HF) differentiation, new observations suggest a role for EGF receptor signalling in promoting differentiation of interfollicular epidermis. NFATc1 maintains quiescence in the HF, while Lrig1 exerts the same function in the junctional zone. The stage is now set for exploring the relationship between the different epidermal stem cell populations and between quiescence and lineage selection.

  15. 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

  16. Maintenance Management System

    DTIC Science & Technology

    1990-06-01

    maintenance opera- tions. d. Available national maintenance management system (MMS) software be utilized to develop the planning, organizing...portland cement concrete pavements to level and realign faulted areas between slabs or craks within the slab by grinding the high side. MAINTENANCE ITEM

  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,…

  19. Microform Reader Maintenance.

    ERIC Educational Resources Information Center

    Hall, Hal W.; Michaels, George H.

    1985-01-01

    Describes experiences in organizing a program of microform reader and reader/printer maintenance at Texas A & M's Sterling C. Evans Library and offers guidelines for regular machine maintenance and repair. Guidelines discussed relate to maintenance philosophy, general machine cleaning, troubleshooting, service contracts, supplies,…

  20. 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)…

  1. Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor

    PubMed Central

    1990-01-01

    The epidermis of clinically normal-appearing human skin harbors a phenotypically heterogeneous population of T lymphocytes (TCs), the majority of which are CD2+/CD3+/CD5+ "memory" cells, but in an unactivated state, and express the TCR-alpha/beta. In contrast to murine skin, only a very minor subpopulation of CD3+ cells in the human epidermis bears the TCR-gamma/delta. Epidermal TCs primarily are distributed along the rete ridges in the basal keratinocyte layer and are often in close apposition to Langerhans cells (LCs). These TCs were propagated from epidermal cell suspensions after stimulation with TC activating agents (Con A, rIL-1, rIL-2), then evaluated for phenotypic features and TCR diversity. Similar to the in situ situation, most were CD4-/CD8+/TCR-alpha/beta+. In addition, two cultures contained TCR- gamma/delta+ cells; one of these determined to be an adherent CD4-/CD8+ population. Epidermal TCs were significantly (p less than 0.0001) more abundant in the sole than in the other body regions examined (i.e., 40 vs. 7 CD3+ cells/linear centimeter of epidermis) and seemed to have a particular affinity for the acrosyringial epithelium of eccrine sweat ducts. Moreover, the sole usually contained a greater number of CD8+ relative to CD4+ TCs, whereas the epidermal CD4/CD8 ratio in the trunk and extremities was quite variable, although the trend also was towards a slightly larger percentage of CD8+ cells. Collectively, our data suggest that the volar epidermis has a unique microenvironment which is responsible for both the higher density of TCs, preferentially CD8+, and lower number of LCs. This study has not only provided evidence for significant regional variability in the human epidermal TC population of normal skin, but also strengthens the concept for skin-associated lymphoid tissues (SALT), whereby memory TCs recirculate back to the epidermis and interact with resident antigen-presenting cells (i.e., LC). PMID:2182763

  2. Epidermal cell death in frogs with chytridiomycosis

    PubMed Central

    Roberts, Alexandra A.; Skerratt, Lee F.; Berger, Lee

    2017-01-01

    Background Amphibians are declining at an alarming rate, and one of the major causes of decline is the infectious disease chytridiomycosis. Parasitic fungal sporangia occur within epidermal cells causing epidermal disruption, but these changes have not been well characterised. Apoptosis (planned cell death) can be a damaging response to the host but may alternatively be a mechanism of pathogen removal for some intracellular infections. Methods In this study we experimentally infected two endangered amphibian species Pseudophryne corroboree and Litoria verreauxii alpina with the causal agent of chytridiomycosis. We quantified cell death in the epidermis through two assays: terminal transferase-mediated dUTP nick end-labelling (TUNEL) and caspase 3/7. Results Cell death was positively associated with infection load and morbidity of clinically infected animals. In infected amphibians, TUNEL positive cells were concentrated in epidermal layers, correlating to the localisation of infection within the skin. Caspase activity was stable and low in early infection, where pathogen loads were light but increasing. In animals that recovered from infection, caspase activity gradually returned to normal as the infection cleared. Whereas, in amphibians that did not recover, caspase activity increased dramatically when infection loads peaked. Discussion Increased cell death may be a pathology of the fungal parasite, likely contributing to loss of skin homeostatic functions, but it is also possible that apoptosis suppression may be used initially by the pathogen to help establish infection. Further research should explore the specific mechanisms of cell death and more specifically apoptosis regulation during fungal infection. PMID:28168107

  3. Changes of epidermal thickness in vitiligo.

    PubMed

    Jung, Soo-Eun; Kang, Hee Young; Lee, Eun-So; Kim, You Chan

    2015-04-01

    The stratum corneum and epidermal pigmentation have protective roles against ultraviolet radiation. Because vitiligo skin lacks melanocytes and has no potential to produce pigment, some studies suggested that the epidermis in vitiligo skin is thicker than in normal skin. However, only a few studies investigated epidermal thickness changes in vitiligo, and some of these had relatively small sample sizes. Thus, this study aimed to compare epidermal thickness between vitiligo skin and adjacent normal-appearing skin in a large cohort. Photos of hematoxylin and eosin–stained slides of vitiligo skin and adjacent normal-appearing skin were taken under a microscope. The thicknesses of the stratum corneum, viable epidermis, and full epidermis were then measured by a computerized image analyzer. A total of 206 patients (412 sections) were included. There were significant differences between vitiligo skin and adjacent normal-appearing skin in the thickness of the stratum corneum (P = 0.009), viable epidermis (P = 0.001), and total epidermis (P = 0.001). An analysis comparing skin biopsied from a sun-exposed area versus a sun-protected area showed that the stratum corneum, viable epidermis, and total epidermis were significantly thicker in vitiligo skin than in normal-appearing skin in sun-exposed areas (P < 0.05), but not in sun-protected areas. We revealed that the epidermis was thicker in vitiligo skin than in normal-appearing skin, especially on sun-exposed skin, and that this may represent a photoprotective role compensating for absent pigmentation.

  4. Fatty aldehyde and fatty alcohol metabolism: review and importance for epidermal structure and function.

    PubMed

    Rizzo, William B

    2014-03-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal 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. © 2013.

  5. Human epidermal stem cells: Role in adverse skin reactions and carcinogenesis from radiation.

    PubMed

    Martin, Michèle T; Vulin, Adeline; Hendry, Jolyon H

    In human skin, keratinopoiesis is based on a functional hierarchy among keratinocytes, with rare slow-cycling stem cells responsible for the long-term maintenance of the tissue through their self-renewal potential, and more differentiated daughter progenitor cells actively cycling to permit epidermal renewal and turn-over every month. Skin is a radio-responsive tissue, developing all types of radiation damage and pathologies, including early tissue reactions such as dysplasia and denudation in epidermis, and later fibrosis in the dermis and acanthosis in epidermis, with the TGF-beta 1 pathway as a known master switch. Also there is a risk of basal cell carcinoma, which arises from epidermal keratinocytes, notably after oncogenic events in PTCH1 or TP53 genes. This review will cover the mechanisms of adverse human skin reactions and carcinogenesis after various types of exposures to ionizing radiation, with comparison with animal data when necessary, and will discuss the possible role of stem cells and their progeny in the development of these disorders. The main endpoints presented are basal cell intrinsic radiosensitivity, genomic stability, individual factors of risk, dose specific responses, major molecular pathways involved and the cellular origin of skin reactions and cancer. Although major advances have been obtained in recent years, the precise implications of epidermal stem cells and their progeny in these processes are not yet fully characterized. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Epidermal chalone and cyclic AMP: an in vivo study.

    PubMed

    Elgjo, K

    1975-01-01

    Water extracts of skin contain two factors that inhibit epidermal cell proliferation: one substance inhibits epidermal cells in the G2 phase (the epidermal G2 inhibitor), and another inhibits the transit of cells from the G1 phase into the S phase (the epidermal G1 inhibitor). Pretreatment of mice with a beta-receptor antagonist (propranolol) abolished the activity of the G2 inhibitor but not that of the G1 inhibitor. After pretreatment with both propranolol and a phosphodiesterase inhibitor (caffine)the G2 inhibitor had full effect. Cafine alone had a moderately inhibitory effect on epidermal G2 cells and enhanced the depressing effect of the G1 inhibitor on epidermal DNA synthesis. AMP level in epidermis to be active. Cyclic AMP is probably also involved in the regulation of the rate of transit of epidermal G1 cells into the S phase but the epidermal cyclic AMP level seems not to be so critical for the efficacy of the epidermal G2 inhibitor in epidermal cell differentiation.

  7. Use of human epidermal cells in the study of carcinogenesis

    SciTech Connect

    Kuroki, T.; Chida, K.; Hosomi, J.; Kondo, S. )

    1989-05-01

    Because of the importance of human cells, particularly human epithelial cells, in cancer research, we have studied certain phases or events of carcinogenesis using human epidermal cells in primary culture. (1) We found that human epidermal cells are capable of metabolizing benzo(a)pyrene. Large inter-individual variations are found in the basal and induced arylhydrocarbon-hydroxylase activities. (2) UV-induced unscheduled DNA synthesis was demonstrated in human epidermal cells on autoradiographs. We also found that DNA repair is defective in epidermal cells isolated from xeroderma pigmentosum by a new explant-outgrowth culture. (3) Human epidermal cells are unique in that there is a large number of binding sites to phorbol esters compared with mouse epidermal cells, but there is no down-regulation. Further, human epidermal cells show essentially negative responses to tumor promoters, i.e., no stimulation of DNA synthesis, sugar uptake, and no induction of ornithine decarboxylase activity. (4) Human epidermal cells contain 1.5 x 10(5) binding sites per cell for epidermal growth factor (EGF), whereas squamous cell carcinomas of skin and oral cavity have larger amounts of EGF receptors in the order of 10(6) per cell. (5) Based on the above results, we attempted to transform human epidermal cells by the treatment with chemical carcinogens, but until now no transformation was obtained. 16 references.

  8. Interaction between the TP63 and SHH pathways is an important determinant of epidermal homeostasis

    PubMed Central

    Chari, N S; Romano, R A; Koster, M I; Jaks, V; Roop, D; Flores, E R; Teglund, S; Sinha, S; Gruber, W; Aberger, F; Medeiros, L J; Toftgard, R; McDonnell, T J

    2013-01-01

    Deregulation of the hedgehog (HH) pathway results in overexpression of the GLI target BCL2 and is an initiating event in specific tumor types including basal cell carcinoma of the skin. Regulation of the HH pathway during keratinocyte differentiation is not well understood. We measured HH pathway activity in response to differentiation stimuli in keratinocytes. An upregulation of suppressor of fused (SUFU), a negative regulator of the HH pathway, lowered HH pathway activity and was accompanied by loss of BCL2 expression associated with keratinocyte differentiation. We used in vitro and in vivo models to demonstrate that ΔNp63α, a crucial regulator of epidermal development, activates SUFU transcription in keratinocytes. Increasing SUFU protein levels inhibited GLI-mediated gene activation in suprabasal keratinocytes and promoted differentiation. Loss of SUFU expression caused deregulation of keratinocyte differentiation and BCL2 overexpression. Using in vivo murine models, we also provide evidence of GLI-mediated regulation of the TP63 pathway. p63 expression appears essential to establish an optimally functioning HH pathway. These observations present a regulatory mechanism by which SUFU acts as an interacting node between the HH and TP63 pathways to mediate differentiation and maintain epidermal homeostasis. Disruption of this regulatory node can be an important contributor to multistep carcinogenesis. PMID:23686138

  9. [Evaluation of Fusarium spp. pathogenicity in plant and murine models].

    PubMed

    Forero-Reyes, Consuelo M; Alvarado-Fernández, Angela M; Ceballos-Rojas, Ana M; González-Carmona, Lady C; Linares-Linares, Melva Y; Castañeda-Salazar, Rubiela; Pulido-Villamarín, Adriana; Góngora-Medina, Manuel E; Cortés-Vecino, Jesús A; Rodríguez-Bocanegra, María X

    2017-10-05

    The genus Fusarium is widely recognized for its phytopathogenic capacity. However, it has been reported as an opportunistic pathogen in immunocompetent and immunocompromised patients. Thus, it can be considered a microorganism of interest in pathogenicity studies on different hosts. Therefore, this work evaluated the pathogenicity of Fusarium spp. isolates from different origins in plants and animals (murine hosts). Twelve isolates of Fusarium spp. from plants, animal superficial mycoses, and human superficial and systemic mycoses were inoculated in tomato, passion fruit and carnation plants, and in immunocompetent and immunosuppressed BALB/c mice. Pathogenicity tests in plants did not show all the symptoms associated with vascular wilt in the three plant models; however, colonization and necrosis of the vascular bundles, regardless of the species and origin of the isolates, showed the infective potential of Fusarium spp. in different plant species. Moreover, the pathogenicity tests in the murine model revealed behavioral changes. It was noteworthy that only five isolates (different origin and species) caused mortality. Additionally, it was observed that all isolates infected and colonized different organs, regardless of the species and origin of the isolates or host immune status. In contrast, the superficial inoculation test showed no evidence of epidermal injury or colonization. The observed results in plant and murine models suggest the pathogenic potential of Fusarium spp. isolates in different types of hosts. However, further studies on pathogenicity are needed to confirm the multihost capacity of this genus. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    PubMed Central

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

    2010-01-01

    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

  11. 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.

  12. Combining chemotherapy with epidermal growth factor receptor inhibition in advanced non-small cell lung cancer

    PubMed Central

    Leung, Linda; Loong, Herbert

    2012-01-01

    Treatment of advanced stage lung cancer is changing rapidly. With the new found knowledge on molecular targets such as the epidermal growth factor receptor (EGFR), effective therapy is now available in a selected population with the target mutation. Single-agent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a standard first-line therapy for patients with activating-EGFR mutation such as base-pair deletion in exon 19 or point mutation at exon 21. At the same time, this class of drugs may be combined with chemotherapy. Studies on the concurrent combination of chemotherapy and EGFR-TKI confirmed a lack of efficacy. A phase II study on sequential intercalated combination has demonstrated an improvement in progression-free survival (PFS), but this needs to be validated by the ongoing phase III study. The third approach is to combine EGFR-TKI as maintenance therapy after tumour response or stable disease to cytotoxic chemotherapy. Two phase III studies have shown improvement in PFS, but the use of biomarkers for the selection of maintenance therapy remains debatable. Cetuximab is a monoclonal antibody against EGFR and its combination with chemotherapy was shown to improve overall survival in an unselected population. A new biomarker using the H-score will help to select patients for this combination. PMID:22754591

  13. GBM heterogeneity as a function of variable epidermal growth factor receptor variant III activity

    PubMed Central

    Lindberg, Olle R.; McKinney, Andrew; Engler, Jane R.; Koshkakaryan, Gayane; Gong, Henry; Robinson, Aaron E.; Ewald, Andrew J.; Huillard, Emmanuelle; James, C. David; Molinaro, Annette M.; Shieh, Joseph T.; Phillips, Joanna J.

    2016-01-01

    Abnormal activation of the epidermal growth factor receptor (EGFR) due to a deletion of exons 2-7 of EGFR (EGFRvIII) is a common alteration in glioblastoma (GBM). While this alteration can drive gliomagenesis, tumors harboring EGFRvIII are heterogeneous. To investigate the role for EGFRvIII activation in tumor phenotype we used a neural progenitor cell-based murine model of GBM driven by EGFR signaling and generated tumor progenitor cells with high and low EGFRvIII activation, pEGFRHi and pEGFRLo. In vivo, ex vivo, and in vitro studies suggested a direct association between EGFRvIII activity and increased tumor cell proliferation, decreased tumor cell adhesion to the extracellular matrix, and altered progenitor cell phenotype. Time-lapse confocal imaging of tumor cells in brain slice cultures demonstrated blood vessel co-option by tumor cells and highlighted differences in invasive pattern. Inhibition of EGFR signaling in pEGFRHi promoted cell differentiation and increased cell-matrix adhesion. Conversely, increased EGFRvIII activation in pEGFRLo reduced cell-matrix adhesion. Our study using a murine model for GBM driven by a single genetic driver, suggests differences in EGFR activation contribute to tumor heterogeneity and aggressiveness. PMID:27738329

  14. 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

  15. Murine typhus in travelers returning from Indonesia.

    PubMed

    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.

  16. 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.

  17. The Role of p16(INK4a) Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer.

    PubMed

    D'Arcangelo, Daniela; Tinaburri, Lavinia; Dellambra, Elena

    2017-07-22

    The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16(INK4a) is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16(INK4a) governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development. Keratinocytes are equipped with several epigenetic enzymes and transcription factors that shape the gene expression signatures of different epidermal layers and allow dynamic and coordinated expression changes to finely balance keratinocyte self-renewal and differentiation. These factors converge their activity in the basal layer to repress p16(INK4a) expression, protecting cells from senescence, and preserving epidermal homeostasis and regeneration. Several stress stimuli may activate p16(INK4a) expression that orchestrates cell cycle exit and senescence response. In the present review, we discuss the role of p16(INK4a) regulators in human epidermal SC self-renewal, aging and cancer.

  18. Three-Dimensional Analysis of Cell Division Orientation in Epidermal Basal Layer Using Intravital Two-Photon Microscopy

    PubMed Central

    Nemoto, Tomomi

    2016-01-01

    Epidermal structures are different among body sites, and proliferative keratinocytes in the epidermis play an important role in the maintenance of the epidermal structures. In recent years, intravital skin imaging has been used in mammalian skin research for the investigation of cell behaviors, but most of these experiments were performed with rodent ears. Here, we established a non-invasive intravital imaging approach for dorsal, ear, hind paw, or tail skin using R26H2BEGFP hairless mice. Using four-dimensional (x, y, z, and time) imaging, we successfully visualized mitotic cell division in epidermal basal cells. A comparison of cell division orientation relative to the basement membrane in each body site revealed that most divisions in dorsal and ear epidermis occurred in parallel, whereas the cell divisions in hind paw and tail epidermis occurred both in parallel and oblique orientations. Based on the quantitative analysis of the four-dimensional images, we showed that the epidermal thickness correlated with the basal cell density and the rate of the oblique divisions. PMID:27657513

  19. Toxic epidermal necrolysis induced by lansoprazole.

    PubMed

    Fracaroli, Tainá Scalfoni; Miranda, Ludmilla Queirós; Sodré, João Luz; Chaves, Mário; Gripp, Alexandre

    2013-01-01

    Toxic epidermal necrolysis is a rare, severe cutaneous reaction, mostly caused by drugs. It affects the skin and mucous membranes, with involvement of more than 30% of body surface. We describe the case of a young woman, previously healthy, who developed skin detachment of more than 90% of the body surface 15 days after being administered lansoprazole for peptic disease. The treatment consisted in discontinuation of the drug involved and early administration of intravenous human immunoglobulin, which led to a satisfactory outcome of the case, substantiating the impact of early diagnosis and treatment on the morbidity and mortality of these patients.

  20. Toxic epidermal necrolysis induced by lansoprazole*

    PubMed Central

    Fracaroli, Tainá Scalfoni; Miranda, Ludmilla Queirós; Sodré, João Luz; Chaves, Mário; Gripp, Alexandre

    2013-01-01

    Toxic epidermal necrolysis is a rare, severe cutaneous reaction, mostly caused by drugs. It affects the skin and mucous membranes, with involvement of more than 30% of body surface. We describe the case of a young woman, previously healthy, who developed skin detachment of more than 90% of the body surface 15 days after being administered lansoprazole for peptic disease. The treatment consisted in discontinuation of the drug involved and early administration of intravenous human immunoglobulin, which led to a satisfactory outcome of the case, substantiating the impact of early diagnosis and treatment on the morbidity and mortality of these patients. PMID:23539016

  1. 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)

  2. Examining maintenance responsibilities.

    PubMed

    Lam, K C

    2001-06-01

    This paper has examined the important responsibilities of the two organisations involved in the provision of maintenance service for the vital building services in many of our highly serviced buildings. The issues raised could be put to beneficial use in both clients and maintenance providers. All in all, the clients should work closely with their maintenance providers. Engineering services in buildings will not perform satisfactorily and efficiently if both parties do not work together and understand the maintenance tasks based on a business partnering mode. Put forward is the view that the management of the activities involved in the operation and maintenance process is a "shared commitment/involvement" between the client and the maintenance provider. It is obvious that many factors can influence the continued effectiveness of a quality maintenance scheme set up by client and provider. Some of these factors are: Change in key personnel Updates in technology Amendments to engineering practice Implementation of legislative requirements Changes in operation by client or provider Change of use of building Passage of time These factors must be fully reviewed by both parties from time to time, and necessary actions taken. A cooperative team working relationship and improved communication should be fostered by the client and his provider for the best management of services maintenance. This arrangement will contribute to better building services systems with continuous improvement; improved value for clients and higher return for the maintenance provider.

  3. [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.

  4. 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

  5. Nasopharyngeal epidermal cyst in a dog.

    PubMed

    Ellison, G W; Donnell, R L; Daniel, G B

    1995-12-15

    Plain film radiography, magnetic resonance imaging, and histologic evaluation were used to diagnose nasopharyngeal epidermal cyst in a 12-year-old male Miniature Poodle with inspiratory stridor. The cyst was lined with stratified squamous epithelium, with variable keratinization. Most of the epithelium was well-differentiated and supported by a fibrovascular tissue separating it from underlying woven bone. One margin of the mass had a transition from stratified squamous to columnar respiratory epithelium. Other reported epidermal cysts in dogs have been confined to the middle ear or intracranial area. This case was unique, because the mass was located in the nasopharyngeal area, causing airway obstruction. This lesion was most likely acquired rather than congenital, because the dog had a history of middle ear inflammation, as well as bite wound trauma to the throat region. The mass was successfully removed by use of a transpalatal approach, and signs attributable to respiratory obstruction were alleviated. The dog had no abnormal clinical signs several months after the procedure.

  6. Estimation of age by epidermal image processing.

    PubMed

    Tatsumi, S; Noda, H; Sugiyama, S

    1999-12-01

    Small pieces of human precordial skin were obtained from 266 individuals during autopsy performed in Osaka Prefecture. The area from the stratum corneum to the stratum basale in a unit area of the epidermal cross-section was extracted as a segmented area of white image by image processing. The number of pixels surrounding this area was measured in individuals of various ages, and the age-associated changes were evaluated. The number of pixels around this binary image in the epidermal cross-section showed a strong correlation with age. The number tended to decrease with an increase in age in individuals aged 20 years and above, which could be closely approximated by an exponential function. A formula for estimating age was obtained as an inverse function of the number of pixels and age, and the accuracy of estimation using this formula was examined by comparing the estimated age with the actual age. Such age-associated changes in the epidermis were considered to be closely related with increased roughening of the stratum basale, flattening of dermal papillae, and a decreased percentage of the stratum granulosum per unit area of epidermis observed by light microscopy or scanning electron microscopy.

  7. 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

    2016-01-07

    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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Progressive Planned Maintenance.

    ERIC Educational Resources Information Center

    Lewis, Mary Jo; Jacobs, Richard S.

    A planned maintenance system, which was implemented at Washington State University (WSU), uniquely integrates functions of equipment inventory, scheduling, time reporting, project management, materials inventory, and billing. Management now has immediate access to equipment data, maintenance status, and costs. Staff requirements are readily…

  9. 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)…

  10. 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)…

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. [Targeted periodontal maintenance].

    PubMed

    Defleur, P; De Beule, F

    1995-01-01

    The goal of periodontal preventive cares known as "periodontal maintenance", are to maintain or to improve the periodontal situation after initial periodontal therapy. The inconveniences of a linear organisation of the maintenance are multiple. The aim of this work is to search a better way to organise the periodontal preventive cares and to offer a better service to the patients.

  16. 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…

  17. [Toxic epidermal necrolysis after treatment with oseltamivir: case report].

    PubMed

    Luna, Paula; Zuazaga, Marcela; Chede, Cecilia; Entin, Elías; Larralde, Margarita

    2010-06-01

    Toxic epidermal necrolysis is a rare acute and potentially life-threatening drug-related reaction. Osetalmivir is one of the drugs responsible for these reaction. We describe the case of a Down syndrome patient with toxic epidermal necrolysis previously treated with oseltamivir.

  18. Induction of epidermal cell fate in Arabidopsis shoots.

    PubMed

    Takada, Shinobu; Takada, Nozomi; Yoshida, Ayaka

    2013-11-01

    Land plants have evolved a cuticle-bearing epidermis to protect themselves from environmental stress and pathogen attack. Despite its important role, little is known about the molecular mechanisms regulating shoot epidermal cell identity. In a recent study, we found that the Arabidopsis thaliana ATML1 gene is possibly a master regulator of shoot epidermal cell fate. We revealed that ATML1 has the ability to confer shoot epidermis-related traits to non-epidermal cells of the seedlings. These data are consistent with the previous loss-of-function mutant analyses, which implied a positive role of ATML1 in epidermal cell differentiation. Importantly, ectopic epidermal cells induced in ATML1-overexpressing lines provide a novel tool to assess the intrinsic properties of epidermal cells and to study epistatic interactions among genes involved in epidermal/mesophyll differentiation. Using this system, we obtained data revealing that ATML1 negatively influenced mesophyll cell fate. In addition, we provided a working model of how division planes in epidermal cells are determined.

  19. [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.

  20. 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

  1. Epidermal cells adhere preferentially to type IV (basement membrane) collagen

    PubMed Central

    1979-01-01

    Epidermal cells from adult guinea pig skin attach and differentiate preferentially on substrates of type IV (basement membrane) collagen, compared to those of types I--III collagen. In contrast, guinea pig dermal fibroblasts attach equally well to all four collagen substrates. Fibronectin mediates the attachment of fibroblasts but not of epidermal cells to collagen. PMID:422650

  2. Application of Topical Acids Improves Atopic Dermatitis in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids

    PubMed Central

    Lee, Noo Ri; Lee, Hae-Jin; Yoon, Na Young; Kim, Donghye; Jung, Minyoung

    2016-01-01

    Background The acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD). Objective We performed an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions and to find out if the therapeutic effect of vinegar is attributable to its herbal contents, rather than its acidity. Methods Five groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity: vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and pH 3.5 hydrogen chloride (HCl) cream. Also, we have compared two groups of Ox-AD mice treated with pH 5.5 vehicle cream or pH 5.5 vinegar cream. Results Ox-AD mice treated with acidic creams exhibited fewer AD-like lesions, had significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference in eczema score, basal TEWL and SC hydration. Conclusion Application of topical acids, regardless of their source materials, inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model. PMID:27904267

  3. Effects of adenosine 5'-monophosphate on epidermal turnover.

    PubMed

    Furukawa, Fukumi; Kanehara, Shoko; Harano, Fumiki; Shinohara, Shigeo; Kamimura, Junko; Kawabata, Shigekatsu; Igarashi, Sachiyo; Kawamura, Mitsuaki; Yamamoto, Yuki; Miyachi, Yoshiki

    2008-10-01

    The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

  4. Discovery of a potent, selective, and orally active human epidermal growth factor receptor-2 sheddase inhibitor for the treatment of cancer.

    PubMed

    Yao, Wenqing; Zhuo, Jincong; Burns, David M; Xu, Meizhong; Zhang, Colin; Li, Yun-Long; Qian, Ding-Quan; He, Chunhong; Weng, Lingkai; Shi, Eric; Lin, Qiyan; Agrios, Costas; Burn, Timothy C; Caulder, Eian; Covington, Maryanne B; Fridman, Jordan S; Friedman, Steven; Katiyar, Kamna; Hollis, Gregory; Li, Yanlong; Liu, Changnian; Liu, Xiangdong; Marando, Cindy A; Newton, Robert; Pan, Max; Scherle, Peggy; Taylor, Nancy; Vaddi, Kris; Wasserman, Zelda R; Wynn, Richard; Yeleswaram, Swamy; Jalluri, Ravi; Bower, Michael; Zhou, Bing-Bing; Metcalf, Brian

    2007-02-22

    The design, synthesis, evaluation, and identification of a novel class of (6S,7S)-N-hydroxy-6-carboxamide-5-azaspiro[2.5]octane-7-carboxamides as the first potent and selective inhibitors of human epidermal growth factor receptor-2 (HER-2) sheddase is described. Several compounds were identified that possess excellent pharmacodynamic and pharmacokinetic properties and were shown to decrease tumor size, cleaved HER-2 extracellular domain plasma levels, and potentiate the effects of the humanized anti-HER-2 monoclonal antibody (trastuzumab) in vivo in a HER-2 overexpressing cancer murine xenograft model.

  5. Maintenance Process Strategic Analysis

    NASA Astrophysics Data System (ADS)

    Jasiulewicz-Kaczmarek, M.; Stachowiak, A.

    2016-08-01

    The performance and competitiveness of manufacturing companies is dependent on the availability, reliability and productivity of their production facilities. Low productivity, downtime, and poor machine performance is often linked to inadequate plant maintenance, which in turn can lead to reduced production levels, increasing costs, lost market opportunities, and lower profits. These pressures have given firms worldwide the motivation to explore and embrace proactive maintenance strategies over the traditional reactive firefighting methods. The traditional view of maintenance has shifted into one of an overall view that encompasses Overall Equipment Efficiency, Stakeholders Management and Life Cycle assessment. From practical point of view it requires changes in approach to maintenance represented by managers and changes in actions performed within maintenance area. Managers have to understand that maintenance is not only about repairs and conservations of machines and devices, but also actions striving for more efficient resources management and care for safety and health of employees. The purpose of the work is to present strategic analysis based on SWOT analysis to identify the opportunities and strengths of maintenance process, to benefit from them as much as possible, as well as to identify weaknesses and threats, so that they could be eliminated or minimized.

  6. Accumulation and activation of epidermal γδ T cells in a mouse model of chronic dermatitis is not required for the inflammatory phenotype.

    PubMed

    Sulcova, Jitka; Maddaluno, Luigi; Meyer, Michael; Werner, Sabine

    2015-09-01

    Chronic skin inflammation resulting from a defective epidermal barrier is a hallmark of atopic dermatitis (AD). We previously demonstrated that mice lacking FGF receptors 1 and 2 in keratinocytes (K5-R1/R2 mice) develop an AD-like chronic dermatitis as a result of an impaired epidermal barrier. Here, we show that γδ T cells, which rapidly respond to various insults, accumulate in the epidermis of K5-R1/R2 mice before the development of histological abnormalities. Their number and activation further increase as the phenotype progresses, most likely as a consequence of increased expression of Il-2 and Il-7 and the stress-induced proteins Rae-1, H60c, Mult1, PlexinB2, and Skint1. To determine the role of γδ T cells in the skin phenotype, we generated quadruple mutant K5-R1/-R2 mice lacking γδ T cells. Surprisingly, loss of γδ T cells did not or only marginally affect keratinocyte proliferation, epidermal thickness, epidermal barrier function, and accumulation and activation of different immune cells in the skin of K5-R1/R2 mice, possibly due to partial compensation by αβ T cells. These results demonstrate that γδ T cells do not contribute to the development or maintenance of chronic inflammation in response to a defect in the epidermal barrier.

  7. Toxic epidermal necrolysis (TEN) in elderly patients.

    PubMed

    Honari, S; Gibran, N S; Heimbach, D M; Gibbons, J; Pharmd; Cain, V; Engrav, L H

    2001-01-01

    Toxic epidermal necrolysis (TEN) is a severe exfoliative disease of the skin and mucous membranes that results in high mortality. As the elderly population increases, the number of elderly patients with TEN can also be expected to increase. Elderly patients with comparably sized burn wounds usually have a poor prognosis. Our purpose was to determine whether elderly TEN patients exhibit similarly high mortality. A retrospective review was conducted of 52 patients treated for TEN from October 1991 through September 1998. Eleven patients were older than 65 years. All patients were treated according to our TEN protocol. Eight of 11 patients recovered, and 3 died. The mean total body surface area (TBSA) involvement for the patients who recovered was 24%, compared with 66% for the nonsurvivors. The survival rate for elderly patients (73%) compares well with that for those younger than 65 years (89%). Therefore, we propose that we should be aggressive in treating elderly patients with TEN.

  8. 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.

  9. 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

  10. Epidermal growth factor receptor signaling in tissue

    SciTech Connect

    Shvartsman, Stanislav; Wiley, H. S.; Lauffenburger, Douglas A.

    2004-08-01

    Abstract: A peptide purified from the salivary gland of a mouse was shown few years ago to accelerate incisor eruption and eyelid opening in newborn mice, and was named epidermal growth factor (EGF). The members of this family of peptide growth factors had been identified in numerous physiological and pathological contexts. EGF binds to a cell surface EGF receptor, which induces a biochemical modification (phosphorylation) of the receptor's cytoplasmic tail. There is a growing consensus in the research community that, in addition to cellular and molecular studies, the dynamics of the EGFR network and its operation must be examined in tissues. A key challenge is to integrate the existing molecular and cellular information into a system-level description of the EGFR network at the tissue and organism level. In this paper, the two examples of EGFR signaling in tissues are described, and the recent efforts to model EGFR autocrine loops, which is a predominant mode of EGFR activation in vivo, are summarized.

  11. Micropatterned dermal-epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis.

    PubMed

    Clement, Amanda L; Moutinho, Thomas J; Pins, George D

    2013-12-01

    Although tissue engineered skin substitutes have demonstrated some clinical success for the treatment of chronic wounds such as diabetic and venous ulcers, persistent graft take and stability remain concerns. Current bilayered skin substitutes lack the characteristic microtopography of the dermal-epidermal junction that gives skin enhanced mechanical stability and creates cellular microniches that differentially promote keratinocyte function to form skin appendages and enhance wound healing. We developed a novel micropatterned dermal-epidermal regeneration matrix (μDERM) which incorporates this complex topography and substantially enhances epidermal morphology. Here, we describe the use of this three-dimensional (3-D) in vitro culture model to systematically evaluate different topographical geometries and to determine their relationship to keratinocyte function. We identified three distinct keratinocyte functional niches: the proliferative niche (narrow geometries), the basement membrane protein synthesis niche (wide geometries) and the putative keratinocyte stem cell niche (narrow geometries and corners). Specifically, epidermal thickness and keratinocyte proliferation is significantly (p<0.05) increased in 50 and 100 μm channels while laminin-332 deposition is significantly (p<0.05) increased in 400 μm channels compared to flat controls. Additionally, β1(bri)p63(+) keratinocytes, putative keratinocyte stem cells, preferentially cluster in channel geometries (similar to clustering observed in native skin) compared to a random distribution on flats. This study identifies specific target geometries to enhance skin regeneration and graft performance. Furthermore, these results suggest the importance of μDERM microtopography in designing the next generation of skin substitutes. Finally, we anticipate that 3-D organotypic cultures on μDERMS will provide a novel tissue engineered skin substitute for in vitro investigations of skin morphogenesis, wound healing and

  12. Infant epidermal skin physiology: adaptation after birth.

    PubMed

    Fluhr, J W; Darlenski, R; Lachmann, N; Baudouin, C; Msika, P; De Belilovsky, C; Hachem, J-P

    2012-03-01

    Functional and structural skin adaptation is a dynamic process which starts immediately after birth in humans and in mammalian skin in general. This adjustment to the extrauterine dry environment is accomplished in the first year of postnatal life of humans. To assess the dynamic changes in vivo after birth in the molecular composition and skin physiology parameters compared with older children and adults. The molecular composition of the stratum corneum (SC) and the water profile were investigated noninvasively by in vivo Raman confocal microscopy as a function of depth. Functional parameters including transepidermal water loss (characterizing epidermal permeability barrier), capacitance (as an indirect parameter for SC hydration) and skin surface pH were assessed noninvasively. The measurements were performed in 108 subjects divided into six age groups: full-term newborns (1-15 days), babies aged 5-6 weeks, babies aged 6±1 months, children aged 1-2 years, children aged 4-5 years and adults aged 20-35 years. We showed that skin acidification is still under development during the first weeks of life. While the basal epidermal barrier is competent immediately after birth, the SC is less hydrated in the first 2 weeks of postnatal life. Similar continuous decreasing water content towards the surface for all age groups was observed, whereas this gradient was lower for the newborns. Dynamic changes in the amounts of the natural moisturizing factor constituents were revealed in the period of infancy. We demonstrated the relation of formation of an acidic pH as well as underlying mechanisms in the induction of a fully hydrated SC over the first weeks of human life as a dynamic functional adaptation. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  13. Characterization of chicken epidermal dendritic cells

    PubMed Central

    Igyártó, Botond-Zoltán; Lackó, Erzsébet; Oláh, Imre; Magyar, Attila

    2006-01-01

    It has been known for 15 years that the chicken epidermis contains ATPase+ and major histocompatibility complex class II-positive (MHCII+) dendritic cells. These cells were designated as Langerhans cells but neither their detailed phenotype nor their function was further investigated. In the present paper we demonstrate a complete overlapping of ATPase, CD45 and vimentin staining in all dendritic cells of the chicken epidermis. The CD45+ ATPase+ vimentin+ dendritic cells could be divided into three subpopulations: an MHCII+ CD3– KUL01+ and 68.1+ (monocyte-macrophage subpopulation markers) subpopulation, an MHCII– CD3– KUL01– and 68.1– subpopulation and an MHCII– CD3+ KUL01– and 68.1– subpopulation. The first population could be designated as chicken Langerhans cells. The last population represents CD4– CD8– T-cell receptor-αβ– and -γδ– natural killer cells with cytoplasmic CD3 positivity. The epidermal dendritic cells have a low proliferation rate as assessed by bromodeoxyuridine incorporation. Both in vivo and in vitro experiments showed that dendritic cells could be mobilized from the epidermis. Hapten treatment of epidermis resulted in the decrease of the frequency of epidermal dendritic cells and hapten-loaded dendritic cells appeared in the dermis or in in vitro culture of isolated epidermis. Hapten-positive cells were also found in the so-called dermal lymphoid nodules. We suggest that these dermal nodules are responsible for some regional immunological functions similar to the mammalian lymph nodes. PMID:16889640

  14. Bricks and mortar of the epidermal barrier.

    PubMed

    Nemes, Z; Steinert, P M

    1999-03-31

    A specialized tissue type, the keratinizing epithelium, protects terrestrial mammals from water loss and noxious physical, chemical and mechanical insults. This barrier between the body and the environment is constantly maintained by reproduction of inner living epidermal keratinocytes which undergo a process of terminal differentiation and then migrate to the surface as interlocking layers of dead stratum corneum cells. These cells provide the bulwark of mechanical and chemical protection, and together with their intercellular lipid surroundings, confer water-impermeability. Much of this barrier function is provided by the cornified cell envelope (CE), an extremely tough protein/lipid polymer structure formed just below the cytoplasmic membrane and subsequently resides on the exterior of the dead cornified cells. It consists of two parts: a protein envelope and a lipid envelope. The protein envelope is thought to contribute to the biomechanical properties of the CE as a result of cross-linking of specialized CE structural proteins by both disulfide bonds and N(epsilon)-(gamma-glutamyl)lysine isopeptide bonds formed by transglutaminases. Some of the structural proteins involved include involucrin, loricrin, small proline rich proteins, keratin intermediate filaments, elafin, cystatin A, and desmosomal proteins. The lipid envelope is located on the exterior of and covalently attached by ester bonds to the protein envelope and consists of a monomolecular layer of omega-hydroxyceramides. These not only serve of provide a Teflon-like coating to the cell, but also interdigitate with the intercellular lipid lamellae perhaps in a Velcro-like fashion. In fact the CE is a common feature of all stratified squamous epithelia, although its precise composition, structure and barrier function requirements vary widely between epithelia. Recent work has shown that a number of diseases which display defective epidermal barrier function, generically known as ichthyoses, are the

  15. 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.

  16. Factors Influencing Army Maintenance

    DTIC Science & Technology

    1989-01-01

    ARI Research Note 89-11 (N 00 Factors Influencing Army Maintenance LOloD Debra C. Evans and J. Thomas Roth Applied Science Associates, Inc. for...1.2.7 .2.7.C.1 11. TITLE (Include Security ClassifIcarIon) Factors Influencing Army Maintenance i2. FERSONAL AuTtiOR(S) Evans, Debra C., and Roth, J...y • ’ Factors and variables that influence maintenance for systems and related manpower, per- sonnel, and training (MPT) characteristics were

  17. General Healthcare Maintenance of IBD

    MedlinePlus

    ... Resources > General Healthcare Maintenance Go Back General Healthcare Maintenance Email Print + Share It is important to continue ... Bowel Diseases. September 2009, 1399-1409 Health Care Maintenance Chart YEAR PPD (Tuberculosis skin test) Vaccinations Hepatitis ...

  18. Direct identification of residues of the epidermal growth factor receptor in close proximity to the amino terminus of bound epidermal growth factor.

    PubMed Central

    Woltjer, R L; Lukas, T J; Staros, J V

    1992-01-01

    We have recently developed a kinetically controlled, step-wise affinity cross-linking technique for specific, high-yield, covalent linkage of murine epidermal growth factor (mEGF) via its N terminus to the EGF receptor. EGF receptor from A431 cells was cross-linked to radiolabeled mEGF (125I-mEGF) by this technique and the 125I-mEGF-receptor complex was purified and denatured. Tryptic digestion of this preparation gave rise to a unique radiolabeled peptide that did not comigrate with trypsin-treated 125I-mEGF in SDS/Tricine gels but that could be immunoprecipitated with antibodies to mEGF. The immunoprecipitated peptide was isolated by electrophoresis in SDS/Tricine gels, eluted, and sequenced. The sequence was found to correspond to that of a tryptic peptide of the EGF receptor beginning with Gly-85, which is in domain I, a region N terminal to the first cysteine-rich region of the receptor. Selective loss of signal in the 17th sequencing cycle suggests that the point of attachment of N-terminally modified 125I-mEGF to the receptor is Tyr-101. The data presented here provide identification by direct protein microsequencing of a site of interaction of EGF and the EGF receptor. Images PMID:1380167

  19. 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.

  20. MCA Inflight Maintenance

    NASA Image and Video Library

    2011-07-06

    ISS028-E-014395 (6 July 2011) --- NASA astronaut Ron Garan, Expedition 28 flight engineer, performs in-flight maintenance on the Mass Constituents Analyzer (MCA) in the Destiny laboratory of the International Space Station.

  1. 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)

  2. 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)

  3. 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)

  4. Automated preventive maintenance program

    NASA Technical Reports Server (NTRS)

    Cea, E. J.; Grieger, T. H.

    1971-01-01

    Maintenance program which is concise and inexpensive to operate adapts to almost any system that has a FORTRAN compiler. Program operates on a stored data base with an output consisting of scheduling information and various management reports.

  5. Timpani Repair and Maintenance.

    ERIC Educational Resources Information Center

    Combs, F. Michael

    1980-01-01

    Rather than focusing on specific brands of timpani, these guidelines for repair cover mechanical problems of a general nature: pedals, dents, unclear tone, and squeaking. Preventive maintenance is discussed. (Author/SJL)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. The Deferred Maintenance Dilemma.

    ERIC Educational Resources Information Center

    Medlin, E. Lander

    2003-01-01

    Discusses the hazards of the trend toward accumulated deferred maintenance in higher education and offers advice on tying facilities needs and issues to the core strategies and goals of the institution. (EV)

  12. Barrett during TVIS maintenance

    NASA Image and Video Library

    2009-04-21

    ISS019-E-008767 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  13. Barrett during TVIS maintenance

    NASA Image and Video Library

    2009-04-21

    ISS019-E-008750 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  14. Barrett during TVIS maintenance

    NASA Image and Video Library

    2009-04-21

    ISS019-E-008764 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  15. Barrett during TVIS maintenance

    NASA Image and Video Library

    2009-04-21

    ISS019-E-008752 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  16. TVIS Inflight Maintenance

    NASA Image and Video Library

    2011-07-01

    ISS028-E-013757 (1 July 2011) --- Russian cosmonaut Andrey Borisenko, Expedition 28 commander, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  17. SPHERES Maintenance Run

    NASA Image and Video Library

    2016-06-30

    iss048e017435 (6/30/2016) --- Commander Jeff Williams monitors bowling ball-sized internal satellites known as SPHERES (Synchronized Position Hold, Engage, Reorient, Experimental Satellites) during a maintenance run in the Japanese Kibo Laboratory Module.

  18. 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.

  19. Reliability-Centered Maintenance

    DTIC Science & Technology

    1978-12-29

    ANALYSIS 425 D-3 INFORMATION SCIENCi AND DECISION ANALYSIS 427 D-4 MAINTENANCE THEORY AND PHILOSOPHY 430 D-5 MAINTENANCE APPLUCATIONS 436 D-6 A GUIDE...on-condition task. Unfor- tunately it is usually beyond human capability to look at a used part and determine what its likelihood of failure will be...be found in serviceable units that are removed at some specified age limit, but -t is generally beyond human capability to estimate from this early

  20. Studies on the conservation of epidermal specificies of skin and certain mucosas in adult mammals.

    PubMed

    Billingham, R E; Silvers, W K

    1967-03-01

    To determine whether the factor(s) responsible for the conservation of epidermal specificities in adult guinea pigs and hamsters resides in the germinal layer of the epidermis or in the dermis, thin grafts of skin, possessing qualitatively distinct regional characteristics, were separated into their superficial epidermal and dermal components with the aid of trypsin. Dermis of one type was combined with epidermis of another to produce "recombinant" grafts which were then transplanted to small, full thickness cutaneous sites on the thorax of geneticaily compatible hosts. A variant of this procedure involved transplanting sheets of superficial epidermis of various types to shallow split thickness recipient areas in the skin of the thorax. All grafts were maintained for 100 days before they were excised and examined histologically. The results indicate that, whereas the dermis determines the kind of epidermis produced in recombinant grafts involving the ear, the sole of the foot, and the trunk, this is not the case in recombinants which include tongue, esophageal, or cheek pouch epithelia. The one exception to this occurred when tongue or esophagus epithelia were transplanted to split thickness beds in trunk skin. Here they appeared to produce an epidermis characteristic of their new location. It is believed that this exception is probably due to the fact that the native follicular epidermis present in trunk dermis made such a substantial contribution to the new superficial epidermis that it behaved overtly as body skin epidermis. Taken together, these results suggest that basal layer cells of the superficial epidermis of sole of foot skin, ear skin, and the hair-bearing skin of the general integument behave as if they are equipotential, and that in adult life maintenance of these particular epidermal specificities is the outcome of persistent specific inductive stimuli from the underlying dermis. The results of subsidiary experiments are reported which indicate that

  1. Psoriasiform architecture of murine epidermis overlying human psoriatic dermis transplanted onto SCID mice.

    PubMed

    Boehncke, W H; Sterry, W; Hainzl, A; Scheffold, W; Kaufmann, R

    1994-01-01

    Preliminary observations in a xenogeneic SCID mouse transplantation model indicated that murine epidermis overgrows human dermis from psoriatic skin but not that form normal skin. To investigate the effect of peripheral blood mononuclear cells on the differentiation of murine keratinocytes, we transplanted involved and uninvolved full-thickness skin from patients with psoriasis onto SCID mice and followed this with repeated subcutaneous injections of cells suspended in patient serum. After 6 weeks grafts were analysed morphologically and immunohistochemically. The epidermis in grafts from clinically uninvolved skin appeared normal. The persistence of a psoriasiform epidermis was noted in all grafts from affected sites despite a lack of lymphocytic infiltration. Staining for human and mouse MHC class I antigens revealed the murine origin of keratinocytes forming the psoriasiform epidermis, while the human dermis was retained. Our observations indicate that the defect underlying the pathogenesis of psoriasis is most likely located in the dermal rather than the epidermal compartment. This xenogeneic transplantation model may be useful for future studies of the pathogenesis and treatment of psoriasis.

  2. FGD maintenance guidelines. Volume 2: FGD maintenance information. Final report

    SciTech Connect

    Davidson, L.N.; Miller, G.P.; Wedig, C.P.

    1986-07-01

    The ''FGD Maintenance Guidelines'' was written to fill the need for maintenance information that applies specifically to flue gas desulfurization (FGD) systems. Previously there was no single source of data describing FGD maintenance. Usually maintenance managers relied on suppliers' operating and maintenance manuals, past FGD experience, or procedures from other areas of a power plant. There are two volumes in the Guidelines intended to assist utility personnel in planning and performing maintenance for FGD systems. Different aspects of maintenance are emphasized in each volume. Volume 1, FGD Maintenance Programs, provides guidance for supervisory personnel involved in planning maintenance. It describes the utility industry's experience with FGD maintenance programs, a procedure for organizing and managing maintenance programs, and ways to design FGD systems for maintainability. The section about implementing a maintenance program contains a detailed example to illustrate the procedure, based on experience of an actual operating FGD system. Volume 2, FGD Maintenance Information, has practical information, useful in understanding FGD systems and their maintenance needs. It describes the major types of FGD systems operating in the US and typical maintenance associated with each. Also, in this volume, there is information about maintenance needs and procedures for the most common types of FGD equipment. 21 refs., 48 figs., 3 tabs.

  3. The mysterious human epidermal cell cycle, or an oncogene-induced differentiation checkpoint

    PubMed Central

    Gandarillas, Alberto

    2012-01-01

    Fifteen years ago, we reported that proto-oncogene MYC promoted differentiation of human epidermal stem cells, a finding that was surprising to the MYC and the skin research communities. MYC was one of the first human oncogenes identified, and it had been strongly associated with proliferation. However, it was later shown that MYC could induce apoptosis under low survival conditions. Currently, the notion that MYC promotes epidermal differentiation is widely accepted, but the cell cycle mechanisms that elicit this function remain unresolved. We have recently reported that keratinocytes respond to cell cycle deregulation and DNA damage by triggering terminal differentiation. This mechanism might constitute a homeostatic protection face to cell cycle insults. Here, I discuss recent and not-so-recent evidence suggesting the existence of a largely unexplored oncogene-induced differentiation response (OID) analogous to oncogene-induced apoptosis (OIA) or senescence (OIS). In addition, I propose a model for the role of the cell cycle in skin homeostasis maintenance and for the dual role of MYC in differentiation. PMID:23114621

  4. Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation.

    PubMed

    Chidgey, M; Brakebusch, C; Gustafsson, E; Cruchley, A; Hail, C; Kirk, S; Merritt, A; North, A; Tselepis, C; Hewitt, J; Byrne, C; Fassler, R; Garrod, D

    2001-11-26

    The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation.

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

    PubMed

    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

    2011-02-01

    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.

  6. Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation

    PubMed Central

    Chidgey, Martyn; Brakebusch, Cord; Gustafsson, Erika; Cruchley, Alan; Hail, Chris; Kirk, Sarah; Merritt, Anita; North, Alison; Tselepis, Chris; Hewitt, Jane; Byrne, Carolyn; Fassler, Reinhard; Garrod, David

    2001-01-01

    The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation. PMID:11714727

  7. Generation of mesenchymal stem cell lines from murine bone marrow.

    PubMed

    Sreejit, P; Dilip, K B; Verma, R S

    2012-10-01

    Mesenchymal stem cells (MSC), because of their multipotency and ease of purification and amplification, are an ideal stem cell source for cell therapies. Bone-marrow-derived stem cells (BMSC) can be used to develop MSC-like immortalized cell lines with large proliferation and differentiation potentialities. Their immortalized status prevents the maintenance of MSC function and characters; this can be negated by modifying the isolation and maintenance protocol. Adult murine BMSC were isolated and maintained in media without additional growth factors together with passage-dependent reseeding following trypsinization. Cells maintained over 25 passages were considered as putative cell lines and characterized. The phenotypic and genotypic characteristics and multilineage differentiation potential of the cells were assessed by morphological, phenotypic, and molecular assays at various passages. The putative BMSC cell lines showed the characteristics of MSC and were able to maintain these characteristics, even after immortalization. The phenotypic data demonstrated difference among two cell lines; this was further validated by the difference in their multilineage differentiation potential following specific induction. More importantly, no changes were observed in the genotypic level in comparison with control cells, even after more than 50 passages. Our protocol thus advances the isolation and maintenance of BMSC and the development of putative BMSC cell lines that maintain characteristics of MSC, including multilineage differentiation potential, after more than 40 passages.

  8. Differing antidepressant maintenance methodologies.

    PubMed

    Safer, Daniel J

    2017-10-01

    The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

  9. Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

    PubMed Central

    Seneschal, Julien; Clark, Rachael A.; Gehad, Ahmed; Baecher-Allan, Clare M.; Kupper, Thomas S.

    2013-01-01

    Recent discoveries indicate that the skin of a normal individual contains 10-20 billion resident memory T cells ( which include various T helper, T cytotoxic, and T regulatory subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both in vitro and in vivo, resting epidermal Langerhan cells (LC) selectively and specifically induced the activation and proliferation of skin resident regulatory T cells (Treg), a minor subset of skin resident memory T cells. In the presence of foreign pathogen, however, the same LC activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells activation. These underappreciated properties of LC: namely maintenance of tolerance in normal skin, and activation of protective skin resident memory T cells upon infectious challenge, help clarify the role of LC in skin. PMID:22560445

  10. Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture

    SciTech Connect

    Gantt, R.; Sanford, K.K.; Parshad, R.; Price, F.M.; Peterson, W.D. Jr.; Rhim, J.S.

    1987-03-01

    A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containing the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.

  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. Fatal toxic epidermal necrolysis associated with minoxidil.

    PubMed

    Karaoui, Lamis R; Chahine-Chakhtoura, Corinne

    2009-04-01

    Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27-31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this

  13. 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.

  14. "Cut-and-paste" manufacture of multiparametric epidermal electronic systems

    NASA Astrophysics Data System (ADS)

    Lu, Nanshu; Yang, Shixuan; Wang, Pulin

    2016-05-01

    Epidermal electronics is a class of noninvasive and unobstructive skin-mounted, tattoo-like sensors and electronics capable of vital sign monitoring and establishing human-machine interface. The high cost of manpower, materials, vacuum equipment, and photolithographic facilities associated with its manufacture greatly hinders the widespread use of disposable epidermal electronics. Here we report a cost and time effective, completely dry, benchtop "cut-and-paste" method for the freeform and portable manufacture of multiparametric epidermal sensor systems (ESS) within minutes. This versatile method works for all types of thin metal and polymeric sheets and is compatible with any tattoo adhesives or medical tapes. The resulting ESS are multimaterial and multifunctional and have been demonstrated to noninvasively but accurately measure electrophysiological signals, skin temperature, skin hydration, as well as respiratory rate. In addition, planar stretchable coils exploiting double-stranded serpentine design have been successfully applied as wireless, passive epidermal strain sensors.

  15. Building Maintenance, Management, and Budgeting.

    ERIC Educational Resources Information Center

    Pawsey, M. R.

    1982-01-01

    Australian methods and formulas for funding building maintenance and management are outlined and found to be haphazard. Discussed are: ultimate costs of deferred maintenance, major plant replacements, life cycle costing, types of maintenance programs (including full preventive maintenance), use of computer programs for planning, and organization…

  16. Building Maintenance, Management, and Budgeting.

    ERIC Educational Resources Information Center

    Pawsey, M. R.

    1982-01-01

    Australian methods and formulas for funding building maintenance and management are outlined and found to be haphazard. Discussed are: ultimate costs of deferred maintenance, major plant replacements, life cycle costing, types of maintenance programs (including full preventive maintenance), use of computer programs for planning, and organization…

  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. Verrucous Epidermal Nevus - a misleading diagnosis for 28 years.

    PubMed

    Ocampo-Garza, Jorge; Di Chiacchio, Nilton Gioia; Haneke, Eckart; Di Chiacchio, Nilton; Noriega, Leandro Fonseca

    2017-09-19

    Epidermal nevi (EN) are hamartomas of the skin that result from mosaic post-zygotic mutations. There are several variants of EN, the verrucous epidermal nevus (VEN) being the most common. EN can be further subdivided into epidermolytic and nonepidermolytic, important since in contrast with nonepidermolytic EN, epidermolytic EN occurs sporadically (not heritable), and it is not associated with extracutaneous abnormalities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. The discovery of epidermal tight junctions.

    PubMed

    Ozawa, Toshiyuki; Sugawara, Koji; Tsuruta, Daisuke

    2014-06-01

    It was previously thought that the skin barrier is composed singly by the stratum corneum. However, this concept was overturned by the report of Tsukita's group in 2002. They convinced us that tight junctions exist in the stratum granulosum of the epidermis, with the constituent proteins being occludin, claudin-1 and claudin-4. However, more than 30 years before this, Hashimoto et al. described the possible existence of tight junctions in the epidermis in 'Intercellular spaces of the human epidermis as demonstrated with lanthanum' in 1971. Dr. Hashimoto observed lanthanum nitrate-injected human skin by electron microscopy. He discovered that the injected lanthanum penetrated the intercellular spaces of the basal and spinous layers of the epidermis and then moved towards the skin surface until penetration was halted in the granular cell layer near the stratum corneum. He described the cell-to-cell adhesion structures that blocked the movement of lanthanum as 'truly tight junctions'. Thus, this was the first description of the existence of tight junctions in the epidermis. However, the presence of these structures was denied by others and was forgotten. Thanks to the discovery of claudin, the existence of tight junctions between epidermal keratinocytes was finally confirmed. It is interesting that Hashimoto's finding was eventually proved to be correct three decades later as a result of progress in molecular biology. This article encourages us to recognize the importance of careful observation in the molecular biology era. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. 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.

  1. 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

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

    PubMed

    Esquirol Caussa, Jordi; Herrero Vila, Elisabeth

    2015-10-05

    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.

  3. 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.

  4. Ctip2 is a dynamic regulator of epidermal proliferation and differentiation by integrating EGFR and Notch signaling

    PubMed Central

    Zhang, Ling-juan; Bhattacharya, Shreya; Leid, Mark; Ganguli-Indra, Gitali; Indra, Arup K.

    2012-01-01

    Summary Epidermal morphogenesis results from a delicate balance between keratinocyte proliferation and differentiation, and this balance is perturbed upon deletion of transcription factor Ctip2. Here we demonstrate that Ctip2, in a cell autonomous manner, controls keratinocyte proliferation and cytoskeletal organization, and regulates the onset and maintenance of differentiation in keratinocytes in culture. Ctip2 integrates keratinocyte proliferation and the switch to differentiation by directly and positively regulating EGFR transcription in proliferating cells and Notch1 transcription in differentiating cells. In proliferative cells, the EGFR promoter is occupied by Ctip2, whereas Ctip2 is only recruited to the Notch1 promoter under differentiating conditions. Activation of EGFR signaling downregulates Ctip2 at the transcript level, whereas high calcium signaling triggers SUMOylation, ubiquitination and proteasomal degradation of Ctip2 at the protein level. Together, our findings demonstrate a novel mechanism(s) of Ctip2-mediated, coordinated control of epidermal proliferation and terminal differentiation, and identify a pathway of negative feedback regulation of Ctip2 during epidermal development. PMID:23015591

  5. 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.

  6. Roles of transient receptor potential proteins (TRPs) in epidermal keratinocytes.

    PubMed

    Denda, Mitsuhiro; Tsutsumi, Moe

    2011-01-01

    Epidermal keratinocytes are the epithelial cells of mammalian skin. At the basal layer of the epidermis, these cells proliferate strongly, and as they move towards the skin surface, differentiation proceeds. At the uppermost layer of the epidermis, keratinocytes undergo apoptosis and die, forming a thin, water-impermeable layer called the stratum corneum. Peripheral blood vessels do not reach the epidermis, but peripheral nerve fibers do penetrate into it. Until recently, it was considered that the main role of epidermal keratinocytes was to construct and maintain the water-impermeable barrier function. However, since the functional existence of TRPV1, which is activated by heat and low pH, in epidermal keratinocytes was identified, our understanding of the role of keratinocytes has changed enormously. It has been found that many TRP channels are expressed in epidermal keratinocytes, and play important roles in differentiation, proliferation and barrier homeostasis. Moreover, because TRP channels expressed in keratinocytes have the ability to sense a variety of environmental factors, such as temperature, mechanical stress, osmotic stress and chemical stimuli, epidermal keratinocytes might form a key part of the sensory system of the skin. The present review deals with the potential roles of TRP channels expressed in epidermal keratinocytes and focuses on the concept of the epidermis as an active interface between the body and the environment.

  7. 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

  8. Autologous epidermal cell suspension: A promising treatment for chronic wounds.

    PubMed

    Zhao, Hongliang; Chen, Yan; Zhang, Cuiping; Fu, Xiaobing

    2016-02-01

    Chronic wounds have become an increasing medical and economic problem of aging societies because they are difficult to manage. Skin grafting is an important treatment method for chronic wounds, which are refractory to conservative therapy. The technique involving epidermal cell suspensions was invented to enable the possibility of treating larger wounds with only a small piece of donor skin. Both uncultured and cultured autologous epidermal cell suspensions can be prepared and survive permanently on the wound bed. A systematic search was conducted of EMBASE, Cochrane Library, PubMed and web of science by using Boolean search terms, from the establishment of the database until May 31, 2014. The bibliographies of all retrieved articles in English were searched. The search terms were: (epithelial cell suspension OR keratinocyte suspension) and chronic and wound. From the included, 6 studies are descriptive interventions and discussed the use of autologous keratinocyte suspension to treat 61 patients' chronic wound. The various methods of preparation of epidermal cell suspension are described. The advantages and shortcomings of different carriers for epidermal cell suspensions are also summarised. Both uncultured and cultured autologous epidermal cell suspensions have been used to treat chronic wounds. Although the limitations of these studies include the small number of patient populations with chronic wounds and many important problems that remain to be solved, autologous epidermal cell suspension is a promising treatment for chronic wounds. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  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. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer.

    PubMed

    Minami, Seigo; Kijima, Takashi

    2015-01-01

    Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy.

  11. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

    PubMed Central

    Minami, Seigo; Kijima, Takashi

    2015-01-01

    Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy

  12. 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

  13. Baffle maintenance apparatus

    SciTech Connect

    Genter, J. B.; Quinn, G. J.; Shields, E. P.; Thomas, B. S.; Winkler, C. J.

    1983-12-20

    The baffle maintenance apparatus comprises a peening apparatus mounted on a movable carriage for reducing the width of a gap between two adjacent baffle plates in a nuclear reactor. The peening apparatus comprises an hydraulic hammer mounted on a pivotable plate that is capable of being positioned in proper relationship to the baffle plate for reducing the gap therebetween. The baffle maintenance apparatus may also comprise a gauging mechanism mounted on the carriage for determining the width of the gap between the baffle plates.

  14. 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.

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

    PubMed

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

    2013-03-01

    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 endothelin-1 (EDN1) in murine epidermis (EDN1(ep-/-) ) 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 ultraviolet B (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 EDN1(ep-/-) mice. Altogether, the present studies establish an essential role of EDN1 in epidermal keratinocytes to mediate UV-induced melanocyte homeostasis in vivo. © 2012 John Wiley & Sons A/S.

  16. 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.

  17. 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,…

  18. Horticulture: Grounds Maintenance Employee.

    ERIC Educational Resources Information Center

    Sims, James; And Others

    The unit of individualized learning activities is designed to provide training in grounds maintenance. The materials in the unit are divided into two sections. The developmental or preliminary phase (15 pages) is for use by the instructor and includes brief descriptions of the job and of the student population, along with listings of the specific…

  19. 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…

  20. 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,…

  1. 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…

  2. 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.

  3. 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)

  4. 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…

  5. 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)

  6. 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…

  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…

  8. 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…

  9. 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,…

  10. 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…

  11. Playground Inspection & Maintenance.

    ERIC Educational Resources Information Center

    Leeds, Gerard

    People today demand a safer work environment and a safer play environment for children. Accidents such as broken arms are no longer accepted as an inevitable part of growing up. This paper presents recommendations for the maintenance of safe playground areas and equipment, covering three main areas: (1) inspections, which should follow a specified…

  12. 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…

  13. 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,…

  14. Wakata during TVIS maintenance

    NASA Image and Video Library

    2009-04-21

    ISS019-E-008758 (21 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  15. Wakata during TVIS maintenance

    NASA Image and Video Library

    2009-04-21

    ISS019-E-008754 (21 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  16. TVIS Inflight Maintenance

    NASA Image and Video Library

    2011-07-01

    ISS028-E-013758 (1 July 2011) --- Russian cosmonauts Sergei Volkov, Expedition 28 flight engineer; and Andrey Borisenko (mostly out of frame at left), commander, perform in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

  17. Reiter performs TVIS maintenance

    NASA Image and Video Library

    2006-12-14

    ISS014-E-09897 (14 Dec. 2006) -- European Space Agency (ESA) astronaut Thomas Reiter, STS-116 mission specialist, works with the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station during in-flight maintenance (IFM) while Space Shuttle Discovery was docked with the station.

  18. Preventive Maintenance Process

    NASA Technical Reports Server (NTRS)

    Ciaruffoli, Veronica; Bramley, Craig; Matteson, Mike

    2001-01-01

    The Preventive Maintenance (PM) program at Stennis Space Center (SSC) evolved from an ineffective and poorly organized state to a highly organized state in which it became capable of tracking equipment, planning jobs with man hour estimates, and supporting outsourcing. This viewgraph presentation traces the steps the program took to improve itself.

  19. 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.

  20. Kinetics of epidermal growth factor in saliva.

    PubMed

    Ino, M; Ushiro, K; Ino, C; Yamashita, T; Kumazawa, T

    1993-01-01

    Human epidermal growth factor (hEGF) stimulates the growth and differentiation of various tissues. We measured EGF levels in saliva (n = 128), urine (n = 94), and serum (n = 99) with radioimmunoassay in order to study the kinetics of hEGF in saliva of normal subjects and patients with oral disease. Salivary EGF levels showed an apparent diurnal rhythm related to the taking of meals. Urinary and serum EGF levels showed no obvious diurnal rhythm. There was no significant correlation between salivary and urinary EGF levels, nor between salivary and serum EGF levels. Salivary EGF levels were significantly lower in the younger group (0-9 years old, 3.06 +/- 0.32 ng/ml, p < 0.05) than in the elder group (10-79 years old, 4.78 +/- 3.5 ng/ml), but did not correlate with age in the elder group. There was no significant difference between males and females between EGF levels in saliva, urine or serum. The relative proportion of EGF levels in submandibular gland saliva, parotid saliva, and whole saliva was 1:6:4. The positive rate of immunohistochemical EGF showed no significant differences between submandibular gland, parotid gland, sublingual gland or minor salivary gland. Salivary EGF levels were markedly low in patients with oral inflammations (stomatitis aphthosa, or peritonsillar abscess) or head and neck tumors (squamous cell carcinoma of the tongue, oral cavity, hypopharynx or larynx). These findings may be significant pathophysiologically. Low salivary EGF levels may reduce the capacity of oral mucosal defense mechanisms to fight against injury by physiochemical agents.

  1. The management of toxic epidermal necrolysis.

    PubMed

    Fernando, Suran L

    2012-08-01

    The mortality rate of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is high; approximately 5% for SJS and 25% for TEN. It is therefore vital for the treating physician to recognise SJS and TEN promptly through the identification of these diseases' characteristic clinical features so that the offending drug is promptly withdrawn, supportive therapy is administered and adjunctive therapies are considered. Supportive therapy addressing the manifestations and complications of acute skin failure include monitoring the fluid - electrolyte balance and providing enteral or parenteral nutrition, wound care and treatment of sepsis. In addition, supportive care of the affected mucosal surfaces is required through the use of aggressive ocular lubrication, topical corticosteroids, hygienic mouthwashes and oral anaesthetics, together with monitoring for urinary retention. There is sufficient evidence for the use of intravenous immune globulin in the acute management of SJS/TEN provided an adequate dose of 2-3 g/kg is administered. Cyclosporine appears to also be an effective agent although randomised control studies are required to demonstrate its benefit and establish the dose, duration of therapy and safety profile. The role of corticosteroids is currently under revision. Some earlier studies have shown a lack of efficacy or increased mortality in their use but the use of high doses early in the course of disease may actually reduce morbidity and mortality. The role of plasmapheresis, anti-tumour necrosis factor (TNF) biologics and N-acetylcysteine is promising but further studies are required to elucidate their benefit. Preventative strategies such as pharmacogenetic screening needs to be strongly considered, with the provision of cost-effective assays with a rapid turn-around time.

  2. Toxic epidermal necrolysis associated with rifaximin.

    PubMed

    Patel, Aneesh S; Supan, Elisa M; Ali, Shereef N

    2013-05-15

    The case of a patient who developed toxic epidermal necrolysis (TEN) after treatment with rifaximin for hepatic encephalopathy is reported. A 62-year-old Caucasian woman with a history of alcohol abuse arrived at the emergency room with complaints of abdominal pain and acute onset of jaundice, likely secondary to alcoholic hepatitis. Laboratory tests and multiple imaging studies conducted in the emergency department revealed signs of chronic liver disease and common bile duct dilation with ascites. At admission, she had low concentrations of serum sodium, serum chloride, serum creatinine, and serum albumin and elevated liver function test values. On hospital day 7, the patient developed an altered mental status, which was diagnosed as toxic metabolic encephalopathy, primarily hepatic in origin. The patient was given lactulose 20 g via nasogastric tube every 12 hours and rifaximin 400 mg orally every 8 hours. The patient received only two doses of the rifaximin before it was discontinued. On hospital day 27, oral rifaximin 550 mg twice daily was initiated. After 12 days of rifaximin therapy, the patient developed a diffuse, erythematous, maculopapular, and desquamating cutaneous reaction on her chest, arms, and legs. The suspected diagnosis was determined to be a severe cutaneous adverse drug reaction, possibly TEN. Use of the Naranjo et al. scale revealed that rifaximin was a possible cause of the reaction. Rifaximin was discontinued, and antihistamines and i.v. corticosteroids were initiated. The reaction completely resolved after one week. A 62-year-old woman developed possible TEN after receiving rifaximin to treat hepatic encephalopathy.

  3. Melanocyte-specific CD8+ T cells are associated with epidermal depigmentation in a novel mouse model of vitiligo.

    PubMed

    You, S; Cho, Y-H; Byun, J-S; Shin, E-C

    2013-10-01

    In the present study, we established a novel murine model of vitiligo by sequential prime/boost immunizations into the hind footpad and tail dermis with tyrosinase-related protein 2 (TRP2)-180 (SVYDFFVWL) peptide, lipopolysaccharides and cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides. Immunized mice developed epidermal depigmentation in the tail skin without hair depigmentation, thereby differentiating this approach from established models of vitiligo. Following intradermal tail immunization, activated CD8(+) interferon (IFN)-γ(+) T cells were recruited locally to the tail skin. In-vivo cytotoxicity assays demonstrated specific lysis of TRP2-180-presenting cells in immunized mice. Furthermore, the extent of skin depigmentation correlated with the frequency of TRP2-180-specific splenic CD8(+) T cells, as determined by IFN-γ and tumour necrosis factor (TNF)-α production, and cytotoxic degranulation evidenced by CD107a staining. These findings suggest a correlation between the presence of TRP2-180-specific CD8(+) effector T cells and the development of depigmented skin lesions in our vitiligo model. This new model of vitiligo, characterized by skin depigmentation without hair depigmentation, is more similar to human disease than previous murine models. Therefore, this model is well suited to future studies on the pathogenesis of vitiligo and the development of novel therapeutics for vitiligo.

  4. 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

  5. Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies

    PubMed Central

    Diaz Miqueli, A; Rolff, J; Lemm, M; Fichtner, I; Perez, R; Montero, E

    2009-01-01

    As epidermal growth factor receptor (EGFR) has been reported to be a radiation response modulator, HER inhibitors are regarded to act as potential radiosensitisers. Our study examined the role of nimotuzumab and cetuximab both, the two monoclonal antibodies (mAbs) to EGFR, as radiosensitisers in a murine glioma model in vivo. Co-administration of both the antibodies with radiation increased the radiosensitivity of U87MG, resulting in a significant delay of subcutaneous (s.c.) tumour growth. Furthermore, the addition of antibodies to the radiation decreased brain tumour sizes and is inhibited by 40–80% the increased tumour cell invasion provoked by radiotherapy, although promoted tumour cell apoptosis. Whereas nimotuzumab led to a reduction in the size of tumour blood vessels and proliferating cells in s.c. tumours, cetuximab had no significant antiangiogenic nor antiproliferative activity. In contrast, cetuximab induced a more marked inhibition of EGFR downstream signalling compared with nimotuzumab. Moreover, both antibodies reduced the total number of radioresistant CD133+ cancer stem cells (CSCs). These results were encouraging, and showed the superiority of combined treatment of mAbs to EGFR and radiation over each single therapy against glioblastoma multiforme (GBM), confirming the role of these drugs as radiosensitisers in human GBM. In addition, we first showed the ability of mAb specifics against EGFR to target radioresistant glioma CSC, supporting the potential use in patients. PMID:19293809

  6. 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.

  7. Prolactin decreases epidermal growth factor receptor kinase activity via a phosphorylation-dependent mechanism.

    PubMed

    Quijano, V J; Sheffield, L G

    1998-01-09

    Previously, we have shown that prolactin inhibits epidermal growth factor (EGF)-induced mitogenesis in mouse mammary epithelial cells without altering the response to other growth promoting agents. This effect has been associated with reduced EGF-induced EGF receptor (EGFR) tyrosine phosphorylation, Grb-2 association, and Ras activation. Our current hypothesis is that prolactin induces an alteration in EGFR kinase activity via a phosphorylation-dependent mechanism. To test this hypothesis, we treated normal murine mammary gland cells with or without 100 ng/ml prolactin. EGFR isolated by wheat germ agglutinin affinity chromatography from nontreated cells exhibited substantial ligand-induced phosphorylation, and EGFR isolated from prolactin-treated cells displayed minimal EGF-induced EGFR phosphorylation, as well as decreased kinase activity toward exogenous substrates. The observed decrease in ligand-induced EGFR phosphorylation could not be attributed to either differential amounts of EGFR, decreased EGF binding affinity, or the presence of a phosphotyrosine phosphatase or ATPase. EGFR isolated from prolactin-treated cells exhibited increased phosphorylation on threonine. Removal of this phosphorylation with alkaline phosphatase restored EGFR kinase activity to levels observed in nontreated cells. Therefore, these results suggest that prolactin antagonizes EGF signaling by increasing EGFR threonine phosphorylation and decreasing EGF-induced EGFR tyrosine phosphorylation.

  8. A dominant negative mutation suppresses the function of normal epidermal growth factor receptors by heterodimerization.

    PubMed Central

    Kashles, O; Yarden, Y; Fischer, R; Ullrich, A; Schlessinger, J

    1991-01-01

    Recent studies provide evidence that defective receptors can function as a dominant negative mutation suppressing the action of wild-type receptors. This causes various diminished responses in cell culture and developmental disorders in murine embryogenesis. Here, we describe a model system and a potential mechanism underlying the dominant suppressing response caused by defective epidermal growth factor (EGF) receptors. We used cultured 3T3 cells coexpressing human wild-type receptors and an inactive deletion mutant lacking most of the cytoplasmic domain. When expressed alone, EGF was able to stimulate the dimerization of either wild-type or mutant receptors in living cells as revealed by chemical covalent cross-linking experiments. In response to EGF, heterodimers and homodimers of wild-type and mutant receptors were observed in cells coexpressing both receptor species. However, only homodimers of wild-type EGF receptors underwent EGF-induced tyrosine autophosphorylation in living cells. These results indicate that the integrity of both receptor moieties within receptor dimers is essential for kinase activation and autophosphorylation. Moreover, the presence of mutant receptors in cells expressing wild-type receptors diminished the number of high-affinity binding sites for EGF, reduced the rate of receptor endocytosis and degradation, and diminished biological signalling via EGF receptors. We propose that heterodimerization with defective EGF receptors functions as a dominant negative mutation suppressing the activation and response of normal receptors by formation of unproductive heterodimers. Images PMID:1705006

  9. Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review.

    PubMed

    Gerull, Roland; Nelle, Mathias; Schaible, Thomas

    2011-06-01

    The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome. PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases. Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. Stevens-Johnson syndrome affects <10%, whereas involvement of 10%-30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%-50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be

  10. Activation of epidermal toll-like receptor 2 enhances tight junction function – Implications for atopic dermatitis and skin barrier repair

    PubMed Central

    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.

    2012-01-01

    Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus (S. aureus) skin infections. S. aureus is sensed by many pattern recognition receptors including toll-like receptor (TLR) 2. 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, CLDN1, CLDN23, occludin and 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 to nonatopic (NA) 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 play a role in their incompetent skin barrier. PMID:23223142

  11. Plaque assay for murine norovirus.

    PubMed

    Gonzalez-Hernandez, Mariam B; Bragazzi Cunha, Juliana; Wobus, Christiane E

    2012-08-22

    Murine norovirus (MNV) is the only member of the Norovirus genus that efficiently grows in tissue culture. Cell lysis and cytopathic effect (CPE) are observed during MNV-1 infection of murine dendritic cells or macrophages. This property of MNV-1 can be used to quantify the number of infectious particles in a given sample by performing a plaque assay. The plaque assay relies on the ability of MNV-1 to lyse cells and to form holes in a confluent cell monolayer, which are called plaques. Multiple techniques can be used to detect viral infections in tissue culture, harvested tissue, clinical, and environmental samples, but not all measure the number of infectious particles (e.g. qRT-PCR). One way to quantify infectious viral particles is to perform a plaque assay, which will be described in detail below. A variation on the MNV plaque assay is the fluorescent focus assay, where MNV antigen is immunostained in cell monolayers. This assay can be faster, since viral antigen expression precedes plaque formation. It is also useful for titrating viruses unable to form plaques. However, the fluorescent focus assay requires additional resources beyond those of the plaque assay, such as antibodies and a microscope to count focus-forming units. Infectious MNV can also be quantified by determining the 50% Tissue Culture Infective Dose (TCID50). This assay measures the amount of virus required to produce CPE in 50% of inoculated tissue culture cells by endpoint titration. However, its limit of detection is higher compared to a plaque assay. In this article, we describe a plaque assay protocol that can be used to effectively determine the number of infectious MNV particles present in biological or environmental samples. This method is based on the preparation of 10-fold serial dilutions of MNV-containing samples, which are used to inoculate a monolayer of permissive cells (RAW 264.7 murine macrophage cells). Virus is allowed to attach to the cell monolayer for a given period of

  12. Limited Role of Murine ATM in Oncogene-Induced Senescence and p53-Dependent Tumor Suppression

    PubMed Central

    Martinez-Pastor, Barbara; Ortega-Molina, Ana; Soria, Rebeca; Collado, Manuel; Fernandez-Capetillo, Oscar; Serrano, Manuel

    2009-01-01

    Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability. PMID:19421407

  13. Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

    PubMed Central

    GUZMÁN-URIBE, Daniela; ALVARADO-ESTRADA, Keila Neri; PIERDANT-PÉREZ, Mauricio; TORRES-ÁLVAREZ, Bertha; SÁNCHEZ-AGUILAR, Jesus Martin; ROSALES-IBÁÑEZ, Raúl

    2017-01-01

    Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%), meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues. PMID:28403359

  14. Immune sensitization against epidermal antigens in polymorphous light eruption

    SciTech Connect

    Gonzalez-Amaro, R.; Baranda, L.; Salazar-Gonzalez, J.F.; Abud-Mendoza, C.; Moncada, B. )

    1991-01-01

    To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.

  15. Clinical and Economic Benefits of Autologous Epidermal Grafting

    PubMed Central

    Kirsner, Robert S

    2016-01-01

    Chronic wounds are an increasingly prevalent disease with a significant healthcare burden. These wounds often do not respond to standard of care therapy alone, requiring the use of adjuvant therapies. Epidermal grafting, previously utilized primarily for correction of leukoderma, is increasingly being recognized as a beneficial therapy for wounds, both acute and chronic. Epidermal grafting has been shown to be effective in the management of chronic wounds, with successful healing in refractory patients. It has not only been shown to be effective, but it is also associated with lower cost and morbidity than traditional skin grafting techniques as well as improved donor site healing. Through the use of a novel epidermal harvesting system, the CelluTome™ Epidermal Harvesting System (KCI, an Acelity company, San Antonio, TX), this treatment modality has become more standardized, reproducible, and easy to use as well as less time consuming, making its use in the clinical setting more convenient and beneficial. Epidermal grafting, therefore, represents a promising, efficacious, and cost-effective option for treatment of refractory non-healing wounds. PMID:27994993

  16. ATML1 promotes epidermal cell differentiation in Arabidopsis shoots.

    PubMed

    Takada, Shinobu; Takada, Nozomi; Yoshida, Ayaka

    2013-05-01

    Molecular mechanisms that generate distinct tissue layers in plant shoots are not well understood. ATML1, an Arabidopsis homeobox gene, is expressed in the outermost cell layer, beginning at an early stage of development. The promoters of many epidermis-specific genes, including ATML1, contain an ATML1-binding site called an L1 box, suggesting that ATML1 regulates epidermal cell fate. Here, we show that overexpression of ATML1 was sufficient to activate the expression of epidermal genes and to induce epidermis-related traits such as the formation of stomatal guard cells and trichome-like cells in non-epidermal seedling tissues. Detailed observation of the division planes of these ectopic stomatal cells suggested that a near-surface position, as well as epidermal cell identity, were required for regular anticlinal cell division, as seen in wild-type epidermis. Moreover, analyses of a loss-of-function mutant and overexpressors implied that differentiation of epidermal cells was associated with repression of mesophyll cell fate. Collectively, our studies contribute new information about the molecular basis of cell fate determination in different layers of plant aerial organs.

  17. 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. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  18. Human epidermal plasminogen activator. Characterization, localization, and modulation.

    PubMed

    Morioka, S; Jensen, P J; Lazarus, G S

    1985-12-01

    Using biochemical and immunocytochemical approaches, we have investigated the plasminogen activator (PA) of primary human epidermal cell cultures. A rabbit antibody raised against human urinary PA (urokinase) inhibited greater than or equal to 96% of the PA activity in the keratinocyte cultures. Immunoblot and double immunodiffusion analyses of keratinocyte PA with anti-urokinase antibody confirmed that epidermal PA was of the urokinase type. Immunocytochemical investigation of human keratinocyte cultures with anti-urokinase antibody revealed two characteristic staining patterns for PA. First, cells at the advancing edge of subconfluent colonies were cytoplasmically stained in a granular pattern. Similar staining was observed at the migrating edges of confluent epidermal cell cultures that had been wounded by cutting with a blade. This induction of PA staining was independent of cell division. Secondly, differentiated epidermal cells located on the surface of colonies were stained either at the plasma membrane or homogeneously throughout the cell. The highly differentiated, spontaneously shed cells were usually very heavily stained by anti-urokinase antibody. These immunocytochemical experiments suggest that PA expression is highly regulated in human epidermal cells. Specifically, PA expression appears to be related to cellular differentiation and to cell movement in expanding or wounded keratinocyte colonies.

  19. Trafficking through COPII Stabilises Cell Polarity and Drives Secretion during Drosophila Epidermal Differentiation

    PubMed Central

    Norum, Michaela; Tång, Erika; Chavoshi, Tina; Schwarz, Heinz; Linke, Dirk; Uv, Anne; Moussian, Bernard

    2010-01-01

    Background The differentiation of an extracellular matrix (ECM) at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation. Principal Findings We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus. Conclusion Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes. PMID:20520821

  20. Tacrolimus prevents murine cerebral malaria.

    PubMed

    Bao, Lam Quoc; Nhi, Dang My; Huy, Nguyen Tien; Hamano, Shinjiro; Hirayama, Kenji

    2017-02-01

    Tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. Tacrolimus is also reported to inhibit Plasmodium falciparum growth in vitro. Here, we report that tacrolimus prevented the death from cerebral malaria of Plasmodium berghei ANKA-infected C57BL/6J mice, but not their death from malaria due to the high parasitaemia and severe anaemia. The mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malaria earlier than tacrolimus-treated littermates. Tacrolimus attenuated the infiltration of mononuclear cells including pathogenic CD8(+) T cells into the brain. It appears to prevent murine cerebral malaria through the inhibition of cerebral infiltration of CD8(+) T cells. © 2016 John Wiley & Sons Ltd.

  1. Murine models of ulcerative colitis.

    PubMed

    Flynn, Christopher; Levine, Joel; Rosenberg, Daniel W

    2003-06-01

    Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology limited to the large intestine. The disease is prevalent in industrial societies and is associated with specific ethnic populations. A number of murine models, each focused on distinct aspects of the disease process, were developed over the past 20 years to further our understanding of the pathogenesis of UC. These models have been and remain our best resource for the study of the disorder as a result of their homology to human UC and the ease in which they can be manipulated and examined. This review examines and distills what has been leamed from these models and how this information is related back to human UC.

  2. Murine model of TB meningitis.

    PubMed

    Gupta, Umesh Datta; Abbas, Ali; Kashyap, Raj Pal Singh; Gupta, Pushpa

    2016-12-01

    Central nervous system (CNS) infections caused by Mycobacterium tuberculosis (MTB) are the most severe forms of extrapulmonary TB (EPTB) due to high levels of mortality and neurological morbidity. Limited studies are available on CNS-TB animal-model development, despite the steady rise in cerebral-TB cases in India over the past decade. This study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients. Groups of mice were infected intravenously with an MTB C3 strain isolated from the CSF of CNS-TB patients in order to mimic the dynamics of actual infection. Brain and lung tissue were evaluated for bacterial burden, as well as histopathology and surrogate markers of TB infection at 30- and 50-days post-infection. Mice infected intravenously with MTB C3 strains showed progressive development of CNS disease, with high bacillary burden in the lungs during the initial stage (30days), which eventually disseminated to the brain at a later stage (50days). All C3-infected mice showed elevated levels of mycobacterial antigens and antibodies, as well as increased T cell adenosine deaminase activity in brain homogenates, which explicitly correlated with mycobacterial load in the brain and chronic brain pathology. High mortality rates (60%) were associated with mice infected with the C3 strain as compared to those of controls. Our findings demonstrated the design of a novel murine model of CNS-TB using a C3 strain and that replicated events of EPTB dissemination. This model will promote efforts to understand the pathogenesis CNS-TB infection for development of improved therapeutic interventions in the future. Copyright © 2016.

  3. CFB refractory maintenance

    SciTech Connect

    Johnson, R.C.

    1994-12-31

    The CFB maintenance manager has to make rapid-fire decisions regarding refractory maintenance during short or unscheduled turnarounds. This presentation offers a hands-on approach to expedient refractory failure analyses with specific repair recommendations. Photographs of most typical CFB refractory failures and their structural repairs are discussed. The most reliable repairs can be expected by using the latest state-of-the-art refractory materials and installation techniques. Refractory materials are consumable; therefore minor repairs should always be conducted at the first opportunity; this will preclude future major repairs. During a short or unscheduled outage, major repairs should be confined to the specific structural repair site; the removal of good, serviceable refractory is unnecessary under these conditions.

  4. 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.

  5. Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors.

    PubMed

    Taniguchi, Hirokazu; Takeuchi, Shinji; Fukuda, Koji; Nakagawa, Takayuki; Arai, Sachiko; Nanjo, Shigeki; Yamada, Tadaaki; Yamaguchi, Hiroyuki; Mukae, Hiroshi; Yano, Seiji

    2017-01-01

    Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement. The resistant cells did not have the secondary ALK mutations frequently occurring in crizotinib-resistant cells, and these cells were cross-resistant to alectinib and ceritinib as well. In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model. Cell clone #2 did not have an EGFR mutation, but the expression of amphiregulin (AREG), one of EGFR ligands, was significantly increased. A knockdown of AREG with small interfering RNAs restored the sensitivity to crizotinib. These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.

  6. 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.

  7. 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.

  8. 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…

  9. 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…

  10. Management Aspects of Software Maintenance.

    DTIC Science & Technology

    1984-09-01

    TRADITIONAl METHODS ..... ............. 50 C. PARAMETRIC MODELS ..... .............. 53 D. ESTIMATING MAINTENANCE COSTS ... ......... 57 1. Planning...maintenance. 10 10A 4 7he extensive research dcne cn software development and on the management of the development process is only ncw begin- ning to...and external factors. C. GENEEAL PROCEDURE The procedure used was to research literature concerning software maintenance. Particular emphasis was

  11. 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…

  12. Effects of moisturization on epidermal homeostasis and differentiation.

    PubMed

    Short, R W; Chan, J L; Choi, J M; Egbert, B M; Rehmus, W E; Kimball, A B

    2007-01-01

    Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine.

  13. Epidermal nevus syndrome with hypermelanosis and chronic hyponatremia.

    PubMed

    Yu, T W; Tsau, Y K; Young, C; Chiu, H C; Shen, Y Z

    2000-02-01

    Epidermal nevus syndrome is seldom encountered, and its association with hypermelanosis and the chronic syndrome of inappropriate antidiuretic hormone secretion (SIADH) has never been reported. A male neonate who developed intractable seizures and hyponatremia soon after birth is reported. He had alopecic patches on the scalp at birth. Large areas of skin hyperpigmentation, and epidermal nevi developed gradually. The clinical picture of hypotonic hyponatremia, high urine osmolality, elevated urine sodium, and euvolemia was compatible with SIADH. The seizures did not correlate with the hyponatremia, and no other cause for the seizures could be identified. The hyponatremia became chronic and was treated with a direct supply of sodium chloride. The development of the patient was markedly delayed at the last visit when he was 1 year of age. It is suggested that hypermelanosis and chronic SIADH may also be a variant presentation of epidermal nevus syndrome.

  14. 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

  15. 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.

  16. Autologous Epidermal Grafting Using a Novel Negative Pressure Epidermal Harvesting System in a Case of Stable Vitiligo

    PubMed Central

    Thirunavukkarasu, Vanathi; Navaneetha Krishnan, Paru Priyadarshini; Danasekaran, Nithya Gayathri Devi; Rajendrabose, Ratnavel

    2016-01-01

    Vitiligo is a common pigmentary disorder of the skin with a great amount of social stigma attached to it. Though various medical modalities are available for the treatment of stable vitiligo, surgical modality remains the treatment of choice for stable and localized vitiligo. The surgical options range from simple punch grafting to the recent epidermal harvesting methods using a negative pressure unit. Although successful use of multiple methods of epidermal grafting has been reported, most of them are cumbersome and time-consuming. The new automated epidermal harvesting system now commercially available involves a tool that applies both heat and suction concurrently to normal skin to induce epidermal micrografts. Hence it serves as a safe, quick and cost-effective method without anesthesia, with a very minimal downtime for healing and requires an optimal expertise. The duration of repigmentation seems to be faster and more uniform compared to other procedures. We would like to share our experience with the negative pressure epidermal harvesting method in a patient with stable vitiligo. PMID:28003945

  17. Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects.

    PubMed

    Guzmán-Uribe, Daniela; Alvarado-Estrada, Keila Neri; Pierdant-Pérez, Mauricio; Torres-Álvarez, Bertha; Sánchez-Aguilar, Jesus Martin; Rosales-Ibáñez, Raúl

    2017-01-01

    The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

  18. [Toxic epidermal necrolysis and development of liver abscesses].

    PubMed

    Domínguez-Borgúa, Andrés; González, Itzel; Morales, Lucero; Martínez-Carrillo, Francisco Manuel; Palacios, Paul

    2015-01-01

    Pharmacologic hypersensitivities commonly express cutaneous manifestations, and the highest mortality is found in Stevens Johnson's syndrome and toxic epidermal necrolysis, mostly associated with antibiotics and anticonvulsive drugs. Toxic epidermal necrolysis is related in 80% of cases to pharmacologic hypersensitivity and systemic consequences may be found; hepatic injury has been described, but the finding of liver abscesses has not been reported among common injuries. The case of a patient with a rapid development of multiple liver abscesses in the clinical setting of hypersensitivity due to lamotrigine and the discussion of probable etiologies and management is presented.

  19. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases.

    PubMed

    Kubo, Akiharu; Nagao, Keisuke; Amagai, Masayuki

    2012-02-01

    Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases.

  20. The human analog of murine cystein rich protein 61 [correction of 16] is a 1alpha,25-dihydroxyvitamin D3 responsive immediate early gene in human fetal osteoblasts: regulation by cytokines, growth factors, and serum.

    PubMed

    Schütze, N; Lechner, A; Groll, C; Siggelkow, H; Hüfner, M; Köhrle, J; Jakob, F

    1998-04-01

    1Alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is a potent mediator of differentiation and maintenance of specific functions of osteoblasts. To detect novel targets for 1,25-(OH)2D3 action, we applied differential display PCR to human fetal osteoblast-like cells and identified the human analog of murine cystein rich protein 61 (hCYR61) as a 1,25-(OH)2D3-responsive immediate early gene in differentiated fetal osteoblast-like cells. The murine gene CYR61 is important for cell-cell and cell-matrix interactions, and it belongs to an emerging gene family of cysteine-rich proteins. hCYR61 messenger RNA (mRNA) steady-state levels were stimulated 11-fold by 10 nM 1,25-(OH)2D3 by 1 h and declined to control levels by 4 h. This transient stimulation of hCYR61 mRNA was not inhibited by cycloheximide but was prevented by actinomycin D, indicating that the 1,25-(OH)2D3 effect involves transcriptional events and does not require de novo protein synthesis. hCYR61 mRNA stability was not influenced by 1,25(OH)2D3, whereas cycloheximide treatment stabilized hCYR61 mRNA. FCS, as well as growth factors and cytokines such as basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor alpha, and interleukin-1, strongly elevated hCYR61 mRNA steady-state levels within 1 h. hCYR61 mRNA was expressed also in primary human osteoblasts and osteosarcoma cell lines. Using a commercial tissue blot, hCYR61 mRNA was only observed in skeletal muscle. The fast and transient response of hCYR 61 to 1,25-(OH)2D3, serum, growth factors, and cytokines suggests an important role of hCYR61 for osteoblast function and differentiation.

  1. 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.

  2. Capecitabine maintenance therapy following docetaxel/capecitabine combination treatment in patients with metastatic breast cancer.

    PubMed

    Surmeli, Zeki Gokhan; Varol, Umut; Cakar, Burcu; Degirmenci, Mustafa; Arslan, Cagatay; Piskin, Gonul Demir; Zengel, Baha; Karaca, Burcak; Sanli, Ulus Ali; Uslu, Ruchan

    2015-10-01

    The present study aimed to analyze the efficacy of maintenance therapy with single agent capecitabine for human epidermal growth factor receptor (HER2) negative metastatic breast cancer (MBC) patients following disease control with 6 cycles of docetaxel plus capecitabine chemotherapy as the first-line treatment. As an initial treatment, 6 cycles of docetaxel plus capecitabine followed by maintenance therapy with capecitabine were administered. A total of 55 patients received combination therapy and 48 patients proceeded to maintenance therapy: Of these, 32 patients (66.7%) were postmenopausal and 37 (77.1%) had estrogen and progesterone receptor positive disease. The median progression-free survival rate with maintenance therapy was 5.5 months (95% CI, 0-11.4 months) and the median overall survival (OS) was 26.6 months (95% CI, 21.8-30.1 months). The use of maintenance therapy improved previous responses in 4 patients (8.3%; 2 partial and 2 complete responses) and 32 patients (66.7%) had stable disease. The median number of maintenance therapy cycles applied was 6.5 (range 1-28, total 441). The observation of side effects, including grade 3/4 neutropenia, febrile neutropenia and fatigue was more common during combination therapy. The results of the present study indicate that maintenance with single agent capecitabine therapy is an effective and tolerable treatment option for HER2 negative MBC patients in which disease control with 6 cycles of docetaxel plus capecitabine chemotherapy is achieved in the first-line setting.

  3. The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte differentiation.

    PubMed

    Akiyama, Masashi

    2014-03-01

    ATP-binding cassette (ABC) transporters form a large superfamily of transporters that bind and hydrolyze ATP to transport various molecules across limiting membranes or into vesicles. The ABCA subfamily members are thought to transport lipid materials. ABCA12 is a keratinocyte transmembrane lipid transporter protein associated with the transport of lipids via lamellar granules. ABCA12 is considered to transport lipids including ceramides to form extracellular lipid layers in the stratum corneum of the epidermis, which is essential for skin barrier function. ABCA12 mutations are known to underlie the three major types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma. ABCA12 mutations result in defective lipid transport via lamellar granules in the keratinocytes, leading to ichthyosis phenotypes from malformation of the stratum corneum lipid barrier. Studies on ABCA12-deficient bioengineered models have revealed that lipid transport by ABCA12 is required for keratinocyte differentiation and epidermal morphogenesis. Defective lipid transport due to loss of ABCA12 function leads to the accumulation of intracellular lipids, including glucosylceramides and gangliosides, in the epidermal keratinocytes. The accumulation of gangliosides seems to result in the apoptosis of Abca12(-/-) keratinocytes. It was reported that AKT activation occurs in Abca12(-/-) granular-layer keratinocytes, which suggests that AKT activation serves to prevent the cell death of Abca12(-/-) keratinocytes. 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. © 2013.

  4. 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

  5. Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection.

    PubMed

    Gómez-Rial, J; Curras-Tuala, M J; Talavero-González, C; Rodríguez-Tenreiro, C; Vilanova-Trillo, L; Gómez-Carballa, A; Rivero-Calle, I; Justicia-Grande, A; Pardo-Seco, J; Redondo-Collazo, L; Salas, A; Martinón-Torres, F

    2017-05-30

    The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r(2) = -0.63). The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.

  6. 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.

  7. Qualitative Maintenance Experience Handbook

    DTIC Science & Technology

    1975-10-20

    rdme hinge nonression springn. 7. Rem~ove 3 nuts, 1w- ashers , and bolts holding hinge pin halvers together. 8. Remove piD pin senuring iury strut and...bolt, nut. i,, asher , and pin. ONSTALLATTON: I. Reverse )’F -emov,,I. P. Aotuator is pr c-ad;Iusted to lenth and probably does not need adjust 3. TI...time in that syst-m and also permits malfunctions to be induces in a system not directly associated with the maintenance. [ ITI I - ___ ~ JaI , FLIGHT

  8. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  9. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  10. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance with...

  11. Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle.

    PubMed

    El-Hayek, Stephany; Demeestere, Isabelle; Clarke, Hugh J

    2014-11-25

    Fertility depends on the precise coordination of multiple events within the ovarian follicle to ensure ovulation of a fertilizable egg. FSH promotes late follicular development, including expression of luteinizing hormone (LH) receptor by the granulosa cells. Expression of its receptor permits the subsequent LH surge to trigger the release of ligands that activate EGF receptors (EGFR) on the granulosa, thereby initiating the ovulatory events. Here we identify a previously unknown role for FSH in this signaling cascade. We show that follicles of Fshb(-/-) mice, which cannot produce FSH, have a severely impaired ability to support two essential EGFR-regulated events: expansion of the cumulus granulosa cell layer that encloses the oocyte and meiotic maturation of the oocyte. These defects are not caused by an inability of Fshb(-/-) oocytes to produce essential oocyte-secreted factors or of Fshb(-/-) cumulus cells to respond. In contrast, although expression of both Egfr and EGFR increases during late folliculogenesis in Fshb(+/-) females, these increases fail to occur in Fshb(-/-) females. Remarkably, supplying a single dose of exogenous FSH activity to Fshb(-/-) females is sufficient to increase Egfr and EGFR expression and to restore EGFR-dependent cumulus expansion and oocyte maturation. These studies show that FSH induces an increase in EGFR expression during late folliculogenesis and provide evidence that the FSH-dependent increase is necessary for EGFR physiological function. Our results demonstrate an unanticipated role for FSH in establishing the signaling axis that coordinates ovulatory events and may contribute to the diagnosis and treatment of some types of human infertility.

  12. Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle

    PubMed Central

    El-Hayek, Stephany; Demeestere, Isabelle; Clarke, Hugh J.

    2014-01-01

    Fertility depends on the precise coordination of multiple events within the ovarian follicle to ensure ovulation of a fertilizable egg. FSH promotes late follicular development, including expression of luteinizing hormone (LH) receptor by the granulosa cells. Expression of its receptor permits the subsequent LH surge to trigger the release of ligands that activate EGF receptors (EGFR) on the granulosa, thereby initiating the ovulatory events. Here we identify a previously unknown role for FSH in this signaling cascade. We show that follicles of Fshb−/− mice, which cannot produce FSH, have a severely impaired ability to support two essential EGFR-regulated events: expansion of the cumulus granulosa cell layer that encloses the oocyte and meiotic maturation of the oocyte. These defects are not caused by an inability of Fshb−/− oocytes to produce essential oocyte-secreted factors or of Fshb−/− cumulus cells to respond. In contrast, although expression of both Egfr and EGFR increases during late folliculogenesis in Fshb+/− females, these increases fail to occur in Fshb−/− females. Remarkably, supplying a single dose of exogenous FSH activity to Fshb−/− females is sufficient to increase Egfr and EGFR expression and to restore EGFR-dependent cumulus expansion and oocyte maturation. These studies show that FSH induces an increase in EGFR expression during late folliculogenesis and provide evidence that the FSH-dependent increase is necessary for EGFR physiological function. Our results demonstrate an unanticipated role for FSH in establishing the signaling axis that coordinates ovulatory events and may contribute to the diagnosis and treatment of some types of human infertility. PMID:25385589

  13. Follistatin attenuates radiation-induced fibrosis in a murine model

    PubMed Central

    Forrester, Helen B.; de Kretser, David M.; Leong, Trevor; Hagekyriakou, Jim; Sprung, Carl N.

    2017-01-01

    Purpose Fibrosis can be a disabling, severe side effect of radiotherapy that can occur in patients, and for which there is currently no effective treatment. The activins, proteins which are members of the TGFβ superfamily, have a major role in stimulating the inflammatory response and subsequent fibrosis. Follistatin is an endogenous protein that binds the activins virtually irreversibly and inhibits their actions. These studies test if follistatin can attenuate the fibrotic response using a murine model of radiation-induced fibrosis. Experimental design C57BL/6 mice were subcutaneously injected with follistatin 24 hours prior to irradiation. Mice were irradiated in a 10 x 10 mm square area of the right hind leg with 35 Gy and were given follistatin 24 hours before radiation and three times a week for six months following. Leg extension was measured, and tissue was collected for histological and molecular analysis to evaluate the progression of the radiation-induced fibrosis. Results Leg extension was improved in follistatin treated mice compared to vehicle treated mice at six months after irradiation. Also, epidermal thickness and cell nucleus area of keratinocytes were decreased by the follistatin treatment compared to the cells in irradiated skin of control mice. Finally, the gene expression of transforming growth factor β1 (Tgfb1), and smooth muscle actin (Acta2) were decreased in the irradiated skin and Acta2 and inhibin βA subunit (Inhba) were decreased in the irradiated muscle of the follistatin treated mice. Conclusions Follistatin attenuated the radiation-induced fibrotic response in irradiated mice. These studies provide the data to support further investigation of the use of follistatin to reduce radiation-induced fibrosis in patients undergoing radiotherapy for cancer. PMID:28301516

  14. Follistatin attenuates radiation-induced fibrosis in a murine model.

    PubMed

    Forrester, Helen B; de Kretser, David M; Leong, Trevor; Hagekyriakou, Jim; Sprung, Carl N

    2017-01-01

    Fibrosis can be a disabling, severe side effect of radiotherapy that can occur in patients, and for which there is currently no effective treatment. The activins, proteins which are members of the TGFβ superfamily, have a major role in stimulating the inflammatory response and subsequent fibrosis. Follistatin is an endogenous protein that binds the activins virtually irreversibly and inhibits their actions. These studies test if follistatin can attenuate the fibrotic response using a murine model of radiation-induced fibrosis. C57BL/6 mice were subcutaneously injected with follistatin 24 hours prior to irradiation. Mice were irradiated in a 10 x 10 mm square area of the right hind leg with 35 Gy and were given follistatin 24 hours before radiation and three times a week for six months following. Leg extension was measured, and tissue was collected for histological and molecular analysis to evaluate the progression of the radiation-induced fibrosis. Leg extension was improved in follistatin treated mice compared to vehicle treated mice at six months after irradiation. Also, epidermal thickness and cell nucleus area of keratinocytes were decreased by the follistatin treatment compared to the cells in irradiated skin of control mice. Finally, the gene expression of transforming growth factor β1 (Tgfb1), and smooth muscle actin (Acta2) were decreased in the irradiated skin and Acta2 and inhibin βA subunit (Inhba) were decreased in the irradiated muscle of the follistatin treated mice. Follistatin attenuated the radiation-induced fibrotic response in irradiated mice. These studies provide the data to support further investigation of the use of follistatin to reduce radiation-induced fibrosis in patients undergoing radiotherapy for cancer.

  15. Familial papular epidermal nevus with "skyline" basal cell layer.

    PubMed

    Brena, Michela; Besagni, Francesca; Boneschi, Vinicio; Tadini, Gianluca

    2014-01-01

    Papular epidermal nevus with "skyline" basal cell layer (PENS), a novel keratinocytic nevus, has recently been described as a mosaic condition with varying presentations. We herein describe typical PENS lesions, which usually occur sporadically, affecting two members of the same family. The concept of paradominant inheritance is proposed to explain the paradox of occasional transmission of normally sporadically occurring traits.

  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. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  17. Epidermal electronics with advanced capabilities in near-field communication.

    PubMed

    Kim, Jeonghyun; Banks, Anthony; Cheng, Huanyu; Xie, Zhaoqian; Xu, Sheng; Jang, Kyung-In; Lee, Jung Woo; Liu, Zhuangjian; Gutruf, Philipp; Huang, Xian; Wei, Pinghung; Liu, Fei; Li, Kan; Dalal, Mitul; Ghaffari, Roozbeh; Feng, Xue; Huang, Yonggang; Gupta, Sanjay; Paik, Ungyu; Rogers, John A

    2015-02-25

    Epidermal electronics with advanced capabilities in near field communications (NFC) are presented. The systems include stretchable coils and thinned NFC chips on thin, low modulus stretchable adhesives, to allow seamless, conformal contact with the skin and simultaneous capabilities for wireless interfaces to any standard, NFC-enabled smartphone, even under extreme deformation and after/during normal daily activities.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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 ...

  3. Asset Management and Facility Equipment Maintenance Nexus: Maintenance Effectiveness

    DTIC Science & Technology

    2013-09-01

    1000 Under Project #371013, “Linking FEM and Asset Management” ERDC TR-13-16 ii Abstract The US Army Corps of Engineers (USACE) has constructed...how data col- lected in Facility Equipment Maintenance ( FEM ) can be used to evaluate the effectiveness of maintenance to improve the condition of...lock infra- structure components. This includes analyzing how data already being col- lected in FEM can be used to evaluate maintenance effectiveness and

  4. Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration

    PubMed Central

    de la Garza-Rodea, Anabel S; Boersma, Hester; Dambrot, Cheryl; de Vries, Antoine AF; van Bekkum, Dirk W; Knaän-Shanzer, Shoshan

    2015-01-01

    -vascularized periphery of the implants. The contribution of human MSCs to murine myofiber formation was, however, restricted to the cryopreserved mouse muscle implants. This suggests that fresh murine muscle tissue provides a suboptimal environment for maintenance of human MSCs. A detailed analysis of the histological sections of the various muscle implants revealed the presence of cellular structures with a deviating morphology. Additional stainings with alizarin red and alcian blue showed myofiber calcification in 50 of 66 human muscle implants, and encapsulated cartilage in 10 of 81 of murine muscle implants, respectively. CONCLUSION: In mouse models the engagement of human MSCs in myoregeneration might be underestimated. Furthermore, our model permits the dissection of species-specific factors in the microenvironment. PMID:25992329

  5. Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration.

    PubMed

    de la Garza-Rodea, Anabel S; Boersma, Hester; Dambrot, Cheryl; de Vries, Antoine Af; van Bekkum, Dirk W; Knaän-Shanzer, Shoshan

    2015-05-20

    the implants. The contribution of human MSCs to murine myofiber formation was, however, restricted to the cryopreserved mouse muscle implants. This suggests that fresh murine muscle tissue provides a suboptimal environment for maintenance of human MSCs. A detailed analysis of the histological sections of the various muscle implants revealed the presence of cellular structures with a deviating morphology. Additional stainings with alizarin red and alcian blue showed myofiber calcification in 50 of 66 human muscle implants, and encapsulated cartilage in 10 of 81 of murine muscle implants, respectively. In mouse models the engagement of human MSCs in myoregeneration might be underestimated. Furthermore, our model permits the dissection of species-specific factors in the microenvironment.

  6. Harnessing the power of maintenance

    SciTech Connect

    Toomey, G.

    2006-03-15

    More electric utilities are realizing that structured, comprehensive and proactive maintenance strategies deliver uptime to their bottom line. The article presents four case studies illustrating some of the available solutions to coal and gas-fired plant maintenance. These were: a maintenance strategy review of five coal fired and 22 gas-fired units to identify the importance of equipment along with maintenance tasks; a predictive maintenance program monitoring vibration to detect machine fault conditions including bearing condition; setting up a network to monitor data from several coal- and gas-fired plants at one central location; and creating a maintenance strategy to cushion against the possibility of unscheduled downtime and imposed penalties. 2 photos.

  7. 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.

  8. Maintenance Strategy Maximising Availability Rate

    NASA Astrophysics Data System (ADS)

    Rosiński, Adam

    2012-12-01

    Electronic equipment operates under various conditions. Due to characteristic nature of its applications (e.g. in transport), it should be highly reliable. Many years’ worth of observations show, those systems not only require their constituting parts to function up to par, but also their maintenance has to be efficiently managed. This paper presents maintenance strategies and particularly focuses on maintenance strategy enabling maximising the availability rate.

  9. Boiler Combustion Control Maintenance Manual.

    DTIC Science & Technology

    1983-03-01

    controller and the final control element, as shown in Figure 6-1. The maintenance basically involves the inspection of the poppet valve in the relay...routine maintenance of this component basically involves placing a few drops of light machine oil on the ball bearing fulcrum. The poppet valve should... Valve /Air Damper Positioners ................................ 6-2 7.0 ELECTRIC PARALLEL POSITIONING CONTROL MAINTENANCE ................ 7-1 8.0 MOBILE

  10. Buildings Lean Maintenance Implementation Model

    NASA Astrophysics Data System (ADS)

    Abreu, Antonio; Calado, João; Requeijo, José

    2016-11-01

    Nowadays, companies in global markets have to achieve high levels of performance and competitiveness to stay "alive".Within this assumption, the building maintenance cannot be done in a casual and improvised way due to the costs related. Starting with some discussion about lean management and building maintenance, this paper introduces a model to support the Lean Building Maintenance (LBM) approach. Finally based on a real case study from a Portuguese company, the benefits, challenges and difficulties are presented and discussed.

  11. 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.

  12. Towards Agile Ontology Maintenance

    NASA Astrophysics Data System (ADS)

    Luczak-Rösch, Markus

    Ontologies are an appropriate means to represent knowledge on the Web. Research on ontology engineering reached practices for an integrative lifecycle support. However, a broader success of ontologies in Web-based information systems remains unreached while the more lightweight semantic approaches are rather successful. We assume, paired with the emerging trend of services and microservices on the Web, new dynamic scenarios gain momentum in which a shared knowledge base is made available to several dynamically changing services with disparate requirements. Our work envisions a step towards such a dynamic scenario in which an ontology adapts to the requirements of the accessing services and applications as well as the user's needs in an agile way and reduces the experts' involvement in ontology maintenance processes.

  13. 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.

  14. 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.

  15. Benzo(a)pyrene metabolism in primary cultures of mouse epidermal cells and untransformed and transformed epidermal cell lines.

    PubMed

    DiGiovanni, J; Miller, D R; Singer, J M; Viaje, A; Slaga, T J

    1982-07-01

    The metabolism of [3H]benzo(a)pyrene [B(a)P] by cultures of primary mouse epidermal cells and untransformed and transformed epidermal cell lines was investigated. All three cell types effectively metabolized [3H]B(a)P. The major organic solvent-extractable metabolites found intracellularly in primary cultures were trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene, although quantities of 9-hydroxybenzo(a)pyrene, trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene, and quinones also were present. The major organic solvent-soluble metabolites found in the extracellular medium were trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene and trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, with smaller quantities of unconjugated phenols and quinones. The major water-soluble metabolites found in the extracellular medium were conjugated with glucuronic acid [primarily 3-hydroxybenzo(a)pyrene and several quinones]. No sulfate conjugates of [3H]B(a)P metabolites were detected. [3H]B(a)P metabolism was similar in cultures of untransformed and transformed epidermal cell lines but differed from the primary cultures. The major intracellular and extracellular organic solvent-soluble metabolites were diols. Little or no unconjugated phenols were detected. Both the untransformed and transformed epidermal cell lines converted [3H]B(a)P to water-soluble metabolites, primarily glucuronide conjugates. In contrast to the primary cells, a major pathway of trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene metabolism in the untransformed and transformed cell lines was a glucuronide conjugate. Primary mouse epidermal cells provide an important model system for studying factors affecting the activation and detoxification of hydrocarbon carcinogens.

  16. 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.

  17. 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…

  18. High affinity nanobodies against human epidermal growth factor receptor selected on cells by E. coli display.

    PubMed

    Salema, Valencio; Mañas, Carmen; Cerdán, Lidia; Piñero-Lambea, Carlos; Marín, Elvira; Roovers, Rob C; Van Bergen En Henegouwen, Paul M P; Fernández, Luis Ángel

    2016-10-01

    Most therapeutic antibodies (Abs) target cell surface proteins on tumor and immune cells. Cloning of Ab gene libraries in E. coli and their display on bacteriophages is commonly used to select novel therapeutic Abs binding target antigens, either purified or expressed on cells. However, the sticky nature of bacteriophages renders phage display selections on cells challenging. We previously reported an E. coli display system for expression of VHHs (i.e., nanobodies, Nbs) on the surface of bacteria and selection of high-affinity clones by magnetic cell sorting (MACS). Here, we demonstrate that E. coli display is also an attractive method for isolation of Nbs against cell surface antigens, such as the epidermal growth factor receptor (EGFR), upon direct selection and screening of Ab libraries on live cells. We employ a whole cell-based strategy using a VHH library obtained by immunization with human tumor cells over-expressing EGFR (i.e., A431), and selection of bacterial clones bound to murine fibroblast NIH-3T3 cells transfected with human EGFR, after depletion of non-specific clones on untransfected cells. This strategy resulted in the isolation of high-affinity Nbs binding distinct epitopes of EGFR, including Nbs competing with the ligand, EGF, as characterized by flow cytometry of bacteria displaying the Nbs and binding assays with purified Nbs using surface plasmon resonance. Hence, our study demonstrates that E. coli display of VHH libraries and selection on cells enables efficient isolation and characterization of high-affinity Nbs against cell surface antigens.

  19. High affinity nanobodies against human epidermal growth factor receptor selected on cells by E. coli display

    PubMed Central

    Salema, Valencio; Mañas, Carmen; Cerdán, Lidia; Piñero-Lambea, Carlos; Marín, Elvira; Roovers, Rob C.; Van Bergen en Henegouwen, Paul M.P.; Fernández, Luis Ángel

    2016-01-01

    ABSTRACT Most therapeutic antibodies (Abs) target cell surface proteins on tumor and immune cells. Cloning of Ab gene libraries in E. coli and their display on bacteriophages is commonly used to select novel therapeutic Abs binding target antigens, either purified or expressed on cells. However, the sticky nature of bacteriophages renders phage display selections on cells challenging. We previously reported an E. coli display system for expression of VHHs (i.e., nanobodies, Nbs) on the surface of bacteria and selection of high-affinity clones by magnetic cell sorting (MACS). Here, we demonstrate that E. coli display is also an attractive method for isolation of Nbs against cell surface antigens, such as the epidermal growth factor receptor (EGFR), upon direct selection and screening of Ab libraries on live cells. We employ a whole cell-based strategy using a VHH library obtained by immunization with human tumor cells over-expressing EGFR (i.e., A431), and selection of bacterial clones bound to murine fibroblast NIH-3T3 cells transfected with human EGFR, after depletion of non-specific clones on untransfected cells. This strategy resulted in the isolation of high-affinity Nbs binding distinct epitopes of EGFR, including Nbs competing with the ligand, EGF, as characterized by flow cytometry of bacteria displaying the Nbs and binding assays with purified Nbs using surface plasmon resonance. Hence, our study demonstrates that E. coli display of VHH libraries and selection on cells enables efficient isolation and characterization of high-affinity Nbs against cell surface antigens. PMID:27472381

  20. 14 CFR 121.367 - Maintenance, preventive maintenance, and alterations programs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Maintenance, preventive maintenance, and..., Preventive Maintenance, and Alterations § 121.367 Maintenance, preventive maintenance, and alterations..., preventive maintenance, and alterations that ensures that— (a) Maintenance, preventive......

  1. 14 CFR 135.433 - Maintenance and preventive maintenance training program.

    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... SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.433 Maintenance and preventive maintenance training program. Each certificate holder or a person performing maintenance or...

  2. 14 CFR 121.367 - Maintenance, preventive maintenance, and alterations programs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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  3. 14 CFR 121.367 - Maintenance, preventive maintenance, and alterations programs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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  4. 14 CFR 121.367 - Maintenance, preventive maintenance, and alterations programs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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  5. 14 CFR 121.367 - Maintenance, preventive maintenance, and alterations programs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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  6. 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

  7. Isolation and Differentiation of Murine Macrophages.

    PubMed

    Rios, Francisco J; Touyz, Rhian M; Montezano, Augusto C

    2017-01-01

    Macrophages play a major role in inflammation, wound healing, and tissue repair. Infiltrated monocytes differentiate into different macrophage subtypes with protective or pathogenic activities in vascular lesions. In the heart and vascular tissues, pathological activation promotes cardiovascular inflammation and remodeling and there is increasing evidence that macrophages play important mechanisms in this environment. Primary murine macrophages can be obtained from: bone marrow by different treatments (granulocyte-macrophage colony-stimulating factor-GM-CSF, macrophage colony-stimulating factor-M-CSF or supernatant of murine fibroblast L929), peritoneal cavity (resident or thioglycolate elicit macrophages), from the lung (alveolar macrophages) or from adipose tissue. In this chapter we describe some protocols to obtain primary murine macrophages and how to identify a pure macrophage population or activation phenotypes using different markers.

  8. De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells.

    PubMed

    Pontiggia, Luca; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Oliveira, Carol; Braziulis, Erik; Klar, Agnieszka S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

    2014-06-01

    In our previous work, we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both secretory and absorptive sweat gland cell subpopulations. We demonstrate the superiority of secretory over absorptive cells in forming a new epidermis on two levels: first, the proliferative and colony-forming efficiencies in vitro are significantly higher for secretory cells (SCs), and second, SCs show a higher frequency of successful epidermis formation as well as an increase in the thickness of the formed epidermis in the in vitro and in vivo functional analyses using a 3D dermo-epidermal skin model. However, the ability of forming functional skin substitutes is not limited to SCs, which supports the hypothesis that multiple subtypes of sweat gland epithelial cells hold regenerative properties, while the existence and exact localization of a keratinocyte stem cell population in the human eccrine sweat gland remain elusive.

  9. A look at epidermal barrier function in atopic dermatitis: physiologic lipid replacement and the role of ceramides.

    PubMed

    Sajić, D; Asiniwasis, R; Skotnicki-Grant, S

    2012-07-01

    This review summarizes and discusses the role and efficacy of moisturizers, particularly the more recently introduced ceramide-based formulations, in the skin care regimen of patients with both active and quiescent atopic dermatitis (AD). It is now well established that a complex interplay of environmental and genetic factors are responsible for disease onset and chronicity. Indeed, several novel genetic mechanisms have been recently discovered to be associated with AD pathogenesis. Moreover, it is increasingly recognized that the epidermal barrier plays a critical role in the initiation, perpetuation, and exacerbation of AD. The skin of patients with AD harbors several defects in epidermal barrier function, including filaggrin and ceramides. An improved understanding of these etiopathogenic factors has led to the development of topical ceramide-dominant moisturizers to replace the deficient molecules and re-establish the integrity of barrier defenses. Some of these products have demonstrated efficacy in the treatment of adult and childhood AD that are similar to mid-potency topical steroids. More importantly, they have been shown to be safe with very few associated side-effects. We recommend the addition of such new agents as both the first step of treatment and in the maintenance of clinically quiescent skin of patients with AD.

  10. 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.

  11. 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.

  12. 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)

  13. Preservation and Maintenance of Maps

    ERIC Educational Resources Information Center

    Capps, Marie T.

    1972-01-01

    The problems of storage and maintenance which confront the map librarian are discussed. Included are the causes of map damage and deterioration, methods of detection and correction, and suggestions of further measures for optimum preservation. Useful guides on preservation and maintenance are cited. (7 references) (Author/NH)

  14. Automated System Programs Preventive Maintenance.

    ERIC Educational Resources Information Center

    Locke, Richard C.

    1987-01-01

    A preventive maintenance system provides for the monitoring and inspection of school building elements in a programmed way through an automatic checklist. Utility cost savings are expected along with reduction of travel and wait time, and measurable standards of performance for all maintenance and repair work. (MLF)

  15. Preventive Maintenance Handbook. Audiovisual Equipment.

    ERIC Educational Resources Information Center

    Educational Products Information Exchange Inst., Stony Brook, NY.

    The preventive maintenance system for audiovisual equipment presented in this handbook is designed by specialists so that it can be used by nonspecialists in school sites. The report offers specific advice on saftey factors and also lists major problems that should not be handled by nonspecialists. Other aspects of a preventive maintenance system…

  16. Modern Method for Preventive Maintenance

    ERIC Educational Resources Information Center

    Wilson, Howard D.

    1974-01-01

    Describes a system at Michigan State University that comprises 16 separate programs and schedules 25,000 manhours of preventive maintenance. With information about preventive maintenance for over 100,000 units stored in its computer, the university saves personnel, time, and energy. (Author/MLF)

  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. Truth Maintenance in Automatic Planning.

    DTIC Science & Technology

    The objective of this project was to explore the usefulness of incorporating truth maintenance system (TMS) technology into the design of planning...in the report. The six appendices describe the underlying research contributing to the design of the prototype system. Keywords: Truth maintenance, Planning search, Replanning, Nonmonotonic reasoning, Defeasible reasoning.

  19. Achieving world class maintenance status

    SciTech Connect

    Tomlingson, P.D.

    2007-08-15

    The article written by a management consultant, discusses the art of successful planning and operation of maintenance in mines considering factors such as benchmaking, key performance indices (KPIs) and frequency of procedures which can help achieve 'world class maintenance'. 1 fig.

  20. 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)

  1. Preventative maintenance for control systems

    SciTech Connect

    Corbett, G.O.

    1985-05-01

    Preventative maintenance of the control systems should be performed on a required interval. Most manufacturers specify six to twelve month intervals. However, inspections can often be accomplished when the control units or mechanical systems are out of service for a malfunction repair. A procedural checklist for proper maintenance is given.

  2. 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.

  3. 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

  4. 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

  5. Effects of ozone in normal human epidermal keratinocytes.

    PubMed

    McCarthy, James T; Pelle, Edward; Dong, Kelly; Brahmbhatt, Krupa; Yarosh, Dan; Pernodet, Nadine

    2013-05-01

    Ozone is a tropospheric pollutant that can form at ground level as a result of an interaction between sunlight and hydrocarbon engine emissions. As ozone is an extremely oxidative reaction product, epidermal cells are in the outer layer of defense against ozone. We exposed normal human epidermal keratinocytes (NHEK) to concentrations of ozone that have been measured in cities and assayed for its effects. Hydrogen peroxide and IL-1α levels both increased while ATP levels decreased. We found a decrease in the NAD-dependent histone deacetylase, sirtuin 3. Lastly, we found that ozone increased DNA damage as evaluated by Comet assay. Taken together, our results show increased damage to NHEK that will ultimately impair normal cellular function as a result of an environmentally relevant ozone exposure. © 2013 John Wiley & Sons A/S.

  6. Toxic epidermal necrolysis - management issues and treatment options.

    PubMed

    Widgerow, Alan D

    2011-01-01

    Toxic epidermal necrolysis (TEN) and Steven-Johnson syndrome (SJS) are characterized by extensive necrosis and cleavage of the epidermis from the dermis akin to a superficial or partial thickness burn. Sepsis is the usual cause of mortality but much of the pathophysiologic process results from an outpouring of cytokines and matrixmetalloproteinases (MMPs) which have a destructive effect on the extracellular matrix and may play a part in the epidermal/dermal cleavage seen with this disease. Recent attention has been focused on the modulation of proteases in an attempt to decrease the MMP-mediated destruction. Nanocrystalline silver (NCS) is one such agent that has good anti-microbial efficacy, but is also effective in modulating MMP levels. Twelve cases of confirmed TEN that were treated with NCS were analyzed with a view to assessing efficacy and setting logical guidelines for managing this condition, particularly in relation to immunosupressed patients. From this study important issues have been highlighted for discussion.

  7. Cell growth and differentiation in Arabidopsis epidermal cells.

    PubMed

    Guimil, Sonia; Dunand, Christophe

    2007-01-01

    Plant epidermal cells are morphologically diverse, differing in size, shape, and function. Their unique morphologies reflect the integral function each cell performs in the organ to which it belongs. Cell morphogenesis involves multiple cellular processes acting in concert to create specialized shapes. The Arabidopsis epidermis contains numerous cell types greatly differing in shape, size, and function. Work on three types of epidermal cells, namely trichomes, root hairs, and pavement cells, has made significant progress towards understanding how plant cells reach their final morphology. These three cell types have highly distinct morphologies and each has become a model cell for the study of morphological processes. A growing body of knowledge is creating a picture of how endoreduplication, cytoskeletal dynamics, vesicle transport, and small GTPase signalling, work in concert to create specialized shapes. Similar mechanisms that determine cell shape and polarity are shared between these cell types, while certain mechanisms remain specific to each.

  8. Acetaminophen induced Steven Johnson syndrome-toxic epidermal necrolysis overlap.

    PubMed

    Khawaja, Ali; Shahab, Ahmed; Hussain, Syed Ather

    2012-05-01

    Steven Johnson Syndrome and Toxic Epidermal Necrolysis are rare but severe form of hypersensitivity inflammatory reactions to multiple offending agents including drugs. Acetaminophen is extensively used due to its analgesic and anti-pyretic properties. It is rendered to be relatively safe, with hepatotoxicity considered to be the major adverse effect. However, very few cases of Steven Johnson Syndrome and Toxic Epidermal Necrolysis have been reported with acetaminophen usage in the past. We present the case of a 40 years old lady who developed an overlap of the two condition after taking several doses of acetaminophen for fever. She presented with widespread maculopapular rash, stinging in the eyes, oral mucosal ulcerations and high grade fever. She was successfully treated with corticosteroid therapy along with the supportive treatment. This case addresses the fact, that severe hypersensitivity reactions can occur with acetaminophen which can be potentially life threatening.

  9. Regulation of mitotic spindle orientation during epidermal stratification.

    PubMed

    Xie, Wei; Zhou, Jun

    2016-12-20

    The epidermis is a stratified epithelium that serves as a barrier to infection from environmental pathogens and prevents water loss. Epidermal stratification is tightly controlled during embryogenesis. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance the growth of the skin surface area against the generation of differentiated cell layers. Therefore, understanding the relationship between oriented divisions of progenitor cells and the development and stratification of the epidermis is of paramount importance in the field of skin biology and pathology. We provide here an integrated view of recent studies implicating that improper orientation of the mitotic spindle contributes to disorders associated with abnormal epidermal stratification and suggesting that spindle orientation could serve as a potential therapeutic target in skin diseases.

  10. 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.

  11. Ileal involvement in toxic epidermal necrolysis (Lyell syndrome).

    PubMed

    Michel, P; Joly, P; Ducrotte, P; Hemet, J; Leblanc, I; Lauret, P; Lerebours, E; Colin, R

    1993-10-01

    Intestinal involvement in toxic epidermal necrolysis (TEN) has been identified only rarely. This report describes a case of TEN with ileal manifestations characterized by a profuse diarrhea with malabsorption, protein-losing enteropathy, and radiologically by multiple stenosis. After healing of the cutaneous lesions, total parenteral nutrition was initiated, resulting in a decreased diarrhea. However, after one month of total parenteral nutrition, malabsorption and protein-losing enteropathy continued and the radiological lesions were still present with an aspect consistent with a sclerotic process. A surgical resection of the pathological ileal segment was performed with end-to-end anastomosis. Pathological examination of the resected segment showed a necrosis of the ileal mucosa with a pattern similar to that of the epidermal necrosis. No sclerosis was observed. It seems that a prolonged total parenteral nutrition could have induced a complete healing of intestinal lesions. This case report is the first clinical, radiological, and histological study of an ileal involvement in TEN.

  12. 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.

  13. "Cut-and-Paste" Manufacture of Multiparametric Epidermal Sensor Systems.

    PubMed

    Yang, Shixuan; Chen, Ying-Chen; Nicolini, Luke; Pasupathy, Praveenkumar; Sacks, Jacob; Su, Becky; Yang, Russell; Sanchez, Daniel; Chang, Yao-Feng; Wang, Pulin; Schnyer, David; Neikirk, Dean; Lu, Nanshu

    2015-11-04

    Multifunctional epidermal sensor systems (ESS) are manufactured with a highly cost and time effective, benchtop, and large-area "cut-and-paste" method. The ESS made out of thin and stretchable metal and conductive polymer ribbons can be noninvasively laminated onto the skin surface to sense electrophysiological signals, skin temperature, skin hydration, and respiratory rate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. 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

  15. Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis.

    PubMed

    Caruso, Roberta; Botti, Elisabetta; Sarra, Massimiliano; Esposito, Maria; Stolfi, Carmine; Diluvio, Laura; Giustizieri, Maria Laura; Pacciani, Valentina; Mazzotta, Annamaria; Campione, Elena; Macdonald, Thomas T; Chimenti, Sergio; Pallone, Francesco; Costanzo, Antonio; Monteleone, Giovanni

    2009-09-01

    T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.

  16. 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.

  17. 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.

  18. 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.

  19. Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

    PubMed

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

    2015-03-01

    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.

  20. 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

  1. 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

  2. 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.

  3. Epidermal nevus syndrome with hypophosphatemic rickets in a young girl.

    PubMed

    Sukkhojaiwaratkul, Dabuswinee; Mahachoklertwattana, Pat; Poomthavorn, Preamrudee

    2014-07-01

    Epidermal nevus syndrome (ENS) is a rare congenital disorder. It is characterised by epidermal nevi and abnormalities of multiple organs, including central nervous system, skeleton, cardiovascular and genitourinary systems and eyes. Hypophosphatemic rickets-associated ENS has rarely been reported. We report a 46-month-old girl who presented with a classical feature of hypophosphatemic rickets. Examination of skin revealed multiple melanocytic nevi at her trunk, face and both arms with verrucous plaques at both axillae and neck, and yellow plaques at the back along Blaschko's lines. Histopathology of the skin lesions was compatible with epidermal nevi and nevus sebaceous. Therefore, the diagnosis of ENS was made. Apart from typical rickets, the skeletal X-rays interestingly displayed fibrous dysplasia-like lesions along right femur, tibia and fibula. Hypophosphatemic rickets was treated with alfacalcidol and phosphate solution. After 3 months of treatment, clinical improvement of hypophosphatemic rickets was clearly demonstrated. Her blood chemistries were normalised at 5 months following the treatment. In conclusion, hypophosphatemic rickets is a rare presentation of ENS. Our patient also demonstrated an additional abnormal bone finding, fibrous dysplasia-like lesions, associated with rachitic changes. This highlights heterogeneity of this condition and importance of thorough evaluation of patients with ENS. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  4. Protein composition of cornified cell envelopes of epidermal keratinocytes.

    PubMed

    Steven, A C; Steinert, P M

    1994-02-01

    Terminally differentiated mammalian epidermal cells are lined with a 15 nm thick layer of proteins cross-linked by isodipeptide and disulfide bonds, called the cornified cell envelope (CE). A number of proteins, including involucrin, loricrin, cystatin A, filaggrin, a cysteine-rich protein (CRP) and the 'small proline-rich' proteins (SPRRs) have been reported to be components of this complex, but little information has been obtained as to their relative abundances because the acute insolubility of the CEs has precluded direct methods of analysis. To address this question, we have determined the amino acid compositions of isolated CEs, and then modelled them in terms of linear combinations of the candidate proteins. The results show that stratum corneum CEs have a loricrin content of 65-70% (w/w) in human, and 80-85% in mouse. In human epidermal CEs, the secondary contributors are filaggrin and CRP (each approximately 10%), with smaller amounts of involucrin, SPRR and cystatin A (2-5% each) also present. Mouse epidermal CEs have about the same amount of filaggrin and somewhat more SPRR, but only trace amounts of the other proteins. In marked contrast, the major constituents of the CEs of cultured keratinocytes induced to terminal differentiation in vitro are cystatin A, involucrin and CRP (each approximately 30%). No significant amount of loricrin was detected except in sloughed mouse cells, which represent a more advanced state of terminal differentiation than attached cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Nrf2 links epidermal barrier function with antioxidant defense

    PubMed Central

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

    2012-01-01

    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

  6. Ultraviolet radiation augments epidermal beta-adrenergic adenylate cyclase response

    SciTech Connect

    Iizuka, H.; Kajita, S.; Ohkawara, A.

    1985-05-01

    Pig skin was irradiated in vivo with fluorescent sunlamp tubes (peak emission at 305 nm). A significant increase in epidermal beta-adrenergic adenylate cyclase response was observed as early as 12 h following 1-2 minimum erythema doses (MEDs) UVB exposure, which lasted at least 48 h. The augmentation of adenylate cyclase response was relatively specific to the beta-adrenergic system and there was no significant difference in either adenosine- or histamine-adenylate cyclase response of epidermis. The increased beta-adrenergic adenylate cyclase response was less marked at higher doses of UVB exposure (5 MEDs); in the latter condition, a significant reduction in adenosine- or histamine-adenylate cyclase response was observed. There was no significant difference in either low- or high-Km cyclic AMP phosphodiesterase activity between control and UVB-treated skin at 1-2 MEDs. These data indicate that the epidermal adenylate cyclase responses are affected in vivo by UVB irradiation, which might be a significant regulatory mechanism of epidermal cyclic AMP systems.

  7. Characterization of powdered epidermal vaccine delivery with multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Mulholland, William J.; Kendall, Mark A. F.; White, Nick; Bellhouse, Brian J.

    2004-11-01

    Multiphoton laser scanning microscopy (MPLSM) has been adapted to non-invasively characterize hand-held powdered epidermal vaccine delivery technology. A near infrared femtosecond pulsed laser, wavelength at approximately 920 nm, was used to evoke autofluorescence of endogenous fluorophores within ex vivo porcine and human skin. Consequently, sub cellular resolution three-dimensional images of stratum corneum and viable epidermal cells were acquired and utilized to observe the morphological deformation of these cells as a result of micro-particle penetration. Furthermore, the distributional pattern of micro-particles within the specific skin target volume was quantified by measuring the penetration depth as revealed by serial optical sections in the axial plane obtained with MPLSM. Additionally, endogenous fluorescence contrast images acquired at the supra-basal layer reveal cellular structures that may pertain to dendritic Langerhans cells of the epidermis. These results show that MPLSM has advantages over conventional histological approaches, since three-dimensional functional images with sub-cellular spatial resolution to depths beyond the epidermis can be acquired non-invasively. Accordingly, we propose that MPLSM is ideal for investigations of powdered epidermal vaccine delivery.

  8. Psoralens and coumarins for receptor targeting on epidermal cells

    SciTech Connect

    Jetter, M.M.

    1989-01-01

    Specific binding sites have been identified for the psoralens, discrete from DNA, in different epidermal cell lines. These receptors are saturable and are alkylated by the action of psoralens + UVA light. A psoralen receptor has been partially purified and established to be a protein of approximately 20,000 daltons. Inhibition of the binding of epidermal growth factor to its receptor and inhibition of the tyrosine kinase activity of the EGF receptor has been associated with PUVA treatment. These findings conflict with the general assumption that the biological effects of psoralens as photoactive compounds are associated with their ability to covalently bind to and crosslink DNA. In collaboration with Laskin's,laboratory, several classes of psoralen agonists were synthesized. These compounds include coumarins, furocoumarin and benzodipyran-2-one derivatives. The methods of preparation were varied and include variants of the Claisen rearrangement, acid and base-catalyzed condensations. The synthesized compounds were tested for their potential inhibition of {sup 125}I-EGF receptor binding. It was discovered that many of these agents showed potent inhibition activity similar to the psoralens. This data offers the possibility that sites of action, other than DNA, are involved in the mechanism by which photoactivated psoralens modulate epidermal cell lines.

  9. Precoccygeal epidermal inclusion cyst: ultrasound and MR imaging features.

    PubMed

    Halefoglu, A M; Sen, E Y

    2012-01-01

    In this case report, we are presenting a 33 year-old pregnant woman who suffered from pelvic and coccygeal pain. Her medical examination and laboratory tests were found within normal limits. In order to explain her pain, initially a pelvic ultrasound was performed which revealed a huge hypoechoic cystic mass in the precoccygeal-presacral region. She then underwent a pelvic magnetic resonance imaging (MRI) examination in order to better delineate the characteristics and extension of this huge mass. On these images the mass was hypointense on T1 weighted images and extremely hyperintense on T2 weighted images. We also performed a diffusion weighted sequence which exhibited high signal intensity for the mass. We thought that this finding could be suggestive of an epidermal inclusion cyst similar to that of a brain epidermoid cyst which shows bright signal intensity on diffusion weighted images. The patient was operated and the cystic mass removed from the precoccygeal region. Histopathological examination confirmed the diagnosis of epidermal inclusion cyst. This case report suggests that an epidermal inclusion cyst should be considered in the differential diagnosis of intractable pelvic and coccygeal pain. MRI can help to establish the correct diagnosis.

  10. Leukemia cutis in association with cutaneous epidermal malignancies.

    PubMed

    Ra, Seong; Su, Albert; Ellison, Doug; Koperski, Judith; Bonilla, Maria; Robbins, Bruce

    2012-10-01

    Epidermal malignancies developing in association with hematolymphoid malignancies are exceptional. Only one prior case of myeloid leukemia cutis with a cutaneous epidermal malignancy has been reported. We report two cases; one occurred in association with squamous cell carcinoma (SCC) and another with basal cell carcinoma (BCC). Both patients were 83-year-old males without established histories of systemic hematopoietic disorders; one presented with an erythematous papule on the right upper back and the other with a nodule on the left wrist. One biopsy revealed nodular BCC with an associated perivascular myeloid leukemic infiltrate showing immunohistochemical positivity for CD43 and CD45. The other biopsy showed SCC associated with a leukemic infiltrate in sheets with myeloid blasts, eosinophilic myelocytes and maturing myeloid precursors. The myeloid cells showed immunohistochemical expression of CD43, CD68, CD33, CD117 and myeloperoxidase. Both patients had myeloblasts on peripheral blood smear. One patient declined further treatment and died of disease 5 weeks after the initial biopsy. The other patient underwent chemotherapy and is alive after 6 months. Although most inflammatory infiltrates associated with cutaneous epidermal malignancies are reactive, careful examination is necessary to exclude systemic hematopoietic disease, especially in elderly patients. Copyright © 2012 John Wiley & Sons A/S.

  11. 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

  12. 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

  13. Epidermal cell proliferation and promoting ability of phorbol esters.

    PubMed

    Slaga, T J; Scribner, J D; Viaje, A

    1976-11-01

    Dose-response relationships on the abilities of several phorbol ester tumor promoters to promote skin tumors after 7,12-dimethylbenz[a]anthracene initiation and to bring about edema, inflammation, and epidermal hyperplasia were determined in female Charles River CD-1 mice. The promoting ability of the potent synthetic promoter, phorbol-12,13-dioctanoate (PdiC8), was determined over a dose range of 0.1-10 mug/application. Administration of PdiC8 two times weekly at dosages of 4, 6, 8, and 10 mug gave little variation in tumor response. A dose-dependent tumor response occurred at doses of 1-4 mug PdiC8. Only 1 papilloma was observed when PdiC8 was given twice weekly at a dose of 0.1 or 0.5 mug. A similar dose-response relation was observed for the ability of PdiC8 to stimulate epidermal hyperplasia. Investigations of other phorbol esters revealed an excellent correlation between their promoting ability and their ability to induce epidermal hyperplasia; however, that was not the case for compounds outside the phorbol ester series (i.e., acetic acid, cantharidin, and ethylphenylpropiolate).

  14. 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. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. 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....

  16. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Maintenance, Preventive Maintenance... specified in paragraph (b) of this section: (1) Records of the maintenance, preventive maintenance, and... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Maintenance records. 91.417 Section...

  17. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Maintenance, Preventive Maintenance... specified in paragraph (b) of this section: (1) Records of the maintenance, preventive maintenance, and... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Maintenance records. 91.417 Section...

  18. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Maintenance, Preventive Maintenance... specified in paragraph (b) of this section: (1) Records of the maintenance, preventive maintenance, and... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Maintenance records. 91.417 Section...

  19. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Maintenance, Preventive Maintenance... specified in paragraph (b) of this section: (1) Records of the maintenance, preventive maintenance, and... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Maintenance records. 91.417 Section...

  20. Role of pili in the adherence of Pseudomonas aeruginosa to mouse epidermal cells.

    PubMed Central

    Sato, H; Okinaga, K

    1987-01-01

    Pili have been demonstrated to be the adhesins of Pseudomonas aeruginosa for mouse epidermal cells. The mechanisms of adhesion of P. aeruginosa to mouse epidermal cells was studied by using four mutants derived from a single strain: flagellated and piliated (F+P+), flagellated and nonpiliated (F+P-), nonflagellated and piliated (F-P+), and nonflagellated and nonpiliated (F-P-) mutants. F+P+ and F-P+ bacteria efficiently adhered to mouse epidermal cells, while F+P- and F-P- bacteria hardly adhered to mouse epidermal cells. The number of F+P+ bacteria that adhered to mouse epidermal cells was almost the same as that of F-P+ bacteria. The number of F+P- bacteria that adhered to mouse epidermal cells was almost the same as that of F-P- bacteria. The adhesion of P+ (F+P+ and F-P+) bacteria was inhibited by antipilus serum, while that of P- (F+P- and F-P-) bacteria was not inhibited by antipilus serum. There were no significant differences between the number of bacteria adhering to mouse epidermal cells isolated from normal skin and those adhering to cells isolated from burned skin. Heating of the mouse epidermal cell suspension had no effect on the adhesion of P. aeruginosa. These results suggest that pili mediate the adhesion of P. aeruginosa to mouse epidermal cells and that P. aeruginosa adheres efficiently to mouse epidermal cells despite the loss of cell viability caused by burning. PMID:2886430

  1. Commonly dysregulated genes in murine APL cells

    PubMed Central

    Yuan, Wenlin; Payton, Jacqueline E.; Holt, Matthew S.; Link, Daniel C.; Watson, Mark A.; DiPersio, John F.; Ley, Timothy J.

    2007-01-01

    To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly expressed in restricted developmental “windows,” suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RARα under control of the murine cathepsin G locus. While many promyelocyte-specific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid cells from the same mouse model, suggesting that dysregulation occurs as a “downstream” event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis. PMID:17008535

  2. Murine typhus in child, Yucatan, Mexico.

    PubMed

    Zavala-Castro, Jorge E; Zavala-Velázquez, Jorge E; Sulú Uicab, Justo Eduardo

    2009-06-01

    A case of murine typhus in Yucatan was diagnosed in a child with nonspecific signs and symptoms. The finding of Rickettsia typhi increases the number of Rickettsia species identified in Yucatan and shows that studies are needed to determine the prevalence and incidence of rickettsioses in Mexico.

  3. High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers.

    PubMed

    Chew, G L; Huang, D; Lin, S J; Huo, C; Blick, T; Henderson, M A; Hill, P; Cawson, J; Morrison, W A; Campbell, I G; Hopper, J L; Southey, M C; Haviv, I; Thompson, E W

    2012-08-01

    Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

  4. 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

  5. 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

  6. SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis.

    PubMed

    Ginger, Rebecca S; Askew, Sarah E; Ogborne, Richard M; Wilson, Stephen; Ferdinando, Dudley; Dadd, Tony; Smith, Adrian M; Kazi, Shubana; Szerencsei, Robert T; Winkfein, Robert J; Schnetkamp, Paul P M; Green, Martin R

    2008-02-29

    A non-synonymous single nucleotide polymorphism in the human SLC24A5 gene is associated with natural human skin color variation. Multiple sequence alignments predict that this gene encodes a member of the potassium-dependent sodium-calcium exchanger family denoted NCKX5. In cultured human epidermal melanocytes we show using affinity-purified antisera that native human NCKX5 runs as a triplet of approximately 43 kDa on SDS-PAGE and is partially localized to the trans-Golgi network. Removal of the NCKX5 protein through small interfering RNA-mediated knockdown disrupts melanogenesis in human and murine melanocytes, causing a significant reduction in melanin pigment production. Using a heterologous expression system, we confirm for the first time that NCKX5 possesses the predicted exchanger activity. Site-directed mutagenesis of NCKX5 and NCKX2 in this system reveals that the non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue that is important for NCKX5 and NCKX2 activity. We suggest that NCKX5 directly regulates human epidermal melanogenesis and natural skin color through its intracellular potassium-dependent exchanger activity.

  7. 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

  8. 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.

  9. 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.

  10. 340 Facility maintenance implementation plan

    SciTech Connect

    1995-03-01

    This Maintenance Implementation Plan (MIP) has been developed for maintenance functions associated with the 340 Facility. This plan is developed from the guidelines presented by Department of Energy (DOE) Order 4330.4B, Maintenance Management Program (DOE 1994), Chapter II. The objective of this plan is to provide baseline information for establishing and identifying Westinghouse Hanford Company (WHC) conformance programs and policies applicable to implementation of DOE order 4330.4B guidelines. In addition, this maintenance plan identifies the actions necessary to develop a cost-effective and efficient maintenance program at the 340 Facility. Primary responsibility for the performance and oversight of maintenance activities at the 340 Facility resides with Westinghouse Hanford Company (WHC). Maintenance at the 340 Facility is performed by ICF-Kaiser Hanford (ICF-KH) South Programmatic Services crafts persons. This 340 Facility MIP provides interface requirements and responsibilities as they apply specifically to the 340 Facility. This document provides an implementation schedule which has been developed for items considered to be deficient or in need of improvement. The discussion sections, as applied to implementation at the 340 Facility, have been developed from a review of programs and practices utilizing the graded approach. Biennial review and additional reviews are conducted as significant programmatic and mission changes are made. This document is revised as necessary to maintain compliance with DOE requirements.

  11. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE... preventive maintenance, rebuilds, or alters an aircraft, airframe, aircraft engine, propeller, appliance, or... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in...

  12. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE... preventive maintenance, rebuilds, or alters an aircraft, airframe, aircraft engine, propeller, appliance, or... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in...

  13. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND... maintain, rebuild, alter, or perform preventive maintenance on an aircraft, airframe, aircraft engine... under part 61 may perform preventive maintenance on any aircraft owned or operated by that pilot which...

  14. Ryanodine receptors are expressed in epidermal keratinocytes and associated with keratinocyte differentiation and epidermal permeability barrier homeostasis.

    PubMed

    Denda, Sumiko; Kumamoto, Junichi; Takei, Kentaro; Tsutsumi, Moe; Aoki, Hirofumi; Denda, Mitsuhiro

    2012-01-01

    Ryanodine receptors (RyRs) have an important role as calcium channels in the regulation of intracellular calcium levels in the nervous system and muscle. In the present study, we investigated the expression of RyR in human epidermis. Immunohistochemical studies and reverse transcription-PCR indicated the expression of RyR type 1, 2, and 3 proteins in epidermal keratinocytes. The expression level of each RyR subtype was higher in differentiating keratinocytes than in proliferative cells. We also demonstrated the functional expression of RyR by calcium imaging. In cultured human keratinocytes, application of the RyR agonist 4-chloro-m-cresol (CMC) induced elevation of the intracellular calcium concentration, and co-application of the RyR antagonist 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP) blocked the elevation. Application of CMC accelerated keratinocyte differentiation in vitro. On the other hand, topical application of CMC after tape-stripping of hairless mouse skin delayed barrier recovery, whereas application of an RyR antagonist, dantrolene or DHBP, accelerated the barrier recovery. These results suggest that RyR expressed in epidermal keratinocytes is associated with both differentiation of keratinocytes and epidermal barrier homeostasis.

  15. The temporal and spatial expression of the novel Ca++-binding proteins, Scarf and Scarf2, during development and epidermal differentiation.

    PubMed

    Hwang, M; Kalinin, A; Morasso, M I

    2005-08-01

    During the process of epidermal differentiation, intracellular and extracellular calcium (Ca++) concentrations induce an array of signaling pathways . Keratinocytes follow a complex Ca++-dependent program of differentiation moving from the basal proliferative layer, through the spinous and granular differentiated layers to ultimately culminate in the formation of the cornified layer of the epidermis. Members of the Ca++-binding proteins play a central role in the transduction of Ca++ signals. Utilizing a suppressive subtractive hybridization screen comparing basal and differentiated keratinocytes, we identified the novel Ca++-binding protein genes, Scarf (skin Calmodulin-related factor) and Scarf2, which have homology to calmodulin (CaM). In this study, we present a comprehensive analysis of the expression pattern for Scarf and Scarf2 transcripts and proteins in the developing mouse. To examine Scarf2 expression during embryogenesis, we performed in situ hybridization, and detected expression in the hair follicle, skin and nasal epithelium. These results showed substantial overlap with the previously reported Scarf gene expression [Hwang, M., Morasso, M.I., 2003. The novel murine Ca2+-binding protein, Scarf, is differentially expressed during epidermal differentiation. J. Biol. Chem. 278, 47827-47833]. Comparing the expression patterns of Scarf and Scarf2 proteins in neonatal and adult mouse skin with several structural epidermal proteins, i.e. keratin 14 (K14), keratin 1 (K1), loricrin (LOR) and filaggrin (FIL) showed that their expression overlaps K1, an early marker of keratinocyte differentiation. Interestingly, Scarf and Scarf2 were also detected in the tongue and oral epithelia, rib bone undergoing ossification and in the medullar region of thymus.

  16. Utility of a topical peroxisome proliferator-activated receptor-α ligand with glucocorticoids in a hapten-induced murine model with features of atopic dermatitis

    PubMed Central

    Hatano, Yutaka; Elias, Peter M.; Crumrine, Debra; Feingold, Kenneth R.; Katagiri, Kazumoto; Fujiwara, Sakuhei

    2011-01-01

    Although topical glucocorticoids (GCs) display potent anti-inflammatory activity in inflamed skin, they also can exert numerous harmful effects on epidermal structure and function. In contrast, topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) not only reduce inflammation, and also improve cutaneous barrier homeostasis. Therefore, we examined whether sequential topical GCs followed by topical Wy14643 (a ligand of PPARα) might be more effective than either alone for atopic dermatitis (AD) in a hapten (oxazolone)-induced, murine model with multiple features of AD (Ox-AD). Despite expected anti-inflammatory benefits, topical GC alone induced: i) epidermal thinning; ii) reduced expression of involucrin, loricrin and filaggrin; and iii) allowed outside-to-inside penetration of an epicutaneous tracer. While Wy14643 alone yielded significant therapeutic benefits in mice with mild or moderate Ox-AD, it was less effective in severe Ox-AD. Yet, topical applications of Wy14643 after GC was not only significantly effective comparable to GC alone, but it also prevented GC-induced structural and functional abnormalities in permeability barrier homeostasis. Moreover, rebound flares were largely absent after sequential treatment with GC and Wy14643. Together, these results show that GC and PPARα ligand therapy together is not only effective but also prevents development of GC-induced side effects, including rebound flares, in murine AD. PMID:21633371

  17. Deferred School Maintenance Creates National Crises.

    ERIC Educational Resources Information Center

    Geiger, Philip E.

    2002-01-01

    Describes the cost and causes of the school maintenance "crises"; lists seven questions to determine if a school district has a quality maintenance program; describes consequences of deferred school maintenance in Yuma (Arizona) Union High School District. (PKP)

  18. 14 CFR 135.425 - Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.425 Maintenance, preventive maintenance, and alteration programs. Each certificate holder shall have an inspection program and... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Maintenance, preventive maintenance, and...

  19. 14 CFR 135.423 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.423 Maintenance, preventive maintenance, and alteration organization. (a) Each certificate holder that performs any of its... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Maintenance, preventive maintenance, and...

  20. 14 CFR 135.437 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.437 Authority to perform and approve maintenance, preventive maintenance, and alterations... maintenance, preventive maintenance, and alterations. 135.437 Section 135.437 Aeronautics and Space FEDERAL...

  1. 14 CFR 135.423 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.423 Maintenance, preventive maintenance, and alteration organization. (a) Each certificate holder that performs any of its... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Maintenance, preventive maintenance, and...

  2. 14 CFR 135.425 - Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.425 Maintenance, preventive maintenance, and alteration programs. Each certificate holder shall have an inspection program and... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Maintenance, preventive maintenance, and...

  3. 14 CFR 135.437 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.437 Authority to perform and approve maintenance, preventive maintenance, and alterations... maintenance, preventive maintenance, and alterations. 135.437 Section 135.437 Aeronautics and Space FEDERAL...

  4. 14 CFR 121.379 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... maintenance, preventive maintenance, and alterations. 121.379 Section 121.379 Aeronautics and Space FEDERAL... OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.379 Authority to perform and approve maintenance, preventive maintenance, and alterations. (a) A certificate holder may perform, or it may...

  5. 14 CFR 121.379 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... maintenance, preventive maintenance, and alterations. 121.379 Section 121.379 Aeronautics and Space FEDERAL... OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.379 Authority to perform and approve maintenance, preventive maintenance, and alterations. (a) A certificate holder may perform, or it may...

  6. 14 CFR 121.365 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Maintenance, preventive maintenance, and..., Preventive Maintenance, and Alterations § 121.365 Maintenance, preventive maintenance, and alteration...), preventive maintenance, or alterations, and each person with whom it arranges for the performance of...

  7. 14 CFR 135.437 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... maintenance, preventive maintenance, and alterations. 135.437 Section 135.437 Aeronautics and Space FEDERAL... AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.437 Authority to perform and approve maintenance, preventive maintenance, and...

  8. 14 CFR 135.423 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Maintenance, preventive maintenance, and... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.423 Maintenance, preventive maintenance, and alteration organization. (a) Each certificate holder that performs any of...

  9. 14 CFR 135.425 - Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Maintenance, preventive maintenance, and... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.425 Maintenance, preventive maintenance, and alteration programs. Each certificate holder shall have an inspection program...

  10. 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..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty time limitations. Within the United States, each certificate holder (or person performing maintenance or...

  11. 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..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty time limitations. Within the United States, each certificate holder (or person performing maintenance or...

  12. 14 CFR 135.437 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... maintenance, preventive maintenance, and alterations. 135.437 Section 135.437 Aeronautics and Space FEDERAL... AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.437 Authority to perform and approve maintenance, preventive maintenance, and...

  13. 14 CFR 121.375 - Maintenance and preventive maintenance training program.

    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... OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.375 Maintenance and preventive maintenance training program....

  14. 14 CFR 135.425 - Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Maintenance, preventive maintenance, and... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.425 Maintenance, preventive maintenance, and alteration programs. Each certificate holder shall have an inspection program...

  15. 14 CFR 121.379 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... maintenance, preventive maintenance, and alterations. 121.379 Section 121.379 Aeronautics and Space FEDERAL... OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.379 Authority to perform and approve maintenance, preventive maintenance, and alterations. (a) A certificate holder may perform, or it may...

  16. 14 CFR 135.437 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... maintenance, preventive maintenance, and alterations. 135.437 Section 135.437 Aeronautics and Space FEDERAL... AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.437 Authority to perform and approve maintenance, preventive maintenance, and...

  17. 14 CFR 121.375 - Maintenance and preventive maintenance training program.

    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... OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.375 Maintenance and preventive maintenance training program....

  18. 14 CFR 121.379 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... maintenance, preventive maintenance, and alterations. 121.379 Section 121.379 Aeronautics and Space FEDERAL... OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.379 Authority to perform and approve maintenance, preventive maintenance, and alterations. (a) A certificate holder may perform, or it may...

  19. 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..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty time limitations. Within the United States, each certificate holder (or person performing maintenance or...

  20. 14 CFR 121.365 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Maintenance, preventive maintenance, and..., Preventive Maintenance, and Alterations § 121.365 Maintenance, preventive maintenance, and alteration...), preventive maintenance, or alterations, and each person with whom it arranges for the performance of...

  1. 14 CFR 121.365 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Maintenance, preventive maintenance, and..., Preventive Maintenance, and Alterations § 121.365 Maintenance, preventive maintenance, and alteration...), preventive maintenance, or alterations, and each person with whom it arranges for the performance of...

  2. 14 CFR 121.375 - Maintenance and preventive maintenance training program.

    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... OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.375 Maintenance and preventive maintenance training program....

  3. 14 CFR 135.423 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Maintenance, preventive maintenance, and... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.423 Maintenance, preventive maintenance, and alteration organization. (a) Each certificate holder that performs any of...

  4. 14 CFR 121.379 - Authority to perform and approve maintenance, preventive maintenance, and alterations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... maintenance, preventive maintenance, and alterations. 121.379 Section 121.379 Aeronautics and Space FEDERAL... OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.379 Authority to perform and approve maintenance, preventive maintenance, and alterations. (a) A certificate holder may perform, or it may...

  5. 14 CFR 135.425 - Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Maintenance, preventive maintenance, and... ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.425 Maintenance, preventive maintenance, and alteration programs. Each certificate holder shall have an inspection program...

  6. 14 CFR 121.375 - Maintenance and preventive maintenance training program.

    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... OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.375 Maintenance and preventive maintenance training program....

  7. 14 CFR 121.365 - Maintenance, preventive maintenance, and alteration organization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Maintenance, preventive maintenance, and..., Preventive Maintenance, and Alterations § 121.365 Maintenance, preventive maintenance, and alteration...), preventive maintenance, or alterations, and each person with whom it arranges for the performance of...

  8. 14 CFR 121.375 - Maintenance and preventive maintenance training program.

    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... OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.375 Maintenance and preventive maintenance training program....

  9. 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..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty time limitations. Within the United States, each certificate holder (or person performing maintenance or...

  10. 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..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty time limitations. Within the United States, each certificate holder (or person performing maintenance or...

  11. 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

  12. 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)

  13. Endeavour Return to Flight Maintenance

    NASA Image and Video Library

    2003-10-10

    In the Orbiter Processing Facility, David Sanborn and Rick Cady, with United Space Alliance, check tiles on the underside of Endeavour. Tile check is part of routine maintenance and return to flight activities on the orbiter fleet.

  14. Contract Service for School Maintenance

    ERIC Educational Resources Information Center

    Modern Schools, 1976

    1976-01-01

    Preventive maintenance can extend useful equipment life in a school building and keep systems running more efficiently. Points to consider before selecting a comprehensive energy management package are listed. (Author/MLF)

  15. 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…

  16. 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)

  17. 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, ...

  18. The Magic of Lighting Maintenance

    ERIC Educational Resources Information Center

    Modern Schools, 1973

    1973-01-01

    A well-planned lighting maintenance program can provide more light for your money, better appearance of the lighting system, lower overall cost of light, and fewer accidents and better visibility for users of the school. (Author)

  19. 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.

  20. Genetic evidence that Shp-2 tyrosine phosphatase is a signal enhancer of the epidermal growth factor receptor in mammals

    PubMed Central

    Qu, Cheng-Kui; Yu, Wen-Mei; Azzarelli, Biagio; Feng, Gen-Sheng

    1999-01-01

    By using both genetic and biochemical approaches, we have investigated the physiological role of Shp-2, a cytoplasmic tyrosine phosphatase with two Src homology 2 domains, in signaling pathways downstream of epidermal growth factor receptor (EGF-R). In previous studies, a targeted deletion mutation in the SH2-N domain of Shp-2 was introduced into the murine Shp-2 locus, which resulted in embryonic lethality of homozygous mutant (Shp-2−/−) mice at midgestation. By aggregating Shp-2−/− embryonic stem cells with wild-type embryos, we created Shp-2−/−/wild-type chimeric animals. Most chimeras had open eyelids at birth and abnormal skin development, a phenotype characteristic of mice with mutations in EGF-R signaling components. In genetic crosses, a heterozygous Shp-2 mutation dominantly enhanced the phenotype of a weak mutant allele of EGF-R (wa-2), resulting in distinctive growth retardation, developmental defects in the skin, lung, and intestine, and perinatal mortality that are reminiscent of EGF-R knockout mice. Biochemical analysis revealed that signal propagation proximal to the EGF-R upon EGF stimulation was significantly attenuated in wa-2 fibroblast cells, which was exacerbated by the additional Shp-2 mutation. Thus, we provide biological evidence here that protein-tyrosine phosphatase Shp-2 acts to enhance information flow from the EGF-R in mouse growth and development. PMID:10411909