Sample records for occlusion regulates epidermal

  1. Angiopoietin-Like 4 Regulates Epidermal Differentiation

    PubMed Central

    Huang, Royston-Luke; Goh, Yan Yih; Wang, Xiao Ling; Tang, Mark Boon Yang; Tan, Nguan Soon

    2011-01-01

    The nuclear hormone receptor PPARβ/δ is integral to efficient wound re-epithelialization and implicated in epidermal maturation. However, the mechanism underlying the latter process of epidermal differentiation remains unclear. We showed that ligand-activated PPARβ/δ indirectly stimulated keratinocyte differentiation, requiring de novo gene transcription and protein translation. Using organotypic skin cultures constructed from PPARβ/δ- and angiopoietin-like 4 (ANGPTL4)-knockdown human keratinocytes, we showed that the expression of ANGPTL4, a PPARβ/δ target gene, is essential for the receptor mediated epidermal differentiation. The pro-differentiation effect of PPARβ/δ agonist GW501516 was also abolished when keratinocytes were co-treated with PPARβ/δ antagonist GSK0660 and similarly in organotypic skin culture incubated with blocking ANGPTL4 monoclonal antibody targeted against the C-terminal fibrinogen-like domain. Our focused real-time PCR gene expression analysis comparing the skin biopsies from wildtype and ANGPTL4-knockout mice confirmed a consistent down-regulation of numerous genes involved in epidermal differentiation and proliferation in the ANGPTL4-knockout skin. We further showed that the deficiency of ANGPTL4 in human keratinocytes and mice skin have diminished expression of various protein kinase C isotypes and phosphorylated transcriptional factor activator protein-1, which are well-established for their roles in keratinocyte differentiation. Chromatin immunoprecipitation confirmed that ANGPTL4 stimulated the activation and binding of JUNB and c-JUN to the promoter region of human involucrin and transglutaminase type 1 genes, respectively. Taken together, we showed that PPARβ/δ regulates epidermal maturation via ANGPTL4-mediated signalling pathway. PMID:21966511

  2. Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

    PubMed

    Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

    2018-03-27

    Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

  3. Identification of Candidate Transcriptional Regulators of Epidermal Transfer Cell Development in Vicia faba Cotyledons

    PubMed Central

    Arun-Chinnappa, Kiruba S.; McCurdy, David W.

    2016-01-01

    Transfer cells (TCs) are anatomically-specialized cells formed at apoplasmic-symplasmic bottlenecks in nutrient transport pathways in plants. TCs form invaginated wall ingrowths which provide a scaffold to amplify plasma membrane surface area and thus increase the density of nutrient transporters required to achieve enhanced nutrient flow across these bottlenecks. Despite their importance to nutrient transport in plants, little is known of the transcriptional regulation of wall ingrowth formation. Here, we used RNA-Seq to identify transcription factors putatively involved in regulating epidermal TC development in cotyledons of Vicia faba. Comparing cotyledons cultured for 0, 3, 9, and 24 h to induce trans-differentiation of epidermal TCs identified 43 transcription factors that showed either epidermal-specific or epidermal–enhanced expression, and 10 that showed epidermal-specific down regulation. Members of the WRKY and ethylene-responsive families were prominent in the cohort of transcription factors showing epidermal-specific or epidermal–enhanced expression, consistent with the initiation of TC development often representing a response to stress. Members of the MYB family were also prominent in these categories, including orthologs of MYB genes involved in localized secondary wall deposition in Arabidopsis thaliana. Among the group of transcription factors showing down regulation were various homeobox genes and members of the MADs-box and zinc-finger families of poorly defined functions. Collectively, this study identified several transcription factors showing expression characteristics and orthologous functions that indicate likely participation in transcriptional regulation of epidermal TC development in V. faba cotyledons. PMID:27252730

  4. 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

  5. Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation

    PubMed Central

    Cobzaru, Cristina; Triantafyllopoulou, Antigoni; Löffek, Stefanie; Horiuchi, Keisuke; Threadgill, David W.; Kurz, Thomas; van Rooijen, Nico; Bruckner-Tuderman, Leena

    2012-01-01

    ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17ΔKC) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17ΔKC skin, and topical treatment of A17ΔKC mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (EgfrΔKC) closely resembled A17ΔKC mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17–EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects. PMID:22565824

  6. 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.

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

    PubMed Central

    Bansal, Dhiru; Kulkarni, Jahnavi; Nadahalli, Kavana; Lakshmanan, Vairavan; Krishna, Srikar; Sasidharan, Vidyanand; Dilipkumar, Shilpa; Gulyani, Akash; Raghavan, Srikala

    2017-01-01

    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. PMID:28807897

  8. Caenorhabditis elegans anillin (ani-1) regulates neuroblast cytokinesis and epidermal morphogenesis during embryonic development.

    PubMed

    Fotopoulos, N; Wernike, D; Chen, Y; Makil, N; Marte, A; Piekny, A

    2013-11-01

    The formation of tissues is essential for metazoan development. During Caenorhabditis elegans embryogenesis, ventral epidermal cells migrate to encase the ventral surface of the embryo in a layer of epidermis by a process known as ventral enclosure. This process is regulated by guidance cues secreted by the underlying neuroblasts. However, since the cues and their receptors are differentially expressed in multiple cell types, the role of the neuroblasts in ventral enclosure is not fully understood. Furthermore, although F-actin is required for epidermal cell migration, it is not known if nonmuscle myosin is also required. Anillin (ANI-1) is an actin and myosin-binding protein that coordinates actin-myosin contractility in the early embryo. Here, we show that ANI-1 localizes to the cleavage furrows of dividing neuroblasts during mid-embryogenesis and is required for their division. Embryos depleted of ani-1 display a range of ventral enclosure phenotypes, where ventral epidermal cells migrate with similar speeds to control embryos, but contralateral neighbors often fail to meet and are misaligned. The ventral enclosure phenotypes in ani-1 RNAi embryos suggest that the position or shape of neuroblasts is important for directing ventral epidermal cell migration, although does not rule out an autonomous requirement for ani-1 in the epidermal cells. Furthermore, we show that rho-1 and other regulators of nonmuscle myosin activity are required for ventral epidermal cell migration. Interestingly, altering nonmuscle myosin contractility alleviates or strengthens ani-1's ventral enclosure phenotypes. Our findings suggest that ventral enclosure is a complex process that likely relies on inputs from multiple tissues. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Heppner, David E; van der Vliet, Albert

    2016-08-01

    Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs) that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR), a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Epidermal wound repair is regulated by the planar cell polarity signaling pathway.

    PubMed

    Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A; Murdoch, Jennifer N; Humbert, Patrick O; Parekh, Vishwas; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M; Jane, Stephen M

    2010-07-20

    The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3(-)(/-) mice, we identified RhoGEF19, a homolog of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerization, cellular polarity, and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling and broadly implicate this pathway in epidermal repair. (c) 2010 Elsevier Inc. All rights reserved.

  11. Epidermal wound repair is regulated by the planar cell polarity signaling pathway

    PubMed Central

    Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B.; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A.; Murdoch, Jennifer N.; Humbert, Patrick O.; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M.; Jane, Stephen M.

    2010-01-01

    SUMMARY The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3−/− mice, we identified RhoGEF19, a homologue of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerisation, cellular polarity and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling, and broadly implicate this pathway in epidermal repair. PMID:20643356

  12. Epidermal regulation of dermal fibroblast activity.

    PubMed

    Garner, W L

    1998-07-01

    Although the association between delayed burn wound healing and subsequent hypertrophic scar formation is well-established, the mechanism for this relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a possible regulatory role for the epidermis in controlling dermal fibroblast matrix synthesis. Therefore, we examined the effect of epidermal cells and media conditioned by epidermal cells on fibroblast collagen synthesis and replication. Purified fibroblast and keratinocyte cell strains were developed from discarded normal adult human skin. Conditioned media were created by incubation of cytokine-free and serum-free medium with either confluent fibroblast or keratinocyte cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed for 48 hours to graded concentrations of either unconditioned medium (control), conditioned medium, or varying numbers of keratinocytes. Replication was quantified by the incorporation of 3H-thymidine. Collagen synthesis was measured by the incorporation of 3H-proline into collagenase-sensitive protein. Data were compared using analysis of variance (ANOVA) and linear regression. Keratinocyte conditioned medium induced a significant increase in replication (n = 3) (p = 0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast, neither fibroblast conditioned medium nor control medium had an effect on fibroblast replication or collagen synthesis. Co-culture of fibroblast with a graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p < 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a soluble keratinocyte product. This result suggests a mechanism for the clinical observation that unhealed burn wounds, which lack the epidermis, demonstrate excess collagen production and scar. Clinical strategies to decrease hypertrophic scar should include an attempt at early wound closure with skin grafting or the application of cultured epithelial

  13. [Progress in epidermal stem cells].

    PubMed

    Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

    2010-03-01

    Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

  14. TORNADO1 regulates root epidermal patterning through the WEREWOLF pathway in Arabidopsis thaliana.

    PubMed

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-01-01

    Cell fate in the root epidermis of Arabidopsis thaliana is determined in a position-dependent manner. SCRAMBLED (SCM), an atypical leucine-rich repeat receptor-like kinase, mediates this positional regulation via its effect on WEREWOLF (WER) expression, and subsequently, its downstream transcription factor, GLABRA2 (GL2), which are required for nonhair cell development. Previously, TORNADO1 (TRN1), a plant-specific protein with a leucine-rich repeat ribonuclease inhibitor-like domain, was shown to be required for proper epidermal patterning in Arabidopsis roots. In this work, we analyzed the possible involvement of TRN1 in the known root epidermal gene network. We discovered that the trn1 mutant caused the ectopic expression of WER and the randomized expression of GL2 and EGL3. This suggests that TRN1 regulates the position-dependent cell fate determination by affecting WER expression in Arabidopsis root epidermis. Additionally, the distinct phenotypes of the aerial parts of the trn1-t and scm-2 mutant suggest that TRN1 and SCM might have different functions in the development of aerial parts.

  15. TORNADO1 regulates root epidermal patterning through the WEREWOLF pathway in Arabidopsis thaliana

    PubMed Central

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-01-01

    Cell fate in the root epidermis of Arabidopsis thaliana is determined in a position-dependent manner. SCRAMBLED (SCM), an atypical leucine-rich repeat receptor-like kinase, mediates this positional regulation via its effect on WEREWOLF (WER) expression, and subsequently, its downstream transcription factor, GLABRA2 (GL2), which are required for nonhair cell development. Previously, TORNADO1 (TRN1), a plant-specific protein with a leucine-rich repeat ribonuclease inhibitor-like domain, was shown to be required for proper epidermal patterning in Arabidopsis roots. In this work, we analyzed the possible involvement of TRN1 in the known root epidermal gene network. We discovered that the trn1 mutant caused the ectopic expression of WER and the randomized expression of GL2 and EGL3. This suggests that TRN1 regulates the position-dependent cell fate determination by affecting WER expression in Arabidopsis root epidermis. Additionally, the distinct phenotypes of the aerial parts of the trn1-t and scm-2 mutant suggest that TRN1 and SCM might have different functions in the development of aerial parts. PMID:26451798

  16. Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

    PubMed Central

    Wurm, Stefanie; Zhang, Jisheng; Guinea-Viniegra, Juan; García, Fernando; Muñoz, Javier; Bakiri, Latifa; Ezhkova, Elena

    2015-01-01

    Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation. PMID:25547114

  17. 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

  18. Mast Cells Regulate Epidermal Barrier Function and the Development of Allergic Skin Inflammation.

    PubMed

    Sehra, Sarita; Serezani, Ana P M; Ocaña, Jesus A; Travers, Jeffrey B; Kaplan, Mark H

    2016-07-01

    Atopic dermatitis is a chronic inflammatory skin disease characterized by infiltration of eosinophils, T helper cells, and mast cells. The role of mast cells in atopic dermatitis is not completely understood. To define the effects of mast cells on skin biology, we observed that mast cells regulate the homeostatic expression of epidermal differentiation complex and other skin genes. Decreased epidermal differentiation complex gene expression in mice that genetically lack mast cells (Kit(W-sh/W-sh) mice) is associated with increased uptake of protein antigens painted on the skin by dendritic cells (DCs) compared with similarly treated wild-type mice, suggesting a protective role for mast cells in exposure to nominal environmental allergens. To test this further, we crossed Kit(W-sh/W-sh) mice with signal transducer and activator of transcription 6 (i.e., Stat6) VT transgenic mice that develop spontaneous atopic dermatitis-like disease that is dependent on T helper cell 2 cytokines and is associated with high serum concentrations of IgE. We observed that Stat6VT × Kit(W-sh/W-sh) mice developed more frequent and more severe allergic skin inflammation than Stat6VT transgenic mice that had mast cells. Together, these studies suggest that mast cells regulate epidermal barrier function and have a potential protective role in the development of atopic dermatitis-like disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Yorkie regulates epidermal wound healing in Drosophila larvae independently of cell proliferation and apoptosis.

    PubMed

    Tsai, Chang-Ru; Anderson, Aimee E; Burra, Sirisha; Jo, Juyeon; Galko, Michael J

    2017-07-01

    Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki transiently translocates to some epidermal nuclei upon wounding. Genetic analysis strongly suggests that Yki interacts with the known wound healing pathway, Jun N-terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular-Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or parallel to JNK signaling and does not appear to regulate either proliferation or apoptosis in the larval epidermis during wound repair. Analysis of actin structures after wounding suggests that Yki and Sd promote wound closure through actin regulation. In sum, we found that Yki regulates an epithelial tissue repair process independently of its previously documented roles in balancing proliferation and apoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Notch Signaling Regulates Late-Stage Epidermal Differentiation and Maintains Postnatal Hair Cycle Homeostasis

    PubMed Central

    Lin, Hsien-Yi; Kao, Cheng-Heng; Lin, Kurt Ming-Chao; Kaartinen, Vesa; Yang, Liang-Tung

    2011-01-01

    Background Notch signaling involves ligand-receptor interactions through direct cell-cell contact. Multiple Notch receptors and ligands are expressed in the epidermis and hair follicles during embryonic development and the adult stage. Although Notch signaling plays an important role in regulating differentiation of the epidermis and hair follicles, it remains unclear how Notch signaling participates in late-stage epidermal differentiation and postnatal hair cycle homeostasis. Methodology and Principal Findings We applied Cre/loxP system to generate conditional gene targeted mice that allow inactivation of critical components of Notch signaling pathway in the skin. Rbpj, the core component of all four Notch receptors, and Pofut1, an essential factor for ligand-receptor interactions, were inactivated in hair follicle lineages and suprabasal layer of the epidermis using the Tgfb3-Cre mouse line. Rbpj conditional inactivation resulted in granular parakeratosis and reactive epidermal hyperplasia. Pofut1 conditional inactivation led to ultrastructural abnormalities in the granular layer and altered filaggrin processing in the epidermis, suggesting a perturbation of the granular layer differentiation. Disruption of Pofut1 in hair follicle lineages resulted in aberrant telogen morphology, a decrease of bulge stem cell markers, and a concomitant increase of K14-positive keratinocytes in the isthmus of mutant hair follicles. Pofut1-deficent hair follicles displayed a delay in anagen re-entry and dysregulation of proliferation and apoptosis during the hair cycle transition. Moreover, increased DNA double stand breaks were detected in Pofut1-deficent hair follicles, and real time PCR analyses on bulge keratinocytes isolated by FACS revealed an induction of DNA damage response and a paucity of DNA repair machinery in mutant bulge keratinocytes. Significance our data reveal a role for Notch signaling in regulating late-stage epidermal differentiation. Notch signaling is

  1. iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function

    PubMed Central

    Brooke, Matthew A.; Etheridge, Sarah L.; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A.; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P.

    2014-01-01

    iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. PMID:24643277

  2. Epidermal stem cells: location, potential and contribution to cancer.

    PubMed

    Ambler, C A; Määttä, A

    2009-01-01

    Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

  3. iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.

    PubMed

    Brooke, Matthew A; Etheridge, Sarah L; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P

    2014-08-01

    iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. WEREWOLF, a MYB-related protein in Arabidopsis, is a position-dependent regulator of epidermal cell patterning.

    PubMed

    Lee, M M; Schiefelbein, J

    1999-11-24

    The formation of the root epidermis of Arabidopsis provides a simple and elegant model for the analysis of cell patterning. A novel gene, WEREWOLF (WER), is described here that is required for position-dependent patterning of the epidermal cell types. The WER gene encodes a MYB-type protein and is preferentially expressed within cells destined to adopt the non-hair fate. Furthermore, WER is shown to regulate the position-dependent expression of the GLABRA2 homeobox gene, to interact with a bHLH protein, and to act in opposition to the CAPRICE MYB. These results suggest a simple model to explain the specification of the two root epidermal cell types, and they provide insight into the molecular mechanisms used to control cell patterning.

  5. p63 Adjusts Sugar Taste of Epidermal Layers.

    PubMed

    Amelio, Ivano; Melino, Gerry; Candi, Eleonora

    2017-06-01

    p63 is a master regulator of epidermal biology, sustaining stemness and renewal capacity of the proliferating keratinocyte compartment. Hamanaka and Mutlu propose that p63 regulates the keratinocyte proliferation/differentiation switch by affecting the cellular glycolic rate through a direct transcriptional regulation of the metabolic enzyme PFKFB3. This finding sheds light on mechanisms underlining p63 function in the skin and suggests a role for energetic metabolism in epidermal biology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

    PubMed

    Casey, F P; Baird, D; Feng, Q; Gutenkunst, R N; Waterfall, J J; Myers, C R; Brown, K S; Cerione, R A; Sethna, J P

    2007-05-01

    We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

  7. Epidermal Notch signalling: differentiation, cancer and adhesion.

    PubMed

    Watt, Fiona M; Estrach, Soline; Ambler, Carrie A

    2008-04-01

    The Notch pathway plays an important role in regulating epidermal differentiation. Notch ligands, receptors and effectors are expressed in a complex and dynamic pattern in embryonic and adult skin. Genetic ablation or activation of the pathway reveals that Notch signalling promotes differentiation of the hair follicle, sebaceous gland and interfollicular epidermal lineages and that Notch acts as an epidermal tumour suppressor. Notch signalling interacts with a range of other pathways to fulfil these functions and acts via RBP-Jkappa dependent and independent mechanisms. The effects on differentiation can be cell autonomous and non-autonomous, and Notch contributes to stem cell clustering via modulation of cell adhesion.

  8. Developmental regulation by cytokines of bone marrow-derived dendritic cells and epidermal Langerhans cells.

    PubMed

    Yamaguchi, Y

    1998-01-01

    Dendritic cells (DC) are specialized antigen-presenting cells involved in T cell-mediated immune responses. Differentiation and functional maturation of the DC are now known to be regulated by various cytokines, including TGF-beta1. The experiments of this study examined the effect of other cytokines, such as IL-4, IL-10 and IL-6, on the differentiation and maturation of bone marrow (BM)-derived DC (BM-DC) and epidermal Langerhans cells (LC). When IL-6 or IL-10 was added to cultures of BM cells in the presence of GM-CSF, both cytokines, as in the case of TGF-beta1, suppressed the maturation of DC in terms of the expression of adhesion and costimulatory molecules and T cell-stimulating activity. In contrast, IL-4 was not suppressive but rather supportive for the differentiation of DC. However, these suppressive cytokines hardly counteracted the maturation-inducing activity of TNF-alpha when added to cultures of immature DC. In addition, they appeared to block the overmaturation of DC, which is characterized by a loss of MHC class II molecules. Regarding LC maturation in epidermal cell cultures, IL-6 and IL-10 were inhibitory for the expression of CD86 and CD80 in a dose-dependent fashion. Unlike BM-DC, LC maturation was slightly enhanced by TGF-beta1. The protein antigen-presentation by LC to Th1 clone was not affected by IL-6, but slightly reduced by IL-10. These results suggest that each cytokine contributes to regulate the differentiation and maturation of DC at a different developmental stage.

  9. Amputee skin condition: occlusion, stratum corneum hydration and free amino acid levels.

    PubMed

    Visscher, Marty O; Robinson, Marisa; Fugit, Benetta; Rosenberg, Richard J; Hoath, Steven B; Randall Wickett, R

    2011-03-01

    Patients with a prosthetic limb report negative skin effects, including irritation, rash and chafing, which can lead to infection, discomfort and reduced wear time to significantly impact normal activities. The aims were to examine the epidermal integrity (transepidermal water loss, TEWL), stratum corneum (SC) hydration [moisture accumulation rate (MAT)], friction and biomechanical properties in active below the knee amputees and to determine the effects of an inert sock liner on skin condition. The liner reduced hydration, TEWL and friction and increased elasticity versus the amputee's conventional skin care methods. Residual limb TEWL was increased and MAT was reduced versus the contralateral normal skin. In a second study, we hypothesized that complete occlusion would decrease free amino acids (FAA) and quantified them by high performance liquid chromatography in an adult volar forearm model. Occlusion with a water vapor impermeable wet dressing led to increased TEWL, erythema and dryness and reduced MAT versus normal skin, comparable to the results in the amputees. The FAA levels were significantly reduced for the occluded sites. The results suggest that residual limb occlusion in amputees may block the formation of FAA in the upper SC. Therapies based on replacement of water binding FAAs, may alleviate the consequences of long-term occlusion.

  10. JACKDAW controls epidermal patterning in the Arabidopsis root meristem through a non-cell-autonomous mechanism.

    PubMed

    Hassan, Hala; Scheres, Ben; Blilou, Ikram

    2010-05-01

    In Arabidopsis, specification of the hair and non-hair epidermal cell types is position dependent, in that hair cells arise over clefts in the underlying cortical cell layer. Epidermal patterning is determined by a network of transcriptional regulators that respond to an as yet unknown cue from underlying tissues. Previously, we showed that JACKDAW (JKD), a zinc finger protein, localizes in the quiescent centre and the ground tissue, and regulates tissue boundaries and asymmetric cell division by delimiting SHORT-ROOT movement. Here, we provide evidence that JKD controls position-dependent signals that regulate epidermal-cell-type patterning. JKD is required for appropriately patterned expression of the epidermal cell fate regulators GLABRA2, CAPRICE and WEREWOLF. Genetic interaction studies indicate that JKD operates upstream of the epidermal patterning network in a SCRAMBLED (SCM)-dependent fashion after embryogenesis, but acts independent of SCM in embryogenesis. Tissue-specific induction experiments indicate non-cell-autonomous action of JKD from the underlying cortex cell layer to specify epidermal cell fate. Our findings are consistent with a model where JKD induces a signal in every cortex cell that is more abundant in the hair cell position owing to the larger surface contact of cells located over a cleft.

  11. Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea.

    PubMed

    Cheng, Li-Chun; Tu, Kimberly C; Seidel, Chris W; Robb, Sofia M C; Guo, Fengli; Sánchez Alvarado, Alejandro

    2018-01-15

    The epidermis is essential for animal survival, providing both a protective barrier and cellular sensor to external environments. The generally conserved embryonic origin of the epidermis, but the broad morphological and functional diversity of this organ across animals is puzzling. We define the transcriptional regulators underlying epidermal lineage differentiation in the planarian Schmidtea mediterranea, an invertebrate organism that, unlike fruitflies and nematodes, continuously replaces its epidermal cells. We find that Smed-p53, Sox and Pax transcription factors are essential regulators of epidermal homeostasis, and act cooperatively to regulate genes associated with early epidermal precursor cell differentiation, including a tandemly arrayed novel gene family (prog) of secreted proteins. Additionally, we report on the discovery of distinct and previously undescribed secreted organelles whose production is dependent on the transcriptional activity of soxP-3, and which we term Hyman vesicles. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Resveratrol-Enriched Rice Down-Regulates Melanin Synthesis in UVB-Induced Guinea Pigs Epidermal Skin Tissue

    PubMed Central

    Lee, Taek Hwan; Seo, Jae Ok; Do, Moon Ho; Ji, Eunhee; Baek, So-Hyeon; Kim, Sun Yeou

    2014-01-01

    Synthetic compounds that are used in the clinic to regulate skin hyperpigmentation, such as arbutin, hydroquinone, and kojic acid, are only moderately effective. But, their use is limited by side effects. As part of an effort to overcome the limitations, we developed resveratrol-enriched rice (RR) using genetic engineering technique. Each of resveratrol and rice has been reported to produce anti-melanogenic effects. Therefore, we hypothesized that RR would show more anti-melanogenic effects than those of resveratrol or rice alone. Anti-melanogenic effect of RR was done by using melan-a mouse melanocytes. The depigmenting efficacy was then observed following topical application of the RR to UVB-stimulated hyperpigmented dorsal skin of guinea pigs. Treatment with RR extract resulted a 21.4 ± 0.7% decrease in tyrosinase expression at melan-a cells. Colorimetric analysis showed a significantly lower depigmenting value by day 9 following treatment with RR in UVB-irradiated guinea pigs the dorsal skin (p<0.01), indicating that RR produced a depigmentation effect. By staining with Fontana-Masson stain, we found that the RR-treated group had more effect histopathologically in epidermal melanin production than resveratrol or rice alone-treated group. RR was associated with reduction in the levels of microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase and tyrosinase-related protein (TRP-2) expression, leading to inhibit epidermal melanin production by western blot analysis. This study suggests that the resveratrol-enriched rice may be a promising candidate in regulating skin pigmentation with UVB exposure. PMID:25414774

  13. Epidermal Cell Death in Rice Is Regulated by Ethylene, Gibberellin, and Abscisic Acid

    PubMed Central

    Steffens, Bianka; Sauter, Margret

    2005-01-01

    Programmed cell death (PCD) of epidermal cells that cover adventitious root primordia in deepwater rice (Oryza sativa) is induced by submergence. Early suicide of epidermal cells may prevent injury to the growing root that emerges under flooding conditions. Induction of PCD is dependent on ethylene signaling and is further promoted by gibberellin (GA). Ethylene and GA act in a synergistic manner, indicating converging signaling pathways. Treatment of plants with GA alone did not promote PCD. Treatment with the GA biosynthesis inhibitor paclobutrazol resulted in increased PCD in response to ethylene and GA presumably due to an increased sensitivity of epidermal cells to GA. Abscisic acid (ABA) was shown to efficiently delay ethylene-induced as well as GA-promoted cell death. The results point to ethylene signaling as a target of ABA inhibition of PCD. Accumulation of ethylene and GA and a decreased ABA level in the rice internode thus favor induction of epidermal cell death and ensure that PCD is initiated as an early response that precedes adventitious root growth. PMID:16169967

  14. Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

    PubMed Central

    Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E.; Dagnino, Lina

    2012-01-01

    Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216

  15. Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

    PubMed

    Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

    2012-01-01

    Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

  16. [Relationship between Occlusal Discomfort Syndrome and Occlusal Threshold].

    PubMed

    Munakata, Motohiro; Ono, Yumie; Hayama, Rika; Kataoka, Kanako; Ikuta, Ryuhei; Tamaki, Katsushi

    2016-03-01

    Occlusal dysesthesia has been defined as persistent uncomfortable feelings of intercuspal position continuing for more than 6 months without evidence of physical occlusal discrepancy. The problem often occurs after occlusal intervention by dental care. Although various dental treatments (e. g. occlusal adjustment, orthodontic treatment and prosthetic reconstruction) are attempted to solve occlusal dysesthesia, they rarely reach a satisfactory result, neither for patients nor dentists. In Japan, these symptoms are defined by the term "Occlusal discomfort syndrome" (ODS). The aim of this study was to investigate the characteristics of ODS with the simple occlusal sensory perceptive and discriminative test. Twenty-one female dental patients with ODS (mean age 55.8 ± 19.2 years) and 21 age- and gender-matched dental patients without ODS (mean age 53.1 ± 16.8 years) participated in the study. Upon grinding occlusal registration foils that were stacked to different thicknesses, participants reported the thicknesses at which they recognized the foils (recognition threshold) and felt discomfort (discomfort threshold). Although there was no significant difference in occlusal recognition thresholds between the two patient groups, the discomfort threshold was significantly smaller in the patients with ODS than in those without ODS. Moreover, the recognition threshold showed an age-dependent increase in patients without ODS, whereas it remained comparable between the younger (< 60 years old) and elderly (60 years old or more) patient subgroups with ODS. These results suggest that occlusal discomfort threshold rather than recognition threshold is an issue in ODS. The foil grinding procedure is a simple and useful method to evaluate occlusal perceptive and discriminative abilities in patients with ODS.

  17. Planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

    PubMed Central

    Dworkin, Sebastian; Jane, Stephen M

    2011-01-01

    The planar cell polarity (PCP) pathway plays a critical role in diverse developmental processes that require coordinated cellular movement, including neural tube closure and renal tubulogenesis. Recent studies have demonstrated that this pathway also has emerging relevance to the epidermis, as PCP signaling underpins many aspects of skin biology and pathology, including epidermal development, hair orientation, stem cell division and cancer. Coordinated cellular movement required for epidermal repair in mammals is also regulated by PCP signaling, and in this context, a new PCP gene encoding the developmental transcription factor Grainyhead-like 3 (Grhl3) is critical. This review focuses on the role that PCP signaling plays in the skin across a variety of epidermal functions and highlights perturbations that induce epidermal pathologies. PMID:22041517

  18. Regulators of floral fragrance production and their target genes in petunia are not exclusively active in the epidermal cells of petals.

    PubMed

    Van Moerkercke, Alex; Galván-Ampudia, Carlos S; Verdonk, Julian C; Haring, Michel A; Schuurink, Robert C

    2012-05-01

    In which cells of the flower volatile biosynthesis takes place is unclear. In rose and snapdragon, some enzymes of the volatile phenylpropanoid/benzenoid pathway have been shown to be present in the epidermal cells of petals. It is therefore generally believed that the production of these compounds occurs in these cells. However, whether the entire pathway is active in these cells and whether it is exclusively active in these cells remains to be proven. Cell-specific transcription factors activating these genes will determine in which cells they are expressed. In petunia, the transcription factor EMISSION OF BENZENOIDS II (EOBII) activates the ODORANT1 (ODO1) promoter and the promoter of the biosynthetic gene isoeugenol synthase (IGS). The regulator ODO1 in turn activates the promoter of the shikimate gene 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Here the identification of a new target gene of ODO1, encoding an ABC transporter localized on the plasma membrane, PhABCG1, which is co-expressed with ODO1, is described. PhABCG1 expression is up-regulated in petals overexpressing ODO1 through activation of the PhABCG1 promoter. Interestingly, the ODO1, PhABCG1, and IGS promoters were active in petunia protoplasts originating from both epidermal and mesophyll cell layers of the petal, suggesting that the volatile phenylpropanoid/benzenoid pathway in petunia is active in these different cell types. Since volatile release occurs from epidermal cells, trafficking of (volatile) compounds between cell layers must be involved, but the exact function of PhABCG1 remains to be resolved.

  19. Regulators of floral fragrance production and their target genes in petunia are not exclusively active in the epidermal cells of petals

    PubMed Central

    Van Moerkercke, Alex; Galván-Ampudia, Carlos S.; Verdonk, Julian C.; Haring, Michel A.; Schuurink, Robert C.

    2012-01-01

    In which cells of the flower volatile biosynthesis takes place is unclear. In rose and snapdragon, some enzymes of the volatile phenylpropanoid/benzenoid pathway have been shown to be present in the epidermal cells of petals. It is therefore generally believed that the production of these compounds occurs in these cells. However, whether the entire pathway is active in these cells and whether it is exclusively active in these cells remains to be proven. Cell-specific transcription factors activating these genes will determine in which cells they are expressed. In petunia, the transcription factor EMISSION OF BENZENOIDS II (EOBII) activates the ODORANT1 (ODO1) promoter and the promoter of the biosynthetic gene isoeugenol synthase (IGS). The regulator ODO1 in turn activates the promoter of the shikimate gene 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Here the identification of a new target gene of ODO1, encoding an ABC transporter localized on the plasma membrane, PhABCG1, which is co-expressed with ODO1, is described. PhABCG1 expression is up-regulated in petals overexpressing ODO1 through activation of the PhABCG1 promoter. Interestingly, the ODO1, PhABCG1, and IGS promoters were active in petunia protoplasts originating from both epidermal and mesophyll cell layers of the petal, suggesting that the volatile phenylpropanoid/benzenoid pathway in petunia is active in these different cell types. Since volatile release occurs from epidermal cells, trafficking of (volatile) compounds between cell layers must be involved, but the exact function of PhABCG1 remains to be resolved. PMID:22345641

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

  1. Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors.

    PubMed Central

    Xiao, J H; Feng, X; Di, W; Peng, Z H; Li, L A; Chambon, P; Voorhees, J J

    1999-01-01

    The role of retinoic acid receptors (RARs) in intercellular regulation of cell growth was assessed by targeting a dominant-negative RARalpha mutant (dnRARalpha) to differentiated suprabasal cells of mouse epidermis. dnRARalpha lacks transcriptional activation but not DNA-binding and receptor dimerization functions. Analysis of transgenic mice revealed that dnRARalpha dose-dependently impaired induction of basal cell proliferation and epidermal hyperplasia by all-trans RA (tRA). dnRARalpha formed heterodimers with endogenous retinoid X receptor-alpha (RXRalpha) over RA response elements in competition with remaining endogenous RARgamma-RXRalpha heterodimers, and dose-dependently impaired retinoid-dependent gene transcription. To identify genes regulated by retinoid receptors and involved in cell growth control, we analyzed the retinoid effects on expression of the epidermal growth factor (EGF) receptor, EGF, transforming growth factor-alpha, heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin genes. In normal epidermis, tRA rapidly and selectively induced expression of HB-EGF but not the others. This induction occurred exclusively in suprabasal cells. In transgenic epidermis, dnRARalpha dose-dependently inhibited tRA induction of suprabasal HB-EGF and subsequent basal cell hyperproliferation. Together, our observations suggest that retinoid receptor heterodimers located in differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in turn stimulates basal cell growth via intercellular signaling. These events may underlie retinoid action in epidermal regeneration during wound healing. PMID:10075925

  2. Developmental patterning of the sub-epidermal integument cell layer in Arabidopsis seeds

    PubMed Central

    Coen, Olivier; Fiume, Elisa; Xu, Wenjia; De Vos, Delphine; Lu, Jing; Pechoux, Christine; Lepiniec, Loïc

    2017-01-01

    Angiosperm seed development is a paradigm of tissue cross-talk. Proper seed formation requires spatial and temporal coordination of the fertilization products – embryo and endosperm – and the surrounding seed coat maternal tissue. In early Arabidopsis seed development, all seed integuments were thought to respond homogenously to endosperm growth. Here, we show that the sub-epidermal integument cell layer has a unique developmental program. We characterized the cell patterning of the sub-epidermal integument cell layer, which initiates a previously uncharacterized extra cell layer, and identified TRANSPARENT TESTA 16 and SEEDSTICK MADS box transcription factors as master regulators of its polar development and cell architecture. Our data indicate that the differentiation of the sub-epidermal integument cell layer is insensitive to endosperm growth alone and to the repressive mechanism established by FERTILIZATION INDEPENDENT ENDOSPERM and MULTICOPY SUPPRESSOR OF IRA1 Polycomb group proteins. This work demonstrates the different responses of epidermal and sub-epidermal integument cell layers to fertilization. PMID:28348169

  3. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    PubMed

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  4. Epidermal Expression and Regulation of Interleukin-33 during Homeostasis and Inflammation: Strong Species Differences.

    PubMed

    Sundnes, Olav; Pietka, Wojciech; Loos, Tamara; Sponheim, Jon; Rankin, Andrew L; Pflanz, Stefan; Bertelsen, Vibeke; Sitek, Jan C; Hol, Johanna; Haraldsen, Guttorm; Khnykin, Denis

    2015-07-01

    IL-33 is a novel IL-1 family member with a putative role in inflammatory skin disorders and a complex biology. Therefore, recent conflicting data regarding its function in experimental models justify a close assessment of its tissue expression and regulation. Indeed, we report here that there are strong species differences in the expression and regulation of epidermal IL-33. In murine epidermis, IL-33 behaved similar to an alarmin, being constitutively expressed in keratinocyte nuclei and rapidly lost during acute inflammation. By contrast, human and porcine IL-33 were weakly expressed or absent in keratinocytes of noninflamed skin but induced during acute inflammation. To this end, we observed that expression of IL-33 in human keratinocytes but not murine keratinocytes was strongly induced by IFN-γ, and this upregulation completely depended on the presence of EGFR ligands. Accordingly, IFN-γ increased the expression of IL-33 in the basal layers of the epidermis in human ex vivo skin cultures only, despite good evidence of IFN-γ activity in cultures from both species. Together these findings demonstrate that a full understanding of IL-33 function in clinical settings must take species-specific differences into account.

  5. Embryonic control of epidermal cell patterning in the root and hypocotyl of Arabidopsis.

    PubMed

    Lin, Y; Schiefelbein, J

    2001-10-01

    A position-dependent pattern of epidermal cell types is produced during the development of the Arabidopsis seedling root and hypocotyl. To understand the origin and regulation of this patterning mechanism, we have examined the embryonic expression of the GLABRA2 (GL2) gene, which encodes a cell-type-specific transcription factor. Using in situ RNA hybridization and a sensitive GL2::GFP reporter, we discovered that a position-dependent pattern of GL2 expression is established within protodermal cells at the heart stage and is maintained throughout the remainder of embryogenesis. In addition, we show that an exceptional GL2 expression character and epidermal cell pattern arises during development of the root-hypocotyl junction, which represents an anatomical transition zone. Furthermore, we find that two of the genes regulating seedling epidermal patterning, TRANSPARENT TESTA GLABRA (TTG) and WEREWOLF (WER), also control the embryonic GL2 pattern, whereas the CAPRICE (CPC) and GL2 genes are not required to establish this pattern. These results indicate that position-dependent patterning of epidermal cell types begins at an early stage of embryogenesis, before formation of the apical meristems and shortly after the cellular anatomy of the protoderm and outer ground tissue layer is established. Thus, epidermal cell specification in the Arabidopsis seedling relies on the embryonic establishment of a patterning mechanism that is perpetuated postembryonically.

  6. Glucose transporter member 1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation in epidermal keratinocytes.

    PubMed

    Tochio, Takumi; Tanaka, Hiroshi; Nakata, Satoru

    2013-03-01

    Glucose transporter member 1 (GLUT-1) is one of the major facilitated glucose transporters and contributes to the promotion of keratinocyte proliferation in psoriasis and carcinogenic lesions. In this study, we postulate that GLUT-1 is involved in ultraviolet B (UVB)-induced epidermal hyperplasia. The purpose of this study is to investigate the possible role of GLUT-1 in UVB-induced hyperplasia. The effects of UVB on GLUT-1 expression levels were investigated in in vitro and in vivo studies. In addition, the involvement of epidermal growth factor (EGF) and hypoxia inducible factor-1 alpha (HIF-1α), transcriptional factors for GLUT-1, in GLUT-1-related events were investigated. GLUT-1 mRNA and its protein levels were markedly increased by UVB irradiation in HaCaT cells. In in vivo studies, a strong immunofluorescence signal of GLUT-1 was clearly observed around the basal layer of the epidermis, which proliferated excessively by UVB irradiation. In HaCaT cells, EGF mRNA and its protein levels were markedly increased by UVB irradiation, and then the GLUT-1 mRNA level was significantly increased by treatment with EGF. Additionally, the upregulation of GLUT-1 by both UVB irradiation and treatment with EGF was significantly suppressed by transfection with HIF-1α siRNA. We conclude that GLUT-1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation of epidermal basal cells, and the GLUT-1-related event might be regulated by an increase in HIF-1α stimulated by EGF. © 2013 The International Society of Dermatology.

  7. GLABROUS INFLORESCENCE STEMS modulates the regulation by gibberellins of epidermal differentiation and shoot maturation in Arabidopsis.

    PubMed

    Gan, Yinbo; Kumimoto, Rod; Liu, Chang; Ratcliffe, Oliver; Yu, Hao; Broun, Pierre

    2006-06-01

    As a plant shoot matures, it transitions through a series of growth phases in which successive aerial organs undergo distinct developmental changes. This process of phase change is known to be influenced by gibberellins (GAs). We report the identification of a putative transcription factor, GLABROUS INFLORESCENCE STEMS (GIS), which regulates aspects of shoot maturation in Arabidopsis thaliana. GIS loss-of-function mutations affect the epidermal differentiation of inflorescence organs, causing a premature decrease in trichome production on successive leaves, stem internodes, and branches. Overexpression has the opposite effect on trichome initiation and causes other heterochronic phenotypes, affecting flowering and juvenile-adult leaf transition and inducing the formation of rosette leaves on inflorescence stems. Genetic and gene expression analyses suggest that GIS acts in a GA-responsive pathway upstream of the trichome initiation regulator GLABROUS1 (GL1) and downstream of the GA signaling repressor SPINDLY (SPY). GIS mediates the induction of GL1 expression by GA in inflorescence organs and is antagonized in its action by the DELLA repressor GAI. The implication of GIS in the broader regulation of phase change is further suggested by the delay in flowering caused by GIS loss of function in the spy background. The discovery of GIS reveals a novel mechanism in the control of shoot maturation, through which GAs regulate cellular differentiation in plants.

  8. [Occlusion and posture: is there evidence of correlation?].

    PubMed

    Michelotti, A; Manzo, P; Farella, M; Martina, R

    1999-11-01

    The observation that the masticatory system and the postural body regulating system are anatomically and functionally related, has led to postulate several hypotheses of correlation between occlusal and postural disturbances. In the last decade, these arguments have gained a great social impact, also because they have been broadly spread by the mass-media. As a consequence, there has been a growing number of patients seeking concomitant occlusal and postural treatments. The aim of this study was to review critically the current evidence of correlation between the two systems; this in order to address clinical issues for the management of patients. Methodology of the studies reviewed has been evaluated according to the criteria suggested by Storey and Rugh 20 rif. Although there are some evidences of correlation between occlusion and posture, this appears limited to the cranio-cervical tract of the column and tends to disappear when descending in cranio-caudal direction. On the basis of this review of the literature, it's not advisable to treat postural imbalance by means of occlusal treatment or vice versa, particularly if the therapeutic modalities are irreversible.

  9. Heterotrimeric G Protein Signaling Is Required for Epidermal Cell Death in Rice[W][OA

    PubMed Central

    Steffens, Bianka; Sauter, Margret

    2009-01-01

    In rice (Oryza sativa) adventitious root primordia are formed at the nodes as part of normal development. Upon submergence of rice plants, adventitious roots emerge from the nodes preceded by death of epidermal cells above the root primordia. Cell death is induced by ethylene and mediated by hydrogen peroxide (H2O2). Pharmacological experiments indicated that epidermal cell death was dependent on signaling through G proteins. Treatment with GTP-γ-S induced epidermal cell death, whereas GDP-β-S partially inhibited ethylene-induced cell death. The dwarf1 (d1) mutant of rice has repressed expression of the Gα subunit RGA1 of heterotrimeric G protein. In d1 plants, cell death in response to ethylene and H2O2 was nearly completely abolished, indicating that signaling through Gα is essential. Ethylene and H2O2 were previously shown to alter gene expression in epidermal cells that undergo cell death. Transcriptional regulation was not generally affected in the d1 mutant, indicating that altered gene expression is not sufficient to trigger cell death in the absence of Gα. Analysis of genes encoding proteins related to G protein signaling revealed that four small GTPase genes, two GTPase-activating protein genes, and one GDP dissociation inhibitor gene but not RGA1 were differentially expressed in epidermal cells above adventitious roots, indicating that Gα activity is regulated posttranscriptionally. PMID:19656904

  10. Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium

    PubMed Central

    Delos Santos, Ralph Christian; Bautista, Stephen; Lucarelli, Stefanie; Bone, Leslie N.; Dayam, Roya M.; Abousawan, John; Botelho, Roberto J.; Antonescu, Costin N.

    2017-01-01

    Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question. We examined the selective regulation of clathrin-dependent EGFR signaling and endocytosis. We find that perturbations of phospholipase Cγ1 (PLCγ1), Ca2+, or protein kinase C (PKC) impair clathrin-mediated endocytosis of EGFR, the formation of CCPs harboring EGFR, and EGFR signaling. Each of these manipulations was without effect on the clathrin-mediated endocytosis of transferrin receptor (TfR). EGFR and TfR were recruited to largely distinct clathrin structures. In addition to control of initiation and assembly of CCPs, EGF stimulation also elicited a Ca2+- and PKC-dependent reduction in synaptojanin1 recruitment to clathrin structures, indicating broad control of CCP assembly by Ca2+ signals. Hence EGFR elicits PLCγ1-calcium signals to facilitate formation of a subset of CCPs, thus modulating its own signaling and endocytosis. This provides evidence for the versatility of CCPs to control diverse cellular processes. PMID:28814502

  11. Novel Mechanism for Regulation of Epidermal Growth Factor Receptor Endocytosis Revealed by Protein Kinase A Inhibition

    PubMed Central

    Salazar, Gloria; González, Alfonso

    2002-01-01

    Current models put forward that the epidermal growth factor receptor (EGFR) is efficiently internalized via clathrin-coated pits only in response to ligand-induced activation of its intrinsic tyrosine kinase and is subsequently directed into a lysosomal-proteasomal degradation pathway by mechanisms that include receptor tyrosine phosphorylation and ubiquitylation. Herein, we report a novel mechanism of EGFR internalization that does not require ligand binding, receptor kinase activity, or ubiquitylation and does not direct the receptor into a degradative pathway. Inhibition of basal protein kinase A (PKA) activity by H89 and the cell-permeable substrate peptide Myr-PKI induced internalization of 40–60% unoccupied, inactive EGFR, and its accumulation into early endosomes without affecting endocytosis of transferrin and μ-opioid receptors. This effect was abrogated by interfering with clathrin function. Thus, the predominant distribution of inactive EGFR at the plasma membrane is not simply by default but involves a PKA-dependent restrictive condition resulting in receptor avoidance of endocytosis until it is stimulated by ligand. Furthermore, PKA inhibition may contribute to ligand-induced EGFR endocytosis because epidermal growth factor inhibited 26% of PKA basal activity. On the other hand, H89 did not alter ligand-induced internalization of EGFR but doubled its half-time of down-regulation by retarding its segregation into degradative compartments, seemingly due to a delay in the receptor tyrosine phosphorylation and ubiquitylation. Our results reveal that PKA basal activity controls EGFR function at two levels: 1) residence time of inactive EGFR at the cell surface by a process of “endocytic evasion,” modulating the accessibility of receptors to stimuli; and 2) sorting events leading to the down-regulation pathway of ligand-activated EGFR, determining the length of its intracellular signaling. They add a new dimension to the fine-tuning of EGFR function

  12. Prefrontal Hemodynamic Changes Associated with Subjective Sense of Occlusal Discomfort

    PubMed Central

    Kobayashi, Goh; Hayama, Rika; Ikuta, Ryuhei; Onozouka, Minoru; Wake, Hiroyuki; Shimada, Atsushi; Shibuya, Tomoaki; Tamaki, Katsushi

    2015-01-01

    We used functional near-infrared spectroscopy to measure prefrontal brain activity accompanying the physical sensation of oral discomfort that arose when healthy young-adult volunteers performed a grinding motion with mild occlusal elevation (96 μm). We simultaneously evaluated various forms of occlusal discomfort using the visual analogue scale (VAS) and hemodynamic responses to identify the specific prefrontal activity that occurs with increased occlusal discomfort. The Oxy-Hb responses of selected channels in the bilateral frontopolar and dorsolateral prefrontal cortices increased in participants who reported increased severity of occlusal discomfort, while they decreased in those who reported no change or decreased occlusal discomfort during grinding. Moreover, the cumulative values of Oxy-Hb response in some of these channels were statistically significant predictive factors for the VAS scores. A generalized linear model analysis of Oxy-Hb signals in a group of participants who reported increased discomfort further indicated significant cerebral activation in the right frontopolar and dorsolateral prefrontal cortices that overlapped with the results of correlation analyses. Our results suggest that the increased hemodynamic responses in the prefrontal area reflect the top-down control of attention and/or self-regulation against the uncomfortable somatosensory input, which could be a possible marker to detect the subjective sense of occlusal discomfort. PMID:26090407

  13. ZNF750 is a p63 Target Gene that Induces KLF4 to Drive Terminal Epidermal Differentiation

    PubMed Central

    Sen, George L.; Boxer, Lisa D.; Webster, Dan E.; Bussat, Rose T.; Qu, Kun; Zarnegar, Brian J.; Johnston, Danielle; Siprashvili, Zurab; Khavari, Paul A.

    2012-01-01

    SUMMARY Disrupted epidermal differentiation characterizes numerous diseases that impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites flanking the transcriptional start site and controls its expression. ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process. PMID:22364861

  14. microRNA-184 Induces a Commitment Switch to Epidermal Differentiation.

    PubMed

    Nagosa, Sara; Leesch, Friederike; Putin, Daria; Bhattacharya, Swarnabh; Altshuler, Anna; Serror, Laura; Amitai-Lange, Aya; Nasser, Waseem; Aberdam, Edith; Rouleau, Matthieu; Tattikota, Sudhir G; Poy, Matthew N; Aberdam, Daniel; Shalom-Feuerstein, Ruby

    2017-12-12

    miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced clonogenicity and accelerated differentiation of human epidermal cells. We showed that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch activation and epidermal differentiation. The disease-causing miR-184 C57U mutant failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss-of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1, miR-184 regulates the transition from proliferation to early differentiation, while mis-expression or mutation in miR-184 results in impaired homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Optimization of the static occlusion by "occlusal surface settling" in the Cerec 3D software.

    PubMed

    Späth, C; Kordass, B

    2006-04-01

    The adjustment of the static occlusion can be automated in computer-based systems. The Cerec 3D software makes it possible to take preformed occlusal surfaces from a database and adapt them to the antagonist. In this adaptation (settling), the CAD occlusal surface "settles" as whole or each cusp individually into the occlusal surface of the antagonist until stable occlusion is reached. Two occlusal surface shapes were compared: Vita Physiodens and Lee Culp. An index was formed from the number, quality, and position of the occlusal contacts for 35 model cases (25 molars, 10 premolars). With regard to the settling of the total occlusal surfaces, there were no differences between the two occlusal surface shapes. In "cusp settling" of the molars, Vita Physiodens performed significantly better. In the comparison of the 1st with the 3rd settling process, significant improvements occurred the 3rd time in many cases when settling individual cusps, but in clearly fewer cases in the settling process of the total occlusal surface. The Lee Culp tooth occlusion improved especially after the 3rd settling process of individual cusps. It is therefore expedient to combine both settling versions with one another.

  16. Epidermal patterning genes are active during embryogenesis in Arabidopsis.

    PubMed

    Costa, Silvia; Dolan, Liam

    2003-07-01

    Epidermal cells in the root of Arabidopsis seedling differentiate either as hair or non-hair cells, while in the hypocotyl they become either stomatal or elongated cells. WEREWOLF (WER) and GLABRA2 (GL2) are positive regulators of non-hair and elongated cell development. CAPRICE (CPC) is a positive regulator of hair cell development in the root. We show that WER, GL2 and CPC are expressed and active during the stages of embryogenesis when the pattern of cells in the epidermis of the root-hypocotyl axis forms. GL2 is first expressed in the future epidermis in the heart stage embryo and its expression is progressively restricted to those cells that will acquire a non-hair identity in the transition between torpedo and mature stage. The expression of GL2 at the heart stage requires WER function. WER and CPC are transiently expressed throughout the root epidermal layer in the torpedo stage embryo when the cell-specific pattern of GL2 expression is being established in the epidermis. We also show that WER positively regulates CPC transcription and GL2 negatively regulates WER transcription in the mature embryo. We propose that the restriction of GL2 to the future non-hair cells in the root epidermis can be correlated with the activities of WER and CPC during torpedo stage. In the embryonic hypocotyl we show that WER controls GL2 expression. We also provide evidence indicating that CPC may also regulate GL2 expression in the hypocotyl.

  17. The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

    PubMed Central

    Large, Michael J.; Wetendorf, Margeaux; Lanz, Rainer B.; Hartig, Sean M.; Creighton, Chad J.; Mancini, Michael A.; Kovanci, Ertug; Lee, Kuo-Fen; Threadgill, David W.; Lydon, John P.; Jeong, Jae-Wook; DeMayo, Francesco J.

    2014-01-01

    Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets. PMID

  18. Hyaluronan Does Not Regulate Human Epidermal Keratinocyte Proliferation and Differentiation*

    PubMed Central

    Malaisse, Jérémy; Pendaries, Valérie; Hontoir, Fanny; De Glas, Valérie; Van Vlaender, Daniel; Simon, Michel; Lambert de Rouvroit, Catherine; Poumay, Yves; Flamion, Bruno

    2016-01-01

    Hyaluronan (HA) is synthesized by three HA synthases (HAS1, HAS2, and HAS3) and secreted in the extracellular matrix. In human skin, large amounts of HA are found in the dermis. HA is also synthesized by keratinocytes in the epidermis, although its epidermal functions are not clearly identified yet. To investigate HA functions, we studied the effects of HA depletion on human keratinocyte physiology within in vitro reconstructed human epidermis. Inhibition of HA synthesis with 4-methylumbelliferone (4MU) did not modify the expression profile of the epidermal differentiation markers involucrin, keratin 10, and filaggrin during tissue reconstruction. In contrast, when keratinocytes were incubated with 4MU, cell proliferation was decreased. In an attempt to rescue the proliferation function, HA samples of various mean molecular masses were added to keratinocyte cultures treated with 4MU. These samples were unable to rescue the initial proliferation rate. Furthermore, treatments with HA-specific hyaluronidase, although removing almost all HA from keratinocyte cultures, did not alter the differentiation or proliferation processes. The differences between 4MU and hyaluronidase effects did not result from differences in intracellular HA, sulfated glycosaminoglycan concentration, apoptosis, or levels of HA receptors, all of which remained unchanged. Similarly, knockdown of UDP-glucose 6-dehydrogenase (UGDH) using lentiviral shRNA effectively decreased HA production but did not affect proliferation rate. Overall, these data suggest that HA levels in the human epidermis are not directly correlated with keratinocyte proliferation and differentiation and that incubation of cells with 4MU cannot equate with HA removal. PMID:26627828

  19. Analysis of decrease in lung perfusion blood volume with occlusive and non-occlusive pulmonary embolisms.

    PubMed

    Ikeda, Yohei; Yoshimura, Norihiko; Hori, Yoshiro; Horii, Yosuke; Ishikawa, Hiroyuki; Yamazaki, Motohiko; Noto, Yoshiyuki; Aoyama, Hidefumi

    2014-12-01

    The aim of this study was to determine if lung perfusion blood volume (lung PBV) with non-occlusive pulmonary embolism (PE) differs quantitatively and visually from that with occlusive PE and to investigate if lung PBV with non-occlusive PE remains the same as that without PE. Totally, 108 patients suspected of having acute PE underwent pulmonary dual-energy computed tomography angiography (DECTA) between April 2011 and January 2012. Presence of PE on DECTA was evaluated by one radiologist. Two radiologists visually evaluated the PE distribution (segmental or subsegmental) and its nature (occlusive or non-occlusive) on DECTA and classified perfusion in lung PBV as "decreased," "slightly decreased," and "preserved". Two radiologists used a lung PBV application to set a region of interest (ROI) in the center of the lesion and measured HU values of an iodine map. In the same slice as the ROI of the lesion and close to the lesion, another ROI was set in the normal perfusion area without PE, and HUs were measured. The proportion of lesions was compared between the occlusive and non-occlusive groups. HUs were compared among the occlusive, non-occlusive, and corresponding normal groups. Twenty-five patients had 80 segmental or subsegmental lesions. There were 37 and 43 lesions in the occlusive and non-occlusive groups, respectively. The proportion of decreased lesions was 73.0% (27/37) in the occlusive group, while that of preserved lesions in the non-occlusive group was 76.7% (33/43). There was a significant difference in the proportion of lesions (P<0.001) between the two groups. HUs of the iodine map were significantly higher in the non-occlusive group than in the occlusive group (33.8 ± 8.2 HU vs. 11.9 ± 6.1 HU, P<0.001). There was no significant difference in HUs for the entire lesion between the non-occlusive (33.8 ± 8.2 HU) and corresponding normal group (34.5 ± 6.8 HU; P=0.294). Iodine perfusion tended to be visually and quantitatively preserved in lungs with

  20. Effect of occlusion amblyopia after prescribed full-time occlusion on long-term visual acuity outcomes.

    PubMed

    Longmuir, Susannah; Pfeifer, Wanda; Scott, William; Olson, Richard

    2013-01-01

    To investigate the incidence and characteristics of occlusion amblyopia with prescribed full-time patching and determine its effect on long-term visual acuity outcomes. The records of patients younger than 10 years diagnosed as having amblyopia between 1970 and 2000 were retrospectively reviewed. Patients were prescribed full-time occlusion and observed until completion of therapy. Of 597 patients treated for amblyopia by full-time patching, 115 were diagnosed as having occlusion amblyopia (19.3%). Seventy-five percent (86 of 115) developed occlusion amblyopia during the first episode of full-time patching. Occlusion amblyopia occurred more frequently in children prescribed full-time patching at an earlier age (P = .0002), with an odds ratio of 8.56 (95% confidence interval: 2.73, 26.84) in children younger than 36 months and 2.66 (95% confidence interval: 0.96, 7.37) in children between 36 and 59 months old. Seven of the patients with occlusion amblyopia did not reverse fixation and continued to fixate with the initially amblyopic eye after treatment. Final visual acuity in these eyes with occlusion amblyopia was 20/30 or better. After cessation of treatment, the final interocular difference in visual acuity was less in patients with a history of occlusion amblyopia (P = .003). Occlusion amblyopia occurred at all ages, but the incidence decreased with increasing age. Patients who developed occlusion amblyopia with prescribed full-time occlusion had less interocular visual acuity difference than patients who did not, suggesting that development of occlusion amblyopia can indicate the potential for the development of better vision in the originally amblyopic eye. Copyright 2013, SLACK Incorporated.

  1. Epidermal cyst mimicking incision line metastasis.

    PubMed

    Gündoğdu, Ramazan; Ayhan, Erhan; Çolak, Tahsin

    2017-01-01

    Epidermal cysts are cystic tumors lined with keratinized squamous layer and filled with keratin debris. Epidermal cysts may develop by implantation of surface epidermal layer into the dermis or subcutaneous tissue after trauma or surgical procedures. Cervix cancer spreads either directly or via the vascular and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is very rare. In this case report, a patient who had a history of cervix cancer operation 11 years ago and presented with a mass that mimicked incision line metastasis and was histopathologically diagnosed with epidermal cyst is presented.

  2. Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium.

    PubMed

    Delos Santos, Ralph Christian; Bautista, Stephen; Lucarelli, Stefanie; Bone, Leslie N; Dayam, Roya M; Abousawan, John; Botelho, Roberto J; Antonescu, Costin N

    2017-10-15

    Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question. We examined the selective regulation of clathrin-dependent EGFR signaling and endocytosis. We find that perturbations of phospholipase Cγ1 (PLCγ1), Ca 2+ , or protein kinase C (PKC) impair clathrin-mediated endocytosis of EGFR, the formation of CCPs harboring EGFR, and EGFR signaling. Each of these manipulations was without effect on the clathrin-mediated endocytosis of transferrin receptor (TfR). EGFR and TfR were recruited to largely distinct clathrin structures. In addition to control of initiation and assembly of CCPs, EGF stimulation also elicited a Ca 2+ - and PKC-dependent reduction in synaptojanin1 recruitment to clathrin structures, indicating broad control of CCP assembly by Ca 2+ signals. Hence EGFR elicits PLCγ1-calcium signals to facilitate formation of a subset of CCPs, thus modulating its own signaling and endocytosis. This provides evidence for the versatility of CCPs to control diverse cellular processes. © 2017 Delos Santos et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1

    PubMed Central

    Ambler, Carrie A.; Watt, Fiona M.

    2010-01-01

    Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin. PMID:20940224

  4. Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1.

    PubMed

    Ambler, Carrie A; Watt, Fiona M

    2010-11-01

    Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin.

  5. A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells.

    PubMed

    Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi

    2016-04-01

    Plant leaf epidermal cells exhibit a jigsaw puzzle-like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo.

  6. A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells

    PubMed Central

    Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi

    2016-01-01

    Plant leaf epidermal cells exhibit a jigsaw puzzle–like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo. PMID:27054467

  7. Numeric simulation of occlusal interferences in molars restored with ultrathin occlusal veneers.

    PubMed

    Magne, Pascal; Cheung, Raymond

    2017-01-01

    Selecting material for a minimally invasive occlusal veneer reconstruction concept requires an understanding of how stresses are distributed during functional and parafunctional forces. The purpose of this in vitro study was to investigate stress distribution in a maxillary molar restored with ultrathin occlusal veneers and subjected by an antagonistic mandibular molar to clenching and working and nonworking movements. A maxillary first molar was modeled from microcomputed tomography (micro-CT) data, using medical image processing software, stereolithography editing/optimizing software, and finite element software. Simulated ultrathin occlusal veneer materials were used. The mandibular molar antagonist was a solid nondeformable geometric entity. Loads simulated clenching, working, and nonworking movements with loading of 500 N. The values of the maximum principal stress were recorded. In the clenching load situation, maximum tensile stresses were located at the occlusal veneer (52 MPa for composite resin versus 47 MPa for ceramic). In the working movement, significant additional tensile stresses were found on the palatal root (87 MPa for composite resin and 85 MPa for ceramic). In the nonworking movement, tensile stress on the ultrathin occlusal veneer increased to 118 MPa for composite resin and 143 MPa for ceramic veneers. Tensile stress peaks shifted to the mesiobuccal root (75 MPa for composite resin and 74 MPa for ceramic). The topography of stresses generated by the various occlusal interferences were clearly identified. Significant tensile stress concentrations were found within the restoration's occlusal topography and root, with the nonworking interference being the most harmful and also the most revealing of the difference between the composite resin and ceramic ultrathin occlusal veneers. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  8. Epidermal cyst mimicking incision line metastasis

    PubMed Central

    Gündoğdu, Ramazan; Ayhan, Erhan; Çolak, Tahsin

    2017-01-01

    Epidermal cysts are cystic tumors lined with keratinized squamous layer and filled with keratin debris. Epidermal cysts may develop by implantation of surface epidermal layer into the dermis or subcutaneous tissue after trauma or surgical procedures. Cervix cancer spreads either directly or via the vascular and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is very rare. In this case report, a patient who had a history of cervix cancer operation 11 years ago and presented with a mass that mimicked incision line metastasis and was histopathologically diagnosed with epidermal cyst is presented. PMID:28740968

  9. Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice

    PubMed Central

    Shi, Yu-Ling; Gu, Jun; Park, Jun-Yang; Xu, Ying-Ping; Yu, Fu-Shin; Zhou, Li; Mi, Qing-Sheng

    2012-01-01

    Background Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs). Objective The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development. Methods ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleens and skin draining lymph nodes were collected for immune staining. Results TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4+ and CD8+ T cells, Foxp3+CD4+ regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice. Conclusion Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases. PMID:22999682

  10. Quantitative description of human skin water dynamics by a disposition-decomposition analysis (DDA) of trans-epidermal water loss and epidermal capacitance.

    PubMed

    Rodrigues, Luis Monteiro; Pinto, Pedro Contreiras; Pereira, Luis Marcelo

    2003-02-01

    In vivo water assessment would greatly benefit from a dynamical approach since the evaluation of common related variables such as trans-epidermal water loss or "capacitance" measurements is always limited to instantaneous data. Mathematical modelling is still an attractive alternative already attempted with bi-exponential empirical models. A classical two-compartment interpretation of such models raises a number of questions about the underlying fundamentals, which can hardly be experimentally confirmed. However, in a system analysis sense, skin water dynamics may be approached as an ensemble of many factors, impossible to discretize, but conceptually grouped in terms of feasible properties of the system. The present paper explores the applicability of this strategy to the in vivo water dynamics assessment. From the plastic occlusion stress test (POST) skin water balance is assessed by modelling trans-epidermal water loss (TEWL) and "capacitance" data obtained at skin's surface. With system analysis (disposition-decomposition analysis) the distribution function, H(t), modelled as a sum of exponential terms, covers only the distribution characteristics of water molecules traversing the skin. This may correspond macroscopically to the experimental data accessed by "corneometry". Separately, the hyperbolic elimination function Q(TEWL) helps to characterise the dynamic aspects of water influx through the skin. In the observable range there seems to be a linear relationship between the net amount of water lost at the surface by evaporation, and the capability of the system to replenish that loss. This may be a specific characteristic of the system related to what may be described as the skin's "intrinsic hydration capacity" (IHC) a new functional parameter only identified by this strategy. These new quantitative tools are expected to find different applicabilities (from the in vivo skin characterisation to efficacy testing) contributing to disclose the dynamical nature

  11. Diagnosis of occlusal dysesthesia utilizing prefrontal hemodynamic activity with slight occlusal interference.

    PubMed

    Ono, Yumie; Ishikawa, Yu; Munakata, Motohiro; Shibuya, Tomoaki; Shimada, Atsushi; Miyachi, Hideo; Wake, Hiroyuki; Tamaki, Katsushi

    2016-11-01

    Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite the persistent complaint of uncomfortable bite sensation. We previously demonstrated that the subjective feeling of occlusal discomfort generated by artificial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young healthy individuals. The aim of this study was to investigate whether dental patients with and without OD show distinct prefrontal activity during grinding behavior with an occlusal interference. Six dental patients with OD (OD group) and eight patients without OD (control group) grinded piled occlusal strips placed between their first molars and reported their perception and discomfort thresholds during continuous monitoring of prefrontal hemodynamic activity with a portable functional near-infrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb) concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they executed grinding. The intensities of the task-related HHb activities showed statistically significant differences between OD and control groups, particularly at channel 3, arranged over the left frontal pole cortex. When the discrimination criterion was set using the intensity values of channel 3 from both groups, the overall accuracy of the OD discrimination was 92.9%. Although physiological interpretation has yet to be elucidated, the task-related response of an increase in HHb may be a useful neuronal signature to characterize dental patients with OD.

  12. Diagnosis of occlusal dysesthesia utilizing prefrontal hemodynamic activity with slight occlusal interference

    PubMed Central

    Ishikawa, Yu; Munakata, Motohiro; Shibuya, Tomoaki; Shimada, Atsushi; Miyachi, Hideo; Wake, Hiroyuki; Tamaki, Katsushi

    2016-01-01

    Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite the persistent complaint of uncomfortable bite sensation. We previously demonstrated that the subjective feeling of occlusal discomfort generated by artificial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young healthy individuals. The aim of this study was to investigate whether dental patients with and without OD show distinct prefrontal activity during grinding behavior with an occlusal interference. Six dental patients with OD (OD group) and eight patients without OD (control group) grinded piled occlusal strips placed between their first molars and reported their perception and discomfort thresholds during continuous monitoring of prefrontal hemodynamic activity with a portable functional near‐infrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb) concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they executed grinding. The intensities of the task‐related HHb activities showed statistically significant differences between OD and control groups, particularly at channel 3, arranged over the left frontal pole cortex. When the discrimination criterion was set using the intensity values of channel 3 from both groups, the overall accuracy of the OD discrimination was 92.9%. Although physiological interpretation has yet to be elucidated, the task‐related response of an increase in HHb may be a useful neuronal signature to characterize dental patients with OD. PMID:29744159

  13. Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

    PubMed Central

    Lladó, Anna; Timpson, Paul; Vilà de Muga, Sandra; Moretó, Jemina; Pol, Albert; Grewal, Thomas; Daly, Roger J.

    2008-01-01

    The intracellular trafficking of the epidermal growth factor receptor (EGFR) is regulated by a cross-talk between calmodulin (CaM) and protein kinase Cδ (PKCδ). On inhibition of CaM, PKCδ promotes the formation of enlarged early endosomes and blocks EGFR recycling and degradation. Here, we show that PKCδ impairs EGFR trafficking due to the formation of an F-actin coat surrounding early endosomes. The PKCδ-induced polymerization of actin is orchestrated by the Arp2/3 complex and requires the interaction of cortactin with PKCδ. Accordingly, inhibition of actin polymerization by using cytochalasin D or by overexpression of active cofilin, restored the normal morphology of the organelle and the recycling of EGFR. Similar results were obtained after down-regulation of cortactin and the sequestration of the Arp2/3 complex. Furthermore we demonstrate an interaction of cortactin with CaM and PKCδ, the latter being dependent on CaM inhibition. In summary, this study provides the first evidence that CaM and PKCδ organize actin dynamics in the early endosomal compartment, thereby regulating the intracellular trafficking of EGFR. PMID:17959830

  14. Partial Resuscitative Endovascular Balloon Occlusion of the Aorta (P-REBOA) in a Pig Model (Sus scrofa) with ongoing Resuscitation

    DTIC Science & Technology

    2016-01-08

    occlusion, regulated flow provided perfusion to capillary beds. Following 70 minutes of partial aortic occlusion, damage control surgery and whole blood ... renal function, and were weaned from aortic occlusion more rapidly. CONCLUSIONS: P-REBOA is capable of limiting exsanguination while providing blood ...resuscitation was performed and all animals were survived to 360 minutes. Animals that tolerated distal flow had decreased levels of lactate, preserved

  15. Steroids are required for epidermal cell fate establishment in Arabidopsis roots.

    PubMed

    Kuppusamy, Kavitha T; Chen, Andrew Y; Nemhauser, Jennifer L

    2009-05-12

    The simple structure of Arabidopsis roots provides an excellent model system to study epidermal cell fate specification. Epidermal cells in contact with 2 underlying cortical cells differentiate into hair cells (H cells; trichoblasts), whereas cells that contact only a single cortical cell differentiate into mature hairless cells (N cells; atrichoblasts). This position-dependent patterning, in combination with the constrained orientation of cell divisions, results in hair and nonhair cell files running longitudinally along the root epidermis. Here, we present strong evidence that steroid hormones called brassinosteroids (BRs) are required to maintain position-dependent fate specification in roots. We show that BRs are required for normal expression levels and patterns of WEREWOLF (WER) and GLABRA2 (GL2), master regulators of epidermal patterning. Loss of BR signaling results in loss of hair cells in H positions, likely as a consequence of reduced expression of CAPRICE (CPC), a direct downstream target of WER. Our observations demonstrate that in addition to their well-known role in cell expansion, BRs play an essential role in directing cell fate.

  16. Steroids are required for epidermal cell fate establishment in Arabidopsis roots

    PubMed Central

    Kuppusamy, Kavitha T.; Chen, Andrew Y.; Nemhauser, Jennifer L.

    2009-01-01

    The simple structure of Arabidopsis roots provides an excellent model system to study epidermal cell fate specification. Epidermal cells in contact with 2 underlying cortical cells differentiate into hair cells (H cells; trichoblasts), whereas cells that contact only a single cortical cell differentiate into mature hairless cells (N cells; atrichoblasts). This position-dependent patterning, in combination with the constrained orientation of cell divisions, results in hair and nonhair cell files running longitudinally along the root epidermis. Here, we present strong evidence that steroid hormones called brassinosteroids (BRs) are required to maintain position-dependent fate specification in roots. We show that BRs are required for normal expression levels and patterns of WEREWOLF (WER) and GLABRA2 (GL2), master regulators of epidermal patterning. Loss of BR signaling results in loss of hair cells in H positions, likely as a consequence of reduced expression of CAPRICE (CPC), a direct downstream target of WER. Our observations demonstrate that in addition to their well-known role in cell expansion, BRs play an essential role in directing cell fate. PMID:19416891

  17. Selective Matrix (Hyaluronan) Interaction with CD44 and RhoGTPase Signaling Promotes Keratinocyte Functions and Overcomes Age-related Epidermal Dysfunction

    PubMed Central

    Bourguignon, Lilly Y.W.; Wong, Gabriel; Xia, Weiliang; Man, Mao-Qiang; Holleran, Walter M.; Elias, Peter M.

    2013-01-01

    Background Mouse epidermal chronologic aging is closely associated with aberrant matrix (hyaluronan, HA) -size distribution/production and impaired keratinocyte proliferation/differentiation, leading to a marked thinning of the epidermis with functional consequence that causes a slower recovery of permeability barrier function. Objective The goal of this study is to demonstrate mechanism-based, corrective therapeutic strategies using topical applications of small HA (HAS) and/or large HA (HAL) [or a sequential small HA (HAS) and large HA(HAL) (HAs-»HAL) treatment] as well as RhoGTPase signaling perturbation agents to regulate HA/CD44-mediated signaling, thereby restoring normal epidermal function, and permeability barrier homeostasis in aged mouse skin. Methods A number of biochemical, cell biological/molecular, pharmacological and physiological approaches were used to investigate matrix HA-CD44-mediated RhoGTPase signaling in regulating epidermal functions and skin aging. Results In this study we demonstrated that topical application of small HA (HAS) promotes keratinocyte proliferation and increases skin thickness, while it fails to upregulate keratinocyte differentiation or permeability barrier repair in aged mouse skin. In contrast, large HA (HAL) induces only minimal changes in keratinocyte proliferation and skin thickness, but restores keratinocyte differentiation and improves permeability barrier function in aged epidermis. Since neither HAS nor HAL corrects these epidermal defects in aged CD44 knock-out mice, CD44 likely mediates HA-associated epidermal functions in aged mouse skin. Finally, blockade of Rho-kinase activity with Y27632 or protein kinase-Nγ activity with Ro31-8220 significantly decreased the HA (HAS or HAL)-mediated changes in epidermal function in aged mouse skin. Conclusion The results of our study show first that HA application of different sizes regulates epidermal proliferation, differentiation and barrier function in aged mouse skin

  18. ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis

    PubMed Central

    Shalom-Feuerstein, R; Lena, A M; Zhou, H; De La Forest Divonne, S; Van Bokhoven, H; Candi, E; Melino, G; Aberdam, D

    2011-01-01

    p63, a member of p53 family, has a significant role in the development and maintenance of stratified epithelia. However, a persistent dispute remained over the last decade concerning the interpretation of the severe failure of p63-null embryos to develop stratified epithelia. In this study, by investigating both p63-deficient strains, we demonstrated that p63-deficient epithelia failed to develop beyond ectodermal stage as they remained a monolayer of non-proliferating cells expressing K8/K18. Importantly, in the absence of p63, corneal-epithelial commitment (which occurs at embryonic day 12.5 of mouse embryogenesis) was hampered 3 weeks before corneal stem cell renewal (that begins at P14). Taken together, these data illustrate the significant role of p63 in epithelial embryogenesis, before and independently of other functions of p63 in adult stem cells regulation. Transcriptome analysis of laser captured-embryonic tissues confirmed the latter hypothesis, demonstrating that a battery of epidermal genes that were activated in wild-type epidermis remained silent in p63-null tissues. Furthermore, we defined a subset of novel bona fide p63-induced genes orchestrating first epidermal stratification and a subset of p63-repressed mesodermal-specific genes. These data highlight the earliest recognized action of ΔNp63 in the induction epidermal morphogenesis at E11.5. In the absence of p63, a mesodermal program is activated while epidermal morphogenesis does not initiate. PMID:21127502

  19. A dermal HOX transcriptional program regulates site-specific epidermal fate

    PubMed Central

    Rinn, John L.; Wang, Jordon K.; Allen, Nancy; Brugmann, Samantha A.; Mikels, Amanda J.; Liu, Helen; Ridky, Todd W.; Stadler, H. Scott; Nusse, Roel; Helms, Jill A.; Chang, Howard Y.

    2008-01-01

    Reciprocal epithelial–mesenchymal interactions shape site-specific development of skin. Here we show that site-specific HOX expression in fibroblasts is cell-autonomous and epigenetically maintained. The distal-specific gene HOXA13 is continually required to maintain the distal-specific transcriptional program in adult fibroblasts, including expression of WNT5A, a morphogen required for distal development. The ability of distal fibroblasts to induce epidermal keratin 9, a distal-specific gene, is abrogated by depletion of HOXA13, but rescued by addition of WNT5A. Thus, maintenance of appropriate HOX transcriptional program in adult fibroblasts may serve as a source of positional memory to differentially pattern the epithelia during homeostasis and regeneration. PMID:18245445

  20. A dermal HOX transcriptional program regulates site-specific epidermal fate.

    PubMed

    Rinn, John L; Wang, Jordon K; Allen, Nancy; Brugmann, Samantha A; Mikels, Amanda J; Liu, Helen; Ridky, Todd W; Stadler, H Scott; Nusse, Roel; Helms, Jill A; Chang, Howard Y

    2008-02-01

    Reciprocal epithelial-mesenchymal interactions shape site-specific development of skin. Here we show that site-specific HOX expression in fibroblasts is cell-autonomous and epigenetically maintained. The distal-specific gene HOXA13 is continually required to maintain the distal-specific transcriptional program in adult fibroblasts, including expression of WNT5A, a morphogen required for distal development. The ability of distal fibroblasts to induce epidermal keratin 9, a distal-specific gene, is abrogated by depletion of HOXA13, but rescued by addition of WNT5A. Thus, maintenance of appropriate HOX transcriptional program in adult fibroblasts may serve as a source of positional memory to differentially pattern the epithelia during homeostasis and regeneration.

  1. 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.

  2. Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells

    PubMed Central

    Wang, Lihong; Cao, Hailong; Lu, Ning; Liu, Liping; Wang, Bangmao; Hu, Tianhui; Israel, Dawn A.; Peek, Richard M.; Polk, D. Brent; Yan, Fang

    2013-01-01

    Berberine, an isoquinoline alkaloid, is an active component of Ranunculaceae and Papaveraceae plant families. Berberine has been found to suppress growth of several tumor cell lines in vitro through the cell-type-dependent mechanism. Expression and activation of epidermal growth factor receptor (EGFR) is increased in colonic precancerous lesions and tumours, thus EGFR is considered a tumour promoter. The aim of this study was to investigate the effects and mechanisms of berberine on regulation of EGFR activity and proliferation in colonic tumor cell lines and in vivo. We reported that berberine significantly inhibited basal level and EGF-stimulated EGFR activation and proliferation in the immorto Min mouse colonic epithelial (IMCE) cells carrying the APC min mutation and human colonic carcinoma cell line, HT-29 cells. Berberine acted to inhibit proliferation through inducing G1/S and G2/M cell cycle arrest, which correlated with regulation of the checkpoint protein expression. In this study, we also showed that berberine stimulated ubiquitin ligase Cbl activation and Cbl's interaction with EGFR, and EGFR ubiquitinylation and down-regulation in these two cell lines in the presence or absence of EGF treatment. Knock-down Cbl expression blocked the effects of berberine on down-regulation of EGFR and inhibition of proliferation. Furthermore, berberine suppressed tumor growth in the HT-29 cell xenograft model. Cell proliferation and EGFR expression level was decreased by berberine treatment in this xenograft model and in colon epithelial cells of APC min/+ mice. Taken together, these data indicate that berberine enhances Cbl activity, resulting in down-regulation of EGFR expression and inhibition of proliferation in colon tumor cells. PMID:23457600

  3. 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon isolated from marine algae-derived microorganisms induce down regulation of epidermal growth factor activated mitogenic signaling cascade in Hela cells.

    PubMed

    Jo, Mi Jeong; Bae, Seong Ja; Son, Byeng Wha; Kim, Chi Yeon; Kim, Gun Do

    2013-05-25

    Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase (RTK) family. Epidermal growth factor induces its dimerization and stimulates phosphorylation of intracellular tyrosine residues. Phosphorylation of EGFR is studied for cancer therapy because EGFR regulates many cellular processes including cell proliferation, differentiation, and survival. Hence, down-regulation of EGFR kinase activity results in inhibition of signaling cascades amenable for proliferation and progression of cell cycle. In the study, we purified 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon from Aspergillus sp. isolated from marine brown alga Ishige okamurae and Phoma herbarum isolated from marine red alga Hypnea saidana respectively and determined its anti-tumor activities against HeLa human cervical cancer cells. Two compounds suppressed EGFR activity in vitro with IC50 values for 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon were 2.8 and 0.6 μg/mL respectively and reduced the viable numbers of HeLa cells. Immunoblotting analysis exhibited that the compounds induced inhibition of cell growth by causing downregulation of the mitogenic signaling cascade, inactivation of p90RSK, and release of cytochrome c from mitochondria. Results suggest that decreased expression of active EGFR and EGFR-related downstream molecules by treatment with the compounds may results in the inhibition of cell growth and inducement of apoptosis.

  4. Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression.

    PubMed

    Li, Junqin; Li, Xinhua; Hou, Ruixia; Liu, Ruifeng; Zhao, Xincheng; Dong, Feng; Wang, Chunfang; Yin, Guohua; Zhang, Kaiming

    2015-09-01

    Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR. mRNA expression patterns were investigated by RNA sequencing and verified by real-time reverse transcription polymerase chain reaction. After co-culture with psoriatic T cells, the expression of Ki-67, c-Myc and p53 increased, while expression of Bcl-2 and epidermal turnover time decreased. There were 14 DEG which were found to participate in the regulation of cell proliferation or differentiation. Psoriatic T cells exhibited the ability to decrease epidermal turnover time and affect keratinocyte proliferation because of the differential expression of PPIL1, HSPH1, SENP3, NUP54, FABP5, PLEKHG3, SLC9A9 and CHCHD4. © 2015 Japanese Dermatological Association.

  5. Contralateral Occlusion Test: The effect of external ear canal occlusion on hearing thresholds.

    PubMed

    Reis, Luis Roque; Fernandes, Paulo; Escada, Pedro

    Bedside testing with tuning forks may decrease turnaround time and improve decision making for a quick qualitative assessment of hearing loss. The purpose of this study was to quantify the effects of ear canal occlusion on hearing, in order to decide which tuning fork frequency is more appropriate to use for quantifying hearing loss with the Contralateral Occlusion Test. Twenty normal-hearing adults (forty ears) underwent sound field pure tone audiometry with and without ear canal occlusion. Each ear was tested with the standard frequencies. The contralateral ear was suppressed with by masking. Ear occlusion was performed by two examiners. Participants aged between 21 and 30 years (25.6±3.03 years) showed an increase in hearing thresholds with increasing frequencies from 19.94dB (250Hz) to 39.25dB (2000Hz). The threshold difference between occluded and unoccluded conditions was statistically significant and increased from 10.69dB (250Hz) to 32.12dB (2000Hz). There were no statistically significant differences according to gender or between the examiners. The occlusion effect increased the hearing thresholds and became more evident with higher frequencies. The occlusion method as performed demonstrated reproducibility. In the Contralateral Occlusion Test, 256Hz or 512Hz tuning forks should be used for diagnosis of mild hearing loss, and a 2048Hz tuning fork should be used for moderate hearing loss. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  6. Epidermal growth factor system is a physiological regulator of development of the mouse fetal submandibular gland and regulates expression of the alpha6-integrin subunit.

    PubMed

    Kashimata, M; Gresik, E W

    1997-02-01

    Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) regulate branching morphogenesis of fetal mouse submandibular gland (SMG) rudiments in vitro. The EGF system (EGF, TGF-alpha, and their shared receptor, EGFR) also regulates expression of integrins and their ligands in the extracellular matrix. We show here that inhibition of EGFR tyrosine-kinase activity by a tyrphostin retards in vitro development of SMGs. Using total RNA isolated from pooled SMGs taken from intact mouse fetuses, mRNA transcripts for EGF, TGF-alpha, and EGFR were detected by reverse transcription-polymerase chain reaction (RT-PCR), and age-dependent variations in the levels of these mRNA were quantitatively determined by nuclease protection assays. These findings suggest that the EGF system is operative in the in vivo development of this gland. alpha6-Integrin subunit was localized by immunofluorescence at the basal surface of epithelial cells. Branching morphogenesis of cultured SMG rudiments was inhibited by anti-alpha6 antibodies. Synthesis of alpha6-subunit in cultured SMGs, detected by metabolic labeling and immunoprecipitation, was increased by EGF and drastically reduced by tyrphostin. RT-PCR revealed that mRNAs for alpha6- and beta1- and beta4-integrin subunits are expressed at all ages between embryonic day 13 and postnatal day 7. These findings suggest that 1) the EGF system is a physiologic regulator of development of fetal mouse SMG, and 2) one mechanism by which it acts may be by regulating expression of integrins, which in turn control interaction of epithelial cells with the extracellular matrix.

  7. 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

  8. Expression of ZO-1 and claudin-1 in a 3D epidermal equivalent using canine progenitor epidermal keratinocytes.

    PubMed

    Teramoto, Keiji; Asahina, Ryota; Nishida, Hidetaka; Kamishina, Hiroaki; Maeda, Sadatoshi

    2018-05-21

    Previous studies indicate that tight junctions are involved in the pathogenesis of canine atopic dermatitis (cAD). An in vitro skin model is needed to elucidate the specific role of tight junctions in cAD. A 3D epidermal equivalent model using canine progenitor epidermal keratinocytes (CPEK) has been established; the expression of tight junctions within this model is uncharacterized. To investigate the expression of tight junctions in the 3D epidermal equivalent. Two normal laboratory beagle dogs served as donors of full-thickness skin biopsy samples for comparison to the in vitro model. Immunohistochemical techniques were employed to investigate the expression of tight junctions including zonula occludens (ZO)-1 and claudin-1 in normal canine skin, and in the CPEK 3D epidermal equivalent. Results demonstrated the expression of ZO-1 and claudin-1 in the CPEK 3D epidermal equivalent, with staining patterns that were similar to those in normal canine skin. The CPEK 3D epidermal equivalent has the potential to be a suitable in vitro research tool for clarifying the specific role of tight junctions in cAD. © 2018 ESVD and ACVD.

  9. [Effect of 2 methods of occlusion adjustment on occlusal balance and muscles of mastication in patient with implant restoration].

    PubMed

    Wang, Rong; Xu, Xin

    2015-12-01

    To compare the effect of 2 methods of occlusion adjustment on occlusal balance and muscles of mastication in patients with dental implant restoration. Twenty patients, each with a single edentulous posterior dentition with no distal dentition were selected, and divided into 2 groups. Patients in group A underwent original occlusion adjustment method and patients in group B underwent occlusal plane reduction technique. Ankylos implants were implanted in the edentulous space in each patient and restored with fixed prosthodontics single unit crown. Occlusion was adjusted in each restoration accordingly. Electromyograms were conducted to determine the effect of adjustment methods on occlusion and muscles of mastication 3 months and 6 months after initial restoration and adjustment. Data was collected and measurements for balanced occlusal measuring standards were obtained, including central occlusion force (COF), asymmetry index of molar occlusal force(AMOF). Balanced muscles of mastication measuring standards were also obtained including measurements from electromyogram for the muscles of mastication and the anterior bundle of the temporalis muscle at the mandibular rest position, average electromyogram measurements of the anterior bundle of the temporalis muscle at the intercuspal position(ICP), Astot, masseter muscle asymmetry index, and anterior temporalis asymmetry index (ASTA). Statistical analysis was performed using Student 's t test with SPSS 18.0 software package. Three months after occlusion adjustment, parameters of the original occlusion adjustment method were significantly different between group A and group B in balanced occlusal measuring standards and balanced muscles of mastication measuring standards. Six months after occlusion adjustment, parameters of the original occlusion adjustment methods were significantly different between group A and group B in balanced muscles of mastication measuring standards, but was no significant difference in balanced

  10. Carbon Dioxide Metabolism in Leaf Epidermal Tissue 1

    PubMed Central

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

    1973-01-01

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

  11. Acute stroke with major intracranial vessel occlusion: Characteristics of cardioembolism and atherosclerosis-related in situ stenosis/occlusion.

    PubMed

    Horie, Nobutaka; Tateishi, Yohei; Morikawa, Minoru; Morofuji, Yoichi; Hayashi, Kentaro; Izumo, Tsuyoshi; Tsujino, Akira; Nagata, Izumi; Matsuo, Takayuki

    2016-10-01

    Acute ischemic stroke with major intracranial vessel occlusion is commonly due to cardioembolic or atherosclerosis-related in situ stenosis/occlusion, and immediate identification of these subtypes is important to establish the optimal treatment strategy. The aim of this study was to clarify the differences in clinical presentation, radiological findings, neurological temporal courses, and outcomes between these etiologies, which have not been fully evaluated. Consecutive emergency patients with acute ischemic stroke were retrospectively reviewed. Among them, patients with stroke with major intracranial vessel occlusion were analyzed with a focus on clinical and radiological findings, and a comparison was performed for those with cardioembolic or atherosclerosis-related in situ stenosis/occlusion. Of 1053 patients, 80 had stroke with acute major intracranial vessel occlusion (45 with cardioembolic and 35 with atherosclerosis-related in situ stenosis/occlusion). Interestingly, the susceptibility vessel sign (SVS) on T2-weighted MR angiography was more frequently detected in cardioembolic stroke (80.0%) than in atherosclerosis (in situ stenosis: 5.9%, chronic occlusion: 14.3%). Moreover, the proximal intra-arterial signal (IAS) on arterial spin labeling MRI and the distal IAS on fluid attenuated inversion recovery MRI was less frequently detected in chronic occlusion (27.3% and 50.0%, respectively) than in acute occlusion due to cardioembolic or in situ stenosis. Multivariate regression analysis showed that the SVS was significantly related to cardioembolism (adjusted odds ratio (OR): 21.68, P=0.004). Clinical characteristics of acute stroke with major intracranial vessel occlusion differ depending on the etiology. The SVS and proximal/distal IAS on MRI are useful to distinguish between cardioembolic and atherosclerotic-related in situ stenosis/occlusion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Ricinus communis-based biopolymer and epidermal growth factor regulations on bone defect repair: A rat tibia model

    NASA Astrophysics Data System (ADS)

    Mendoza-Barrera, C.; Meléndez-Lira, M.; Altuzar, V.; Tomás, S. A.

    2003-01-01

    We report the effect of the addition of an epidermal growth factor to a Ricinus communis-based biopolymer in the healing of a rat tibia model. Bone repair and osteointegration after a period of three weeks were evaluated employing photoacoustic spectroscopy and x-ray diffraction. A parallel study was performed at 1, 2, 3, 4, 5, 6, 7, and 8 weeks with energy dispersive x-ray spectroscopy. We conclude that the use of an epidermal growth factor (group EGF) in vivo accelerates the process of bony repair in comparison with other groups, and that the employment of the Ricinus communis-based biopolymer as a bone substitute decreases bone production.

  13. Recurrence of amblyopia after occlusion therapy.

    PubMed

    Bhola, Rahul; Keech, Ronald V; Kutschke, Pamela; Pfeifer, Wanda; Scott, William E

    2006-11-01

    To determine the stability of visual acuity (VA) after a standardized occlusion regimen in children with strabismic and/or anisometropic amblyopia. Retrospective, population-based, consecutive observational case series. Four hundred forty-nine patients younger than 10 years who underwent an occlusion trial for amblyopia and were observed until there was a recurrence of amblyopia or for a maximum of 1 year after decrease or cessation of occlusion therapy. We performed a retrospective chart review of all patients treated by occlusion therapy for strabismic and/or anisometropic amblyopia at our institution over a 34-year period. Of the 1621 patients identified in our database, 449 met the eligibility criteria and were included in this study. Patients having at least a 2 logarithm of the minimum angle of resolution (logMAR)-level improvement in VA by optotypes or a change from unmaintained to maintained fixation preference during the course of occlusion therapy were included. A recurrence of amblyopia was defined as > or =2 logMAR levels of VA reduction or reversal of fixation preference within 1 year after a decrease or cessation of occlusion therapy. Recurrence of amblyopia after a decrease or cessation of occlusion therapy and its relationship with patient age and VA of the amblyopic eye at the time of decrease or cessation of occlusion therapy. Of 653 occlusion trials, 179 (27%) resulted in recurrence of amblyopia. The recurrence was found to be inversely correlated with patient age. There was no statistically significant association between the recurrence of amblyopia and VA of the amblyopic eye at the end of maximal occlusion therapy. There is a clinically important risk of amblyopia recurrence when occlusion therapy is decreased before the age of 10 years. The risk of recurrence is inversely correlated with age (P<0.0001).

  14. Microarray analysis to identify the similarities and differences of pathogenesis between aortic occlusive disease and abdominal aortic aneurysm.

    PubMed

    Wang, Guofu; Bi, Lechang; Wang, Gaofeng; Huang, Feilai; Lu, Mingjing; Zhu, Kai

    2018-06-01

    Objectives Expression profile of GSE57691 was analyzed to identify the similarities and differences between aortic occlusive disease and abdominal aortic aneurysm. Methods The expression profile of GSE57691 was downloaded from Gene Expression Omnibus database, including 20 small abdominal aortic aneurysm samples, 29 large abdominal aortic aneurysm samples, 9 aortic occlusive disease samples, and 10 control samples. Using the limma package in R, the differentially expressed genes were screened. Followed by enrichment analysis was performed for the differentially expressed genes using database for annotation, visualization, and integrated discovery online tool. Based on string online tool and Cytoscape software, protein-protein interaction network and module analyses were carried out. Moreover, integrated TF platform database and Cytoscape software were used for constructing transcriptional regulatory networks. Results As a result, 1757, 354, and 396 differentially expressed genes separately were identified in aortic occlusive disease, large abdominal aortic aneurysm, and small abdominal aortic aneurysm samples. UBB was significantly enriched in proteolysis related pathways with a high degree in three groups. SPARCL1 was another gene shared by these groups and regulated by NFIA, which had a high degree in transcriptional regulatory network. ACTB, a significant upregulated gene in abdominal aortic aneurysm samples, could be regulated by CLIC4, which was significantly enriched in cell motions. ACLY and NFIB were separately identified in aortic occlusive disease and small abdominal aortic aneurysm samples, and separately enriched in lipid metabolism and negative regulation of cell proliferation. Conclusions The downregulated UBB, NFIA, and SPARCL1 might play key roles in both aortic occlusive disease and abdominal aortic aneurysm, while the upregulated ACTB might only involve in abdominal aortic aneurysm. ACLY and NFIB were specifically involved in aortic occlusive

  15. PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells.

    PubMed

    Llorens, Franc; Carulla, Patricia; Villa, Ana; Torres, Juan M; Fortes, Puri; Ferrer, Isidre; del Río, José A

    2013-10-01

    The prion protein (PrP) plays a key role in prion disease pathogenesis. Although the misfolded and pathologic variant of this protein (PrP(SC)) has been studied in depth, the physiological role of PrP(C) remains elusive and controversial. PrP(C) is a cell-surface glycoprotein involved in multiple cellular functions at the plasma membrane, where it interacts with a myriad of partners and regulates several intracellular signal transduction cascades. However, little is known about the gene expression changes modulated by PrP(C) in animals and in cellular models. In this article, we present PrP(C)-dependent gene expression signature in N2a cells and its implication in the most overrepresented functions: cell cycle, cell growth and proliferation, and maintenance of cell shape. PrP(C) over-expression enhances cell proliferation and cell cycle re-entrance after serum stimulation, while PrP(C) silencing slows down cell cycle progression. In addition, MAP kinase and protein kinase B (AKT) pathway activation are under the regulation of PrP(C) in asynchronous cells and following mitogenic stimulation. These effects are due in part to the modulation of epidermal growth factor receptor (EGFR) by PrP(C) in the plasma membrane, where the two proteins interact in a multimeric complex. We also describe how PrP(C) over-expression modulates filopodia formation by Rho GTPase regulation mainly in an AKT-Cdc42-N-WASP-dependent pathway. © 2013 International Society for Neurochemistry.

  16. The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation.

    PubMed

    Chung, Chaeuk; Yoo, Geon; Kim, Tackhoon; Lee, Dahye; Lee, Choong-Sik; Cha, Hye Rim; Park, Yeon Hee; Moon, Jae Young; Jung, Sung Soo; Kim, Ju Ock; Lee, Jae Cheol; Kim, Sun Young; Park, Hee Sun; Park, Myoungrin; Park, Dong Il; Lim, Dae-Sik; Jang, Kang Won; Lee, Jeong Eun

    2016-10-14

    Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIP's effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenograft's tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 expression and regulation in uterine leiomyoma.

    PubMed

    Marsh, Erica E; Chibber, Shani; Wu, Ju; Siegersma, Kendra; Kim, Julie; Bulun, Serdar

    2016-04-01

    To determine the presence, differential expression, and regulation of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in uterine leiomyomas. Laboratory in vivo and in vitro study with the use of human leiomyoma and myometrial tissue and primary cells. Academic medical center. Leiomyoma and myometrial tissue samples and cultured cells. 5-Aza-2'-deoxycytidine (5-aza-dC) treatment. Fold-change difference between EFEMP1 and fibulin-3 expression in leiomyoma tissue and cells compared with matched myometrial samples, and fold-change difference in EFEMP1 expression with 5-Aza-dC treatment. In vivo, EFEMP1 expression was 3.19-fold higher in myometrial tissue than in leiomyoma tissue. EFEMP1 expression in vitro was 5.03-fold higher in myometrial cells than in leiomyoma cells. Western blot and immunohistochemistry staining of tissue and cells confirmed similar findings in protein expression. Treatment of leiomyoma cells with 5-Aza-dC resulted in increased expression of EFEMP1 in vitro. The EFEMP1 gene and its protein product, fibulin-3, are both significantly down-regulated in leiomyoma compared with myometrium when studied both in vivo and in vitro. The increase in EFEMP1 expression in leiomyoma cells with 5-Aza-dC treatment suggest that differential methylation is responsible, in part, for the differences seen in gene expression. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response.

    PubMed

    Elentner, Andreas; Schmuth, Matthias; Yannoutsos, Nikolaos; Eichmann, Thomas O; Gruber, Robert; Radner, Franz P W; Hermann, Martin; Del Frari, Barbara; Dubrac, Sandrine

    2018-01-01

    The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. [Temporomandibular joint, occlusion and bruxism].

    PubMed

    Orthlieb, J D; Ré, J P; Jeany, M; Giraudeau, A

    2016-09-01

    Temporomandibular joint and dental occlusion are joined for better and worse. TMJ has its own weaknesses, sometimes indicated by bad functional habits and occlusal disorders. Occlusal analysis needs to be addressed simply and clearly. The term "malocclusion" is not reliable to build epidemiological studies, etiologic mechanisms or therapeutic advice on this "diagnosis". Understanding the impact of pathogenic malocclusion is not just about occlusal relationships that are more or less defective, it requires to locate them within the skeletal framework, the articular and behavioural context of the patient, and above all to assess their impact on the functions of the masticatory system. The TMJ-occlusion couple is often symbiotic, developing together in relation to its environment, compensating for its own shortcomings. However, a third partner may alter this relationship, such as bruxism, or more generally oral parafunctions, trauma or an interventionist practitioner. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. 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.

  1. Differential regulation of cellulose orientation at the inner and outer face of epidermal cells in the Arabidopsis hypocotyl.

    PubMed

    Crowell, Elizabeth Faris; Timpano, Hélène; Desprez, Thierry; Franssen-Verheijen, Tiny; Emons, Anne-Mie; Höfte, Herman; Vernhettes, Samantha

    2011-07-01

    It is generally believed that cell elongation is regulated by cortical microtubules, which guide the movement of cellulose synthase complexes as they secrete cellulose microfibrils into the periplasmic space. Transversely oriented microtubules are predicted to direct the deposition of a parallel array of microfibrils, thus generating a mechanically anisotropic cell wall that will favor elongation and prevent radial swelling. Thus far, support for this model has been most convincingly demonstrated in filamentous algae. We found that in etiolated Arabidopsis thaliana hypocotyls, microtubules and cellulose synthase trajectories are transversely oriented on the outer surface of the epidermis for only a short period during growth and that anisotropic growth continues after this transverse organization is lost. Our data support previous findings that the outer epidermal wall is polylamellate in structure, with little or no anisotropy. By contrast, we observed perfectly transverse microtubules and microfibrils at the inner face of the epidermis during all stages of cell expansion. Experimental perturbation of cortical microtubule organization preferentially at the inner face led to increased radial swelling. Our study highlights the previously underestimated complexity of cortical microtubule organization in the shoot epidermis and underscores a role for the inner tissues in the regulation of growth anisotropy.

  2. Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse

    PubMed Central

    Konger, Raymond L.; Derr-Yellin, Ethel; Travers, Jeffrey B.; Ocana, Jesus A.; Sahu, Ravi P.

    2017-01-01

    It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin. Interestingly, the increase in UVB-induced apoptosis in Pparg-/-epi mice is not accompanied by a change in cyclobutane pyrimidine dimer clearance or in mutation burden. This suggests that loss of epidermal PPARγ does not result in a significant alteration in DNA repair capacity. However, loss of epidermal PPARγ results in marked immunosuppression using a contact hypersensitivity (CHS) model. This impaired CHS response was significantly alleviated using neutralizing TNF-α antibodies or loss of germline Tnf. In addition, the PPARγ agonist rosiglitazone reversed UVB-induced systemic immunosuppression (UV-IS) as well as UV-induced growth of B16F10 melanoma tumor cells in syngeneic mice. Finally, increased B16F10 tumor growth was observed when injected subcutaneously into Pparg-/-epi mice. Thus, we provide novel evidence that epidermal PPARγ is important for cutaneous immune function and the acute photoresponse. PMID:29228682

  3. Stromal cell-derived factor 1 (SDF-1) accelerated skin wound healing by promoting the migration and proliferation of epidermal stem cells.

    PubMed

    Guo, Rui; Chai, Linlin; Chen, Liang; Chen, Wenguang; Ge, Liangpeng; Li, Xiaoge; Li, Hongli; Li, Shirong; Cao, Chuan

    2015-06-01

    Epidermal stem cells could contribute to skin repair through the migration of cells from the neighboring uninjured epidermis, infundibulum, hair follicle, or sebaceous gland. However, little is known about the factors responsible for the complex biological processes in wound healing. Herein, we will show that the attracting chemokine, SDF-1/CXCR4, is a major regulator involved in the migration of epidermal stem cells during wound repair. We found that the SDF-1 levels were markedly increased at the wound margins following injury and CXCR4 expressed in epidermal stem cells and proliferating epithelial cells. Blocking the SDF-1/CXCR4 axis resulted in a significant reduction in epidermal stem cell migration toward SDF-1 in vitro and delayed wound healing in vivo, while an SDF-1 treatment enhanced epidermal stem cell migration and proliferation and accelerated wound healing. These results provide direct evidence that SDF-1 promotes epidermal stem cell migration, accelerates skin regeneration, and makes the development of new regenerative therapeutic strategies for wound healing possible.

  4. Functions of Vγ4 T Cells and Dendritic Epidermal T Cells on Skin Wound Healing

    PubMed Central

    Li, Yashu; Wu, Jun; Luo, Gaoxing; He, Weifeng

    2018-01-01

    Wound healing is a complex and dynamic process that progresses through the distinct phases of hemostasis, inflammation, proliferation, and remodeling. Both inflammation and re-epithelialization, in which skin γδ T cells are heavily involved, are required for efficient skin wound healing. Dendritic epidermal T cells (DETCs), which reside in murine epidermis, are activated to secrete epidermal cell growth factors, such as IGF-1 and KGF-1/2, to promote re-epithelialization after skin injury. Epidermal IL-15 is not only required for DETC homeostasis in the intact epidermis but it also facilitates the activation and IGF-1 production of DETC after skin injury. Further, the epidermal expression of IL-15 and IGF-1 constitutes a feedback regulatory loop to promote wound repair. Dermis-resident Vγ4 T cells infiltrate into the epidermis at the wound edges through the CCR6-CCL20 pathway after skin injury and provide a major source of IL-17A, which enhances the production of IL-1β and IL-23 in the epidermis to form a positive feedback loop for the initiation and amplification of local inflammation at the early stages of wound healing. IL-1β and IL-23 suppress the production of IGF-1 by DETCs and, therefore, impede wound healing. A functional loop may exist among Vγ4 T cells, epidermal cells, and DETCs to regulate wound repair.

  5. Catheter Occlusion in Home Infusion: The Influence of Needleless Connector Design on Central Catheter Occlusion.

    PubMed

    Williams, Ann

    Thrombotic catheter occlusion is a common complication associated with central venous catheters (CVCs). A wide variety of needleless connectors that differ greatly in design and function are available for use with CVCs; however, there are a limited number of studies comparing the catheter occlusion rate associated with differently designed needleless connectors. This retrospective observational study compared occlusion rates associated with a split-septum neutral-displacement needleless connector versus those of a solid-surface neutral-reflux needleless connector in patients undergoing home infusion therapy. The neutral-reflux needleless connector was associated with a significant reduction in occlusion rate and thrombolytic use versus the neutral-displacement needleless connector.

  6. Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification.

    PubMed

    Murata, Teruasa; Honda, Tetsuya; Egawa, Gyohei; Yamamoto, Yasuo; Ichijo, Ryo; Toyoshima, Fumiko; Dainichi, Teruki; Kabashima, Kenji

    2018-04-26

    Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca 2+ ] i ) is one of the factors predicted to regulate cornification, the dynamics of [Ca 2+ ] i in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca 2+ ] i in mouse skin. [Ca 2+ ] i was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca 2+ ] i also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca 2+ ] i at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca 2+ ] i preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.

  7. Brassinosteroids control root epidermal cell fate via direct regulation of a MYB-bHLH-WD40 complex by GSK3-like kinases

    PubMed Central

    Cheng, Yinwei; Zhu, Wenjiao; Chen, Yuxiao; Ito, Shinsaku; Asami, Tadao; Wang, Xuelu

    2014-01-01

    In Arabidopsis, root hair and non-hair cell fates are determined by a MYB-bHLH-WD40 transcriptional complex and are regulated by many internal and environmental cues. Brassinosteroids play important roles in regulating root hair specification by unknown mechanisms. Here, we systematically examined root hair phenotypes in brassinosteroid-related mutants, and found that brassinosteroid signaling inhibits root hair formation through GSK3-like kinases or upstream components. We found that with enhanced brassinosteroid signaling, GL2, a cell fate marker for non-hair cells, is ectopically expressed in hair cells, while its expression in non-hair cells is suppressed when brassinosteroid signaling is reduced. Genetic analysis demonstrated that brassinosteroid-regulated root epidermal cell patterning is dependent on the WER-GL3/EGL3-TTG1 transcriptional complex. One of the GSK3-like kinases, BIN2, interacted with and phosphorylated EGL3, and EGL3s mutated at phosphorylation sites were retained in hair cell nuclei. BIN2 phosphorylated TTG1 to inhibit the activity of the WER-GL3/EGL3-TTG1 complex. Thus, our study provides insights into the mechanism of brassinosteroid regulation of root hair patterning. DOI: http://dx.doi.org/10.7554/eLife.02525.001 PMID:24771765

  8. 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.

  9. Antimicrobial peptides and pro-inflammatory cytokines are differentially regulated across epidermal layers following bacterial stimuli.

    PubMed

    Percoco, Giuseppe; Merle, Chloé; Jaouen, Thomas; Ramdani, Yasmina; Bénard, Magalie; Hillion, Mélanie; Mijouin, Lily; Lati, Elian; Feuilloley, Marc; Lefeuvre, Luc; Driouich, Azeddine; Follet-Gueye, Marie-Laure

    2013-12-01

    The skin is a natural barrier between the body and the environment and is colonised by a large number of microorganisms. Here, we report a complete analysis of the response of human skin explants to microbial stimuli. Using this ex vivo model, we analysed at both the gene and protein level the response of epidermal cells to Staphylococcus epidermidis (S. epidermidis) and Pseudomonas fluorescens (P. fluorescens), which are present in the cutaneous microbiota. We showed that both bacterial species affect the structure of skin explants without penetrating the living epidermis. We showed by real-time quantitative polymerase chain reaction (qPCR) that S. epidermidis and P. fluorescens increased the levels of transcripts that encode antimicrobial peptides (AMPs), including human β defensin (hBD)2 and hBD3, and the pro-inflammatory cytokines interleukin (IL)-1α and (IL)-1-β, as well as IL-6. In addition, we analysed the effects of bacterial stimuli on the expression profiles of genes related to innate immunity and the inflammatory response across the epidermal layers, using laser capture microdissection (LCM) coupled to qPCR. We showed that AMP transcripts were principally upregulated in suprabasal keratinocytes. Conversely, the expression of pro-inflammatory cytokines was upregulated in the lower epidermis. These findings were confirmed by protein localisation using specific antibodies coupled to optical or electron microscopy. This work underscores the potential value of further studies that use LCM on human skin explants model to study the roles and effects of the epidermal microbiota on human skin physiology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Selenoprotein W controls epidermal growth factor receptor surface expression, activation and degradation via receptor ubiquitination

    USDA-ARS?s Scientific Manuscript database

    Epidermal growth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of growth factor receptors that modulate a complex network of intracellular signaling pathways controlling growth, proliferation and differentiation. Selenoprotein W (SEPW1) is a diet-regulated, highly conserved...

  11. Epidermal growth factor receptor expression is related to post-mitotic events in cerebellar development: regulation by thyroid hormone.

    PubMed

    Carrasco, Emilce; Blum, Mariann; Weickert, Cynthia Shannon; Casper, Diana

    2003-01-10

    It has been established that thyroid hormone and neurotrophic factors both orchestrate developmental events in the brain. However, it is not clear how these two influences are related. In this study, we investigated the effects of thyroid hormone on cerebellar development and the coincident expression of transforming growth factor-alpha (TGF-alpha), a ligand in the epidermal growth factor (EGF) family, and the epidermal growth factor receptor (EGFR). Profiles of thyroid hormone expression were measured in postnatal animals and were found to peak at postnatal day 15 (P15). These levels dropped below detectable levels when mice were made hypothyroid with propylthiouracil (PTU). TGF-alpha and EGFR expression, as determined by RNAse protection assay, was maximal at P6 in normal animals, but remained low in hypothyroid animals, suggesting that thyroid hormone was responsible for their induction. In situ hybridization and immunohistochemical analysis of EGFR expression revealed that this receptor was present on granule cells within the inner zone of the external granule cell layer (EGL), suggesting that EGFR-ligands were not inducing granule cell proliferation. The persistence of EGFR expression on migrating granule cells and subsequent down-regulation of expression in the internal granule cell layer (IGL) implicates a role for EGFR-ligands in differentiation and/or migration. In hypothyroid animals, we observed a delayed progression of granule cell migration, consistent with the persistence of EGFR labeling in the EGL, and in the 'pile-up' of labeled cells at the interface between the molecular layer and the Purkinje cell layer. Taken together, these results implicate thyroid hormone in the coordinated expression of TGF-alpha and EGFR, which are positioned to play a role in post-mitotic developmental events in the cerebellum.

  12. 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.

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

    MedlinePlus

    ... Conditions Stevens-Johnson syndrome/toxic epidermal necrolysis Stevens-Johnson syndrome/toxic epidermal necrolysis Printable PDF Open All ... to view the expand/collapse boxes. Description Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a ...

  14. DEFECTIVE KERNEL1 (DEK1) Regulates Cell Walls in the Leaf Epidermis1

    PubMed Central

    Amanda, Dhika; Ingram, Gwyneth C.

    2016-01-01

    The plant epidermis is crucial to survival, regulating interactions with the environment and controlling plant growth. The phytocalpain DEFECTIVE KERNEL1 (DEK1) is a master regulator of epidermal differentiation and maintenance, acting upstream of epidermis-specific transcription factors, and is required for correct cell adhesion. It is currently unclear how changes in DEK1 lead to cellular defects in the epidermis and the pathways through which DEK1 acts. We have combined growth kinematic studies, cell wall analysis, and transcriptional analysis of genes downstream of DEK1 to determine the cause of phenotypic changes observed in DEK1-modulated lines of Arabidopsis (Arabidopsis thaliana). We reveal a novel role for DEK1 in the regulation of leaf epidermal cell wall structure. Lines with altered DEK1 activity have epidermis-specific changes in the thickness and polysaccharide composition of cell walls that likely underlie the loss of adhesion between epidermal cells in plants with reduced levels of DEK1 and changes in leaf shape and size in plants constitutively overexpressing the active CALPAIN domain of DEK1. Calpain-overexpressing plants also have increased levels of cellulose and pectins in epidermal cell walls, and this is correlated with the expression of several cell wall-related genes, linking transcriptional regulation downstream of DEK1 with cellular effects. These findings significantly advance our understanding of the role of the epidermal cell walls in growth regulation and establish a new role for DEK1 in pathways regulating epidermal cell wall deposition and remodeling. PMID:27756823

  15. αPIX Is a Trafficking Regulator that Balances Recycling and Degradation of the Epidermal Growth Factor Receptor

    PubMed Central

    Kortüm, Fanny; Harms, Frederike Leonie; Hennighausen, Natascha; Rosenberger, Georg

    2015-01-01

    Endosomal sorting is an essential control mechanism for signaling through the epidermal growth factor receptor (EGFR). We report here that the guanine nucleotide exchange factor αPIX, which modulates the activity of Rho-GTPases, is a potent bimodal regulator of EGFR trafficking. αPIX interacts with the E3 ubiquitin ligase c-Cbl, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation. We show that EGF stimulation induces αPIX::c-Cbl complex formation. Simultaneously, αPIX and c-Cbl protein levels decrease, which depends on both αPIX binding to c-Cbl and c-Cbl ubiquitin ligase activity. Through interaction αPIX sequesters c-Cbl from EGFR and this results in reduced EGFR ubiquitination and decreased EGFR degradation upon EGF treatment. However, quantitatively more decisive for cellular EGFR distribution than impaired EGFR degradation is a strong stimulating effect of αPIX on EGFR recycling to the cell surface. This function depends on the GIT binding domain of αPIX but not on interaction with c-Cbl or αPIX exchange activity. In summary, our data demonstrate a previously unappreciated function of αPIX as a strong promoter of EGFR recycling. We suggest that the novel recycling regulator αPIX and the degradation factor c-Cbl closely cooperate in the regulation of EGFR trafficking: uncomplexed αPIX and c-Cbl mediate a positive and a negative feedback on EGFR signaling, respectively; αPIX::c-Cbl complex formation, however, results in mutual inhibition, which may reflect a stable condition in the homeostasis of EGF-induced signal flow. PMID:26177020

  16. Arabidopsis TRANSPARENT TESTA GLABRA2 is directly regulated by R2R3 MYB transcription factors and is involved in regulation of GLABRA2 transcription in epidermal differentiation.

    PubMed

    Ishida, Tetsuya; Hattori, Sayoko; Sano, Ryosuke; Inoue, Kayoko; Shirano, Yumiko; Hayashi, Hiroaki; Shibata, Daisuke; Sato, Shusei; Kato, Tomohiko; Tabata, Satoshi; Okada, Kiyotaka; Wada, Takuji

    2007-08-01

    Arabidopsis thaliana TRANSPARENT TESTA GLABRA2 (TTG2) encodes a WRKY transcription factor and is expressed in young leaves, trichomes, seed coats, and root hairless cells. An examination of several trichome and root hair mutants indicates that MYB and bHLH genes regulate TTG2 expression. Two MYB binding sites in the TTG2 5' regulatory region act as cis regulatory elements and as direct targets of R2R3 MYB transcription factors such as WEREWOLF, GLABRA1, and TRANSPARENT TESTA2. Mutations in TTG2 cause phenotypic defects in trichome development and seed color pigmentation. Transgenic plants expressing a chimeric repressor version of the TTG2 protein (TTG2:SRDX) showed defects in trichome formation, anthocyanin accumulation, seed color pigmentation, and differentiation of root hairless cells. GLABRA2 (GL2) expression was markedly reduced in roots of ProTTG2:TTG2:SRDX transgenic plants, suggesting that TTG2 is involved in the regulation of GL2 expression, although GL2 expression in the ttg2 mutant was similar to that in the wild type. Our analysis suggests a new step in a regulatory cascade of epidermal differentiation, in which complexes containing R2R3 MYB and bHLH transcription factors regulate the expression of TTG2, which then regulates GL2 expression with complexes containing R2R3 MYB and bHLH in the differentiation of trichomes and root hairless cells.

  17. Inositol-C2-PAF down-regulates components of the antigen presentation machinery in a 2D-model of epidermal inflammation.

    PubMed

    Semini, Geo; Hildmann, Annette; Klein, Andreas; Lucka, Lothar; Schön, Margarete; Schön, Michael P; Shmanai, Vadim; Danker, Kerstin

    2014-02-01

    In cutaneous inflammatory diseases, such as psoriasis, atopic dermatitis and allergic contact dermatitis, skin-infiltrating T lymphocytes and dendritic cells modulate keratinocyte function via the secretion of pro-inflammatory cytokines. Keratinocytes then produce mediators that recruit and activate immune cells and amplify the inflammatory response. These pathophysiological tissue changes are caused by altered gene expression and the proliferation and maturation of dermal and epidermal cells. We recently demonstrated that the glycosidated phospholipid Ino-C2-PAF down-regulates a plethora of gene products associated with innate and acquired immune responses and inflammation in the HaCaT keratinocyte cell line. To further evaluate the influence of Ino-C2-PAF we established an in vitro 2D-model of epidermal inflammation. The induction of inflammation and the impact of Ino-C2-PAF were assessed in this system using a genome-wide microarray analysis. In addition, the expression of selected genes was validated using qRT-PCR and flow cytometry. Treatment of the keratinocytes with a mix of proinflammatory cytokines resulted in transcriptional effects on a variety of genes involved in cutaneous inflammation and immunity, while additional treatment with Ino-C2-PAF counteracted the induction of many of these genes. Remarkably, Ino-C2-PAF suppressed the expression of a group of targets that are implicated in antigen processing and presentation, including MHC molecules. Thus, it is conceivable that Ino-C2-PAF possess therapeutic potential for inflammatory skin disorders, such as psoriasis and allergic contact dermatitis. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

    PubMed

    Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

    2017-05-01

    High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

  19. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation

    PubMed Central

    Gaviglio, Angela L.; Knelson, Erik H.; Blobe, Gerard C.

    2017-01-01

    High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor–like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.—Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. PMID:28174207

  20. Differentiated epidermal cells regain the ability to regenerate a skin equivalent by increasing the level of β-catenin in the cells.

    PubMed

    Zhao, Zhili; Zhang, Cuiping; Fu, Xiaobing; Yang, Rongya; Peng, Chen; Gu, Tingmin; Sui, Zhifu; Wang, Congmin; Liu, Chang

    2012-01-01

    Epidermal stem cells are of major importance for skin regeneration and tissue engineering, but differentiated epidermal cells lost their proliferative capacity and are no longer able to regenerate a skin equivalent. Here, we investigated the role of β-catenin in regulating regenerative functions of differentiated epidermal cells. Lithium chloride and a highly specific glycogen synthase kinase (GSK)-3β inhibitor were applied to induce the expression of β-catenin in differentiated epidermal cells. After a 6-day induction, the large flat-shaped cells with a small nuclear-cytoplasmic ratio had changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. Phenotypic assays showed a remarkably higher expression of CK19, β(1)-integrin, Oct4 and Nanog in induced cells than in the control group (p < 0.01). In addition, the results of growth and functional investigations demonstrated that the induced epidermal cells exhibited a high colony-forming ability, a long-term proliferative potential and the ability to regenerate a skin equivalent, which were regarded as the most important features of epidermal stem cells. These results suggest that the activation of β-catenin favors the reversion or dedifferentiation of differentiated epidermal cells to an immature or a less differentiated state. This study may also offer a new approach to yield enough epidermal stem cells for skin regeneration and tissue engineering. Copyright © 2012 S. Karger AG, Basel.

  1. 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.

  2. Epidermal nevus syndrome and didymosis aplasticosebacea.

    PubMed

    Demerdjieva, Zdravka; Kavaklieva, Svetlana; Tsankov, Nikolay

    2007-01-01

    The epidermal nevus syndrome is a disease complex consisting of the association of an epidermal nevus with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular, and urogenital systems. The epidermal nevi are classified according to their predominant component; nevus sebaceus (sebaceous glands), nevus comedonicus (hair follicles), and nevus verrucosus (keratinocytes). We report a neonate who presented with a nevus sebaceus on the scalp and face as well as a coloboma and dermoid on his left eye. Within the sebaceous nevus on the scalp, circumscribed lesions of aplasia cutis congenita were detected, which is consistent with the recently proposed term in the literature didymosis aplasticosebacea.

  3. Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

    PubMed

    Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

    2009-02-01

    A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the

  4. Posttraumatic epidermal inclusion cyst of the deep infratemporal fossa.

    PubMed

    Acarturk, T O; Stofman, G M

    2001-01-01

    The authors report a case of an epidermal inclusion cyst found in the deep infratemporal fossa 12 years after the patient sustained blunt trauma to that region. Posttraumatic epidermal inclusion cysts are rare and occur mainly in the fingers, palms, and soles. Introduction of the epidermal elements into the dermis during the trauma is thought to be the cause. This case is rare in presentation, with few reports in the English literature that describe an epidermal inclusion cyst in the deep infratemporal fossa. Review of the English literature disclosed no other cases of epidermal inclusion cyst after blunt trauma involving the deep infratemporal region.

  5. Duox, Flotillin-2, and Src42A Are Required to Activate or Delimit the Spread of the Transcriptional Response to Epidermal Wounds in Drosophila

    PubMed Central

    Juarez, Michelle T.; Patterson, Rachel A.; Sandoval-Guillen, Efren; McGinnis, William

    2011-01-01

    The epidermis is the largest organ of the body for most animals, and the first line of defense against invading pathogens. A breach in the epidermal cell layer triggers a variety of localized responses that in favorable circumstances result in the repair of the wound. Many cellular and genetic responses must be limited to epidermal cells that are close to wounds, but how this is regulated is still poorly understood. The order and hierarchy of epidermal wound signaling factors are also still obscure. The Drosophila embryonic epidermis provides an excellent system to study genes that regulate wound healing processes. We have developed a variety of fluorescent reporters that provide a visible readout of wound-dependent transcriptional activation near epidermal wound sites. A large screen for mutants that alter the activity of these wound reporters has identified seven new genes required to activate or delimit wound-induced transcriptional responses to a narrow zone of cells surrounding wound sites. Among the genes required to delimit the spread of wound responses are Drosophila Flotillin-2 and Src42A, both of which are transcriptionally activated around wound sites. Flotillin-2 and constitutively active Src42A are also sufficient, when overexpressed at high levels, to inhibit wound-induced transcription in epidermal cells. One gene required to activate epidermal wound reporters encodes Dual oxidase, an enzyme that produces hydrogen peroxide. We also find that four biochemical treatments (a serine protease, a Src kinase inhibitor, methyl-ß-cyclodextrin, and hydrogen peroxide) are sufficient to globally activate epidermal wound response genes in Drosophila embryos. We explore the epistatic relationships among the factors that induce or delimit the spread of epidermal wound signals. Our results define new genetic functions that interact to instruct only a limited number of cells around puncture wounds to mount a transcriptional response, mediating local repair and

  6. CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness.

    PubMed

    Grass, G Daniel; Tolliver, Lauren B; Bratoeva, Momka; Toole, Bryan P

    2013-09-06

    The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777-788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.

  7. CD147, CD44, and the Epidermal Growth Factor Receptor (EGFR) Signaling Pathway Cooperate to Regulate Breast Epithelial Cell Invasiveness*

    PubMed Central

    Grass, G. Daniel; Tolliver, Lauren B.; Bratoeva, Momka; Toole, Bryan P.

    2013-01-01

    The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777–788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer. PMID:23888049

  8. The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities.

    PubMed

    Troy, Tammy-Claire; Turksen, Kursad

    2007-06-01

    Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune system. Using transgenic mouse technology, we have demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are intricately involved in cell signaling during epidermal differentiation and that an epidermal suprabasal overexpression of Cldn6 results in a perturbed epidermal terminal differentiation program with distinct phenotypic abnormalities. To delineate the role of the Cldn cytoplasmic tail domain in epidermal differentiation, we engineered transgenic mice targeting the overexpression of a Cldn6 cytoplasmic tail-truncation mutant in the epidermis. Transgenic mice were characterized by a lethal barrier dysfunction in addition to the existence of hyperproliferative squamous invaginations/cysts replacing hair follicles. Immunohistochemical analysis revealed an epidermal cytoplasmic accumulation of Cldn6, Cldn11, Cldn12, and Cldn18, downregulation of Cldn1 and aberrant expression of various classical markers of epidermal differentiation; namely the basal keratins as well as K1, involucrin, loricrin, and filaggrin. Collectively these studies suggest an important role for Cldns in epidermal/hair follicle differentiation programs likely involving cross talk to signaling pathways (e.g., Notch) directing cell fate selection and differentiation.

  9. Transcript Profiling Identifies Gene Cohorts Controlled by Each Signal Regulating Trans-Differentiation of Epidermal Cells of Vicia faba Cotyledons to a Transfer Cell Phenotype

    PubMed Central

    Zhang, Hui-Ming; Wheeler, Simon L.; Xia, Xue; Colyvas, Kim; Offler, Christina E.; Patrick, John W.

    2017-01-01

    Transfer cells (TCs) support high rates of membrane transport of nutrients conferred by a plasma membrane area amplified by lining a wall labyrinth comprised of an uniform wall layer (UWL) upon which intricate wall ingrowth (WI) papillae are deposited. A signal cascade of auxin, ethylene, extracellular hydrogen peroxide (H2O2) and cytosolic Ca2+ regulates wall labyrinth assembly. To identify gene cohorts regulated by each signal, a RNA- sequencing study was undertaken using Vicia faba cotyledons. When cotyledons are placed in culture, their adaxial epidermal cells spontaneously undergo trans-differentiation to epidermal TCs (ETCs). Expressed genes encoding proteins central to wall labyrinth formation (signaling, intracellular organization, cell wall) and TC function of nutrient transport were assembled. Transcriptional profiles identified 9,742 annotated ETC-specific differentially expressed genes (DEGs; Log2fold change > 1; FDR p ≤ 0.05) of which 1,371 belonged to signaling (50%), intracellular organization (27%), cell wall (15%) and nutrient transporters (9%) functional categories. Expression levels of 941 ETC-specific DEGs were found to be sensitive to the known signals regulating ETC trans-differentiation. Significantly, signals acting alone, or in various combinations, impacted similar numbers of ETC-specific DEGs across the four functional gene categories. Amongst the signals acting alone, H2O2 exerted most influence affecting expression levels of 56% of the ETC-specific DEGs followed by Ca2+ (21%), auxin (18%) and ethylene (5%). The dominance by H2O2 was evident across all functional categories, but became more attenuated once trans-differentiation transitioned into WI papillae formation. Amongst the eleven signal combinations, H2O2/Ca2+ elicited the greatest impact across all functional categories accounting for 20% of the ETC-specific DEG cohort. The relative influence of the other signals acting alone, or in various combinations, varied across the four

  10. Transcript Profiling Identifies Gene Cohorts Controlled by Each Signal Regulating Trans-Differentiation of Epidermal Cells of Vicia faba Cotyledons to a Transfer Cell Phenotype.

    PubMed

    Zhang, Hui-Ming; Wheeler, Simon L; Xia, Xue; Colyvas, Kim; Offler, Christina E; Patrick, John W

    2017-01-01

    Transfer cells (TCs) support high rates of membrane transport of nutrients conferred by a plasma membrane area amplified by lining a wall labyrinth comprised of an uniform wall layer (UWL) upon which intricate wall ingrowth (WI) papillae are deposited. A signal cascade of auxin, ethylene, extracellular hydrogen peroxide (H 2 O 2 ) and cytosolic Ca 2+ regulates wall labyrinth assembly. To identify gene cohorts regulated by each signal, a RNA- sequencing study was undertaken using Vicia faba cotyledons. When cotyledons are placed in culture, their adaxial epidermal cells spontaneously undergo trans -differentiation to epidermal TCs (ETCs). Expressed genes encoding proteins central to wall labyrinth formation (signaling, intracellular organization, cell wall) and TC function of nutrient transport were assembled. Transcriptional profiles identified 9,742 annotated ETC-specific differentially expressed genes (DEGs; Log 2 fold change > 1; FDR p ≤ 0.05) of which 1,371 belonged to signaling (50%), intracellular organization (27%), cell wall (15%) and nutrient transporters (9%) functional categories. Expression levels of 941 ETC-specific DEGs were found to be sensitive to the known signals regulating ETC trans -differentiation. Significantly, signals acting alone, or in various combinations, impacted similar numbers of ETC-specific DEGs across the four functional gene categories. Amongst the signals acting alone, H 2 O 2 exerted most influence affecting expression levels of 56% of the ETC-specific DEGs followed by Ca 2+ (21%), auxin (18%) and ethylene (5%). The dominance by H 2 O 2 was evident across all functional categories, but became more attenuated once trans -differentiation transitioned into WI papillae formation. Amongst the eleven signal combinations, H 2 O 2 /Ca 2+ elicited the greatest impact across all functional categories accounting for 20% of the ETC-specific DEG cohort. The relative influence of the other signals acting alone, or in various combinations

  11. Differential Regulation of Cellulose Orientation at the Inner and Outer Face of Epidermal Cells in the Arabidopsis Hypocotyl[W

    PubMed Central

    Crowell, Elizabeth Faris; Timpano, Hélène; Desprez, Thierry; Franssen-Verheijen, Tiny; Emons, Anne-Mie; Höfte, Herman; Vernhettes, Samantha

    2011-01-01

    It is generally believed that cell elongation is regulated by cortical microtubules, which guide the movement of cellulose synthase complexes as they secrete cellulose microfibrils into the periplasmic space. Transversely oriented microtubules are predicted to direct the deposition of a parallel array of microfibrils, thus generating a mechanically anisotropic cell wall that will favor elongation and prevent radial swelling. Thus far, support for this model has been most convincingly demonstrated in filamentous algae. We found that in etiolated Arabidopsis thaliana hypocotyls, microtubules and cellulose synthase trajectories are transversely oriented on the outer surface of the epidermis for only a short period during growth and that anisotropic growth continues after this transverse organization is lost. Our data support previous findings that the outer epidermal wall is polylamellate in structure, with little or no anisotropy. By contrast, we observed perfectly transverse microtubules and microfibrils at the inner face of the epidermis during all stages of cell expansion. Experimental perturbation of cortical microtubule organization preferentially at the inner face led to increased radial swelling. Our study highlights the previously underestimated complexity of cortical microtubule organization in the shoot epidermis and underscores a role for the inner tissues in the regulation of growth anisotropy. PMID:21742992

  12. Influence of the fast-processing technique on the number of the occlusal contacts and occlusal vertical dimension of complete dentures.

    PubMed

    Atashrazm, Parsa; Alavijeh, Leila Zamani; Afshar, Maryam Sadat Sadrzadeh

    2011-03-01

    Occlusal errors during acryl processing affect the retention and stability of complete dentures. The aim of the present study was to assess the influence of a short curing technique on the number of occlusal contacts and the occlusal vertical dimension (OVD) of complete dentures. Complete dentures were prepared. The number of occlusal contacts was recorded in centric relation (CR) using 60 µ articulation paper. The OVD was recorded with the waxed trial denture in place. Dentures were then invested and processed with compression molding and short cure water bath technique. The number of occlusal contacts was recorded again. The amount of pin opening was measured for all of the complete dentures on the articulator. Data were analyzed with paired t-test to determine the alterations. The mean number of occlusal contacts before and after processing was 10.9 ± 2.4 and 6.3 ± 3.1 respectively (4.7 ± 1.9 decrease; p < 0.001). A 2 mm mean increase in OVD was observed in 47.7% of the dentures with < 6 occlusal contact changes and 88.9% of the dentures with ≥ 6 occlusal contact changes (p < 0.003). A significant change in the number of occlusal contacts was associated with an OVD increased up to two times. The short curing technique seems to be related to the decreased occlusal contacts and increased OVD. CLINICAL SIGNIFICANCES: More time is needed to adjust the occlusal errors of this method, because it has a negative effect on the morphologic pattern of artificial teeth of complete dentures and thus should be used carefully.

  13. Arabidopsis TRANSPARENT TESTA GLABRA2 Is Directly Regulated by R2R3 MYB Transcription Factors and Is Involved in Regulation of GLABRA2 Transcription in Epidermal Differentiation[W

    PubMed Central

    Ishida, Tetsuya; Hattori, Sayoko; Sano, Ryosuke; Inoue, Kayoko; Shirano, Yumiko; Hayashi, Hiroaki; Shibata, Daisuke; Sato, Shusei; Kato, Tomohiko; Tabata, Satoshi; Okada, Kiyotaka; Wada, Takuji

    2007-01-01

    Arabidopsis thaliana TRANSPARENT TESTA GLABRA2 (TTG2) encodes a WRKY transcription factor and is expressed in young leaves, trichomes, seed coats, and root hairless cells. An examination of several trichome and root hair mutants indicates that MYB and bHLH genes regulate TTG2 expression. Two MYB binding sites in the TTG2 5′ regulatory region act as cis regulatory elements and as direct targets of R2R3 MYB transcription factors such as WEREWOLF, GLABRA1, and TRANSPARENT TESTA2. Mutations in TTG2 cause phenotypic defects in trichome development and seed color pigmentation. Transgenic plants expressing a chimeric repressor version of the TTG2 protein (TTG2:SRDX) showed defects in trichome formation, anthocyanin accumulation, seed color pigmentation, and differentiation of root hairless cells. GLABRA2 (GL2) expression was markedly reduced in roots of ProTTG2:TTG2:SRDX transgenic plants, suggesting that TTG2 is involved in the regulation of GL2 expression, although GL2 expression in the ttg2 mutant was similar to that in the wild type. Our analysis suggests a new step in a regulatory cascade of epidermal differentiation, in which complexes containing R2R3 MYB and bHLH transcription factors regulate the expression of TTG2, which then regulates GL2 expression with complexes containing R2R3 MYB and bHLH in the differentiation of trichomes and root hairless cells. PMID:17766401

  14. Application of photogrammetry for analysis of occlusal contacts.

    PubMed

    Shigeta, Yuko; Hirabayashi, Rio; Ikawa, Tomoko; Kihara, Takuya; Ando, Eriko; Hirai, Shinya; Fukushima, Shunji; Ogawa, Takumi

    2013-04-01

    The conventional 2D-analysis methods for occlusal contacts provided limited information on tooth morphology. This present study aims to detect 3D positional information of occlusal contacts from 2D-photos via photogrammetry. We propose an image processing solution for analysis of occlusal contacts and facets via the black silicone method and a photogrammetric technique. The occlusal facets were reconstructed from a 2D-photograph data-set of inter-occlusal records into a 3D image via photogrammetry. The configuration of the occlusal surface was reproduced with polygons. In addition, the textures of the occlusal contacts were mapped to each polygon. DIFFERENCE FROM CONVENTIONAL METHODS: Constructing occlusal facets with 3D polygons from 2D-photos with photogrammetry was a defining characteristic of this image processing technique. It allowed us to better observe findings of the black silicone method. Compared with conventional 3D analysis using a 3D scanner, our 3D models did not reproduce the detail of the anatomical configuration. However, by merging the findings of the inter-occlusal record, the deformation of mandible and the displacement of periodontal ligaments under occlusal force were reflected in our model. EFFECT OR PERFORMANCE: Through the use of polygons in the conversion of 2D images to 3D images, we were able to define the relation between the location and direction of the occlusal contacts and facets, which was difficult to detect via conventional methods. Through our method of making a 3D polygon model, the findings of inter-occlusal records which reflected the jaw/teeth behavior under occlusal force could be observed 3-dimensionally. Copyright © 2012 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  15. Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis

    PubMed Central

    Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

    2017-01-01

    Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways. PMID:28277539

  16. Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis.

    PubMed

    Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

    2017-03-09

    Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways.

  17. Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model

    PubMed Central

    Gim, Sang-A; Sung, Jin-Hee; Shah, Fawad-Ali; Kim, Myeong-Ok

    2013-01-01

    Ferulic acid, a component of the plants Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort, exerts a neuroprotective effect by regulating various signaling pathways. This study showed that ferulic acid treatment prevents the injury-induced increase of collapsin response mediator protein 2 (CRMP-2) in focal cerebral ischemia. Glycogen synthase kinase-3β (GSK-3β) regulates CRMP-2 function through phosphorylation of CRMP-2. Moreover, the pro-apoptotic activity of GSK-3β is inactivated by phosphorylation by Akt. This study investigated whether ferulic acid modulates the expression of CRMP-2 and its upstream targets, Akt and GSK-3β, in focal cerebral ischemia. Male rats were treated immediately with ferulic acid (100 mg/kg, i.v.) or vehicle after middle cerebral artery occlusion (MCAO), and then cerebral cortices were collected 24 hr after MCAO. MCAO resulted in decreased levels of phospho-Akt and phospho-GSK-3β, while ferulic acid treatment prevented the decrease in the levels of these proteins. Moreover, phospho-CRMP-2 and CRMP-2 levels increased during MCAO, whereas ferulic acid attenuated these injury-induced increases. These results demonstrate that ferulic acid regulates the Akt/GSK-3β/CRMP-2 signaling pathway in focal cerebral ischemic injury, thereby protecting against brain injury. PMID:23825478

  18. Occlusal wear and occlusal condition in a convenience sample of young adults.

    PubMed

    Van't Spijker, A; Kreulen, C M; Bronkhorst, E M; Creugers, N H J

    2015-01-01

    To study progression of tooth wear quantitatively in a convenient sample of young adults and to assess possible correlations with occlusal conditions. Twenty-eight dental students participated in a three-year follow up study on tooth wear. Visible wear facets on full arch gypsum casts were assessed using a flatbed scanner and measuring software. Regression analyses were used to assess possible associations between the registered occlusal conditions 'occlusal guidance scheme', 'vertical overbite', 'horizontal overbite', 'depth of sagittal curve', 'canine Angle class relation', 'history of orthodontic treatment', and 'self-reported grinding/clenching' (independent variables) and increase of wear facets (dependent variable). Mean increase in facet surface areas ranged from 1.2 mm2 (premolars, incisors) to 3.4 mm2 (molars); the relative increase ranged from 15% to 23%. Backward regression analysis showed no significant relation for 'group function', 'vertical overbite', 'depth of sagittal curve', 'history of orthodontic treatment' nor 'self-reported clenching. The final multiple linear regression model showed significant associations amongst 'anterior protected articulation' and 'horizontal overbite' and increase of facet surface areas. For all teeth combined, only 'anterior protected articulation' had a significant effect. 'Self reported grinding' did not have a significant effect (p>0.07). In this study 'anterior protected articulation' and 'horizontal overbite', were significantly associated with the progression of tooth wear. Self reported grinding was not significantly associated with progression of tooth wear. Occlusal conditions such as anterior protected articulation and horizontal overbite seem to have an effect on the progression of occlusal tooth wear in this convenient sample of young adults. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Selective Ablation of Ctip2/Bcl11b in Epidermal Keratinocytes Triggers Atopic Dermatitis-Like Skin Inflammatory Responses in Adult Mice

    PubMed Central

    Guha, Gunjan; Li, Shan; Kyrylkova, Kateryna; Kioussi, Chrissa; Leid, Mark; Ganguli-Indra, Gitali; Indra, Arup K.

    2012-01-01

    Background Ctip2 is crucial for epidermal homeostasis and protective barrier formation in developing mouse embryos. Selective ablation of Ctip2 in epidermis leads to increased transepidermal water loss (TEWL), impaired epidermal proliferation, terminal differentiation, as well as altered lipid composition during development. However, little is known about the role of Ctip2 in skin homeostasis in adult mice. Methodology/Principal Findings To study the role of Ctip2 in adult skin homeostasis, we utilized Ctip2ep−/− mouse model in which Ctip2 is selectively deleted in epidermal keratinocytes. Measurement of TEWL, followed by histological, immunohistochemical, and RT-qPCR analyses revealed an important role of Ctip2 in barrier maintenance and in regulating adult skin homeostasis. We demonstrated that keratinocytic ablation of Ctip2 leads to atopic dermatitis (AD)-like skin inflammation, characterized by alopecia, pruritus and scaling, as well as extensive infiltration of immune cells including T lymphocytes, mast cells, and eosinophils. We observed increased expression of T-helper 2 (Th2)-type cytokines and chemokines in the mutant skin, as well as systemic immune responses that share similarity with human AD patients. Furthermore, we discovered that thymic stromal lymphopoietin (TSLP) expression was significantly upregulated in the mutant epidermis as early as postnatal day 1 and ChIP assay revealed that TSLP is likely a direct transcriptional target of Ctip2 in epidermal keratinocytes. Conclusions/Significance Our data demonstrated a cell-autonomous role of Ctip2 in barrier maintenance and epidermal homeostasis in adult mice skin. We discovered a crucial non-cell autonomous role of keratinocytic Ctip2 in suppressing skin inflammatory responses by regulating the expression of Th2-type cytokines. It is likely that the epidermal hyperproliferation in the Ctip2-lacking epidermis may be secondary to the compensatory response of the adult epidermis that is defective in

  20. Detecting natural occlusion boundaries using local cues

    PubMed Central

    DiMattina, Christopher; Fox, Sean A.; Lewicki, Michael S.

    2012-01-01

    Occlusion boundaries and junctions provide important cues for inferring three-dimensional scene organization from two-dimensional images. Although several investigators in machine vision have developed algorithms for detecting occlusions and other edges in natural images, relatively few psychophysics or neurophysiology studies have investigated what features are used by the visual system to detect natural occlusions. In this study, we addressed this question using a psychophysical experiment where subjects discriminated image patches containing occlusions from patches containing surfaces. Image patches were drawn from a novel occlusion database containing labeled occlusion boundaries and textured surfaces in a variety of natural scenes. Consistent with related previous work, we found that relatively large image patches were needed to attain reliable performance, suggesting that human subjects integrate complex information over a large spatial region to detect natural occlusions. By defining machine observers using a set of previously studied features measured from natural occlusions and surfaces, we demonstrate that simple features defined at the spatial scale of the image patch are insufficient to account for human performance in the task. To define machine observers using a more biologically plausible multiscale feature set, we trained standard linear and neural network classifiers on the rectified outputs of a Gabor filter bank applied to the image patches. We found that simple linear classifiers could not match human performance, while a neural network classifier combining filter information across location and spatial scale compared well. These results demonstrate the importance of combining a variety of cues defined at multiple spatial scales for detecting natural occlusions. PMID:23255731

  1. Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate.

    PubMed

    Arwert, Esther N; Lal, Rohit; Quist, Sven; Rosewell, Ian; van Rooijen, Nico; Watt, Fiona M

    2010-11-16

    In mammalian epidermis, integrin expression is normally confined to the basal proliferative layer that contains stem cells. However, in epidermal hyperproliferative disorders and tumors, integrins are also expressed by suprabasal cells, with concomitant up-regulation of Erk mitogen-activated protein kinase (MAPK) signaling. In transgenic mice, expression of activated MAPK kinase 1 (MEK1) in the suprabasal, nondividing, differentiated cell layers (InvEE transgenics) results in epidermal hyperproliferation and skin inflammation. We now demonstrate that wounding induces benign tumors (papillomas and keratoacanthomas) in InvEE mice. By generating chimeras between InvEE mice and mice that lack the MEK1 transgene, we demonstrate that differentiating, nondividing cells that express MEK1 stimulate adjacent transgene-negative cells to divide and become incorporated into the tumor mass. Dexamethasone treatment inhibits tumor formation, suggesting that inflammation is involved. InvEE skin and tumors express high levels of IL1α; treatment with an IL1 receptor antagonist delays tumor onset and reduces incidence. Depletion of γδ T cells and macrophages also reduces tumor incidence. Because a hallmark of cancer is uncontrolled proliferation, it is widely assumed that tumors arise only from dividing cells. In contrast, our studies show that differentiated epidermal cells can initiate tumor formation without reacquiring the ability to divide and that they do so by triggering an inflammatory infiltrate.

  2. Toxic epidermal necrolysis successfully treated with etanercept.

    PubMed

    Gubinelli, Emanuela; Canzona, Flora; Tonanzi, Tiziano; Raskovic, Desanka; Didona, Biagio

    2009-03-01

    Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept.

  3. Occlusal adjustment using the bite plate-induced occlusal position as a reference position for temporomandibular disorders: a pilot study

    PubMed Central

    2010-01-01

    Background Many researchers have not accepted the use of occlusal treatments for temporomandibular disorders (TMDs). However, a recent report described a discrepancy between the habitual occlusal position (HOP) and the bite plate-induced occlusal position (BPOP) and discussed the relation of this discrepancy to TMD. Therefore, the treatment outcome of evidence-based occlusal adjustments using the bite plate-induced occlusal position (BPOP) as a muscular reference position should be evaluated in patients with TMD. Methods The BPOP was defined as the position at which a patient voluntarily closed his or her mouth while sitting in an upright posture after wearing an anterior flat bite plate for 5 minutes and then removing the plate. Twenty-one patients with TMDs underwent occlusal adjustment using the BPOP. The occlusal adjustments were continued until bilateral occlusal contacts were obtained in the BPOP. The treatment outcomes were evaluated using the subjective dysfunction index (SDI) and the Helkimo Clinical Dysfunction Index (CDI) before and after the occlusal adjustments; the changes in these two indices between the first examination and a one-year follow-up examination were then analyzed. In addition, the difference between the HOP and the BPOP was three-dimensionally measured before and after the treatment. Results The percentage of symptom-free patients after treatment was 86% according to the SDI and 76% according to the CDI. The changes in the two indices after treatment were significant (p < 0.001). The changes in the mean HOP-BPOP differences on the x-axis (mediolateral) and the y-axis (anteroposterior) were significant (p < 0.05), whereas the change on the z-axis (superoinferior) was not significant (p > 0.1). Conclusion Although the results of the present study should be confirmed in other studies, a randomized clinical trial examining occlusal adjustments using the BPOP as a reference position appears to be warranted. PMID:20346167

  4. Specific binding of Clostridium perfringens enterotoxin fragment to Claudin-b and modulation of zebrafish epidermal barrier.

    PubMed

    Zhang, Jingjing; Ni, Chen; Yang, Zhenguo; Piontek, Anna; Chen, Huapu; Wang, Sijie; Fan, Yiming; Qin, Zhihai; Piontek, Joerg

    2015-08-01

    Claudins (Cldn) are the major components of tight junctions (TJs) sealing the paracellular cleft in tissue barriers of various organs. Zebrafish Cldnb, the homolog of mammalian Cldn4, is expressed at epithelial cell-cell contacts and is important for regulating epidermal permeability. The bacterial toxin Clostridium perfringens enterotoxin (CPE) has been shown to bind to a subset of mammalian Cldns. In this study, we used the Cldn-binding C-terminal domain of CPE (194-319 amino acids, cCPE 194-319 ) to investigate its functional role in modulating zebrafish larval epidermal barriers. In vitro analyses show that cCPE 194-319 removed Cldn4 from epithelial cells and disrupted the monolayer tightness, which could be rescued by the removal of cCPE 194-319. Incubation of zebrafish larvae with cCPE 194-319 removed Cldnb specifically from the epidermal cell membrane. Dye diffusion analysis with 4-kDa fluorescent dextran indicated that the permeability of the epidermal barrier increased due to cCPE 194-319 incubation. Electron microscopic investigation revealed reversible loss of TJ integrity by Cldnb removal. Collectively, these results suggest that cCPE 194-319 could be used as a Cldnb modulator to transiently open the epidermal barrier in zebrafish. In addition, zebrafish might be used as an in vivo system to investigate the capability of cCPE to enhance drug delivery across tissue barriers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Stent Graft in Managing Juxta-Renal Aortoiliac Occlusion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prabhudesai, V., E-mail: v_prabhudesai@hotmail.com; Mitra, K.; West, D. J.

    2003-09-15

    Endovascular procedures are frequently used as an alternative to surgical bypass in aortic and iliac occlusion. Stents have revolutionized the scope of such endovascular procedures, but there are few reports of stents or stent grafts in occlusive juxta-renal aortic occlusion. We present a case where such occlusion was managed by use of a stent graft with successful outcome.

  6. 21 CFR 878.4020 - Occlusive wound dressing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Occlusive wound dressing. 878.4020 Section 878...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4020 Occlusive wound dressing. (a) Identification. An occlusive wound dressing is a nonresorbable, sterile or non-sterile device...

  7. 21 CFR 878.4020 - Occlusive wound dressing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Occlusive wound dressing. 878.4020 Section 878...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4020 Occlusive wound dressing. (a) Identification. An occlusive wound dressing is a nonresorbable, sterile or non-sterile device...

  8. Acute left main coronary artery occlusion

    PubMed Central

    Burgazli, K. Mehmet; Bilgin, Mehmet; Soydan, Nedim; Chasan, Ridvan; Erdogan, Ali

    2013-01-01

    The treatment of an acute left main coronary artery occlusion still poses a challenge. In this case report we present a 50-year-old patient with an acute occlusion of the left main artery. After a successful angioplasty without “stenting” due to the complexity of the stenosis the patient underwent a successful bypass surgery. We discuss the therapeutic options of acute left main occlusion regarding medical, interventional and surgical options. PMID:24353543

  9. Toxic epidermal necrolysis: a paradigm of critical illness

    PubMed Central

    Estrella-Alonso, Alfonso; Aramburu, José Antonio; González-Ruiz, Mercedes Yolanda; Cachafeiro, Lucía; Sánchez, Manuel Sánchez; Lorente, José A.

    2017-01-01

    Toxic epidermal necrolysis is an adverse immunological skin reaction secondary in most cases to the administration of a drug. Toxic epidermal necrolysis, Stevens-Johnson syndrome, and multiform exudative erythema are part of the same disease spectrum. The mortality rate from toxic epidermal necrolysis is approximately 30%. The pathophysiology of toxic epidermal necrolysis is similar in many respects to that of superficial skin burns. Mucosal involvement of the ocular and genital epithelium is associated with serious sequelae if the condition is not treated early. It is generally accepted that patients with toxic epidermal necrolysis are better treated in burn units, which are experienced in the management of patients with extensive skin loss. Treatment includes support, elimination, and coverage with biosynthetic derivatives of the skin in affected areas, treatment of mucosal involvement, and specific immunosuppressive treatment. Of the treatments tested, only immunoglobulin G and cyclosporin A are currently used in most centers, even though there is no solid evidence to recommend any specific treatment. The particular aspects of the treatment of this disease include the prevention of sequelae related to the formation of synechiae, eye care to prevent serious sequelae that can lead to blindness, and specific immunosuppressive treatment. Better knowledge of the management principles of toxic epidermal necrolysis will lead to better disease management, higher survival rates, and lower prevalence of sequelae. PMID:29340540

  10. Inheritance of Occlusal Topography: A Twin Study

    PubMed Central

    Su, C-Y.; Corby, P.M.; Elliot, M.A.; Studen-Pavlovich, D.A.; Ranalli, D.N.; Rosa, B.; Wessel, J.; Schork, N.J.; Hart, T.C.; Bretz, W.A.

    2011-01-01

    Aim This was to determine the relative contribution of genetic factors on the morphology of occlusal surfaces of mandibular primary first molars by employing the twin study model. Methods The occlusal morphology of mandibular primary first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12 dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three-dimensional (3D) scanner. To compare the similarity of occlusal morphology between twin sets, each twin pair of occlusal surfaces was superimposed to establish the best fit by using computerized least squared techniques. Heritability was computed using a variance component model, adjusted for age and gender. Results DZ pairs demonstrated a greater degree of occlusal morphology variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018 (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24) sample and were not statistically significant (p=0.2203). The transformed mean differences were not statistically significantly different (p=0.2203). Heritability estimates of occlusal surface areas for right and left mandibular primary first molars were 97.5% and 98.2% (p<0.0001), respectively. Conclusions Occlusal morphology of DZ twin pairs was more variable than that of MZ twin pairs. Heritability estimates revealed that genetic factors strongly influence occlusal morphology of mandibular primary first molars. PMID:18328234

  11. The expression of proinflammatory genes in epidermal keratinocytes is regulated by hydration status.

    PubMed

    Xu, Wei; Jia, Shengxian; Xie, Ping; Zhong, Aimei; Galiano, Robert D; Mustoe, Thomas A; Hong, Seok J

    2014-04-01

    Mucosal wounds heal more rapidly, exhibit less inflammation, and are associated with minimal scarring when compared with equivalent cutaneous wounds. We previously demonstrated that cutaneous epithelium exhibits an exaggerated response to injury compared with mucosal epithelium. We hypothesized that treatment of injured skin with a semiocclusive dressing preserves the hydration of the skin and results in a wound healing phenotype that more closely resembles that of mucosa. Here we explored whether changes in hydration status alter epidermal gene expression patterns in rabbit partial-thickness incisional wounds. Using microarray studies on injured epidermis, we showed that global gene expression patterns in highly occluded versus non-occluded wounds are distinct. Many genes including IL-1β, IL-8, TNF-α (tumor necrosis factor-α), and COX-2 (cyclooxygenase 2) are upregulated in non-occluded wounds compared with highly occluded wounds. In addition, decreased levels of hydration resulted in an increased expression of proinflammatory genes in human ex vivo skin culture (HESC) and stratified keratinocytes. Hierarchical analysis of genes using RNA interference showed that both TNF-α and IL-1β regulate the expression of IL-8 through independent pathways in response to reduced hydration. Furthermore, both gene knockdown and pharmacological inhibition studies showed that COX-2 mediates the TNF-α/IL-8 pathway by increasing the production of prostaglandin E2 (PGE2). IL-8 in turn controls the production of matrix metalloproteinase-9 in keratinocytes. Our data show that hydration status directly affects the expression of inflammatory signaling in the epidermis. The identification of genes involved in the epithelial hydration pathway provides an opportunity to develop strategies to reduce scarring and optimize wound healing.

  12. Neuromuscular dentistry: Occlusal diseases and posture.

    PubMed

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture.

  13. Epidermal Micromorphology and Mesophyll Structure of Populus euphratica Heteromorphic Leaves at Different Development Stages

    PubMed Central

    Liu, Yubing; Li, Xinrong; Chen, Guoxiong; Li, Mengmeng; Liu, Meiling; Liu, Dan

    2015-01-01

    Leaf epidermal micromorphology and mesophyll structure during the development of Populus euphratica heteromorphic leaves, including linear, lanceolate, ovate, dentate ovate, dentate rhombic, dentate broad-ovate and dentate fan-shaped leaves, were studied by using electron and light microscopy. During development of heteromorphic leaves, epidermal appendages (wax crystals and trichomes) and special cells (mucilage cells and crystal idioblasts) increased in all leaf types while chloroplast ultrastructure and stomatal characters show maximum photosynthetic activity in dentate ovate and rhombic leaves. Also, functional analysis by subordinate function values shows that the maximum adaptability to adverse stress was exhibited in the broad type of mature leaves. The 12 heteromorphic leaf types are classified into three major groups by hierarchical cluster analysis: young, developing and mature leaves. Mature leaves can effectively obtain the highest stress resistance by combining the protection of xerophytic anatomy from drought stress, regulation of water uptake in micro-environment by mucilage and crystal idioblasts, and assistant defense of transpiration reduction through leaf epidermal appendages, which improves photosynthetic activity under arid desert conditions. Our data confirms that the main leaf function is differentiated during the developing process of heteromorphic leaves. PMID:26356300

  14. Epidermal Micromorphology and Mesophyll Structure of Populus euphratica Heteromorphic Leaves at Different Development Stages.

    PubMed

    Liu, Yubing; Li, Xinrong; Chen, Guoxiong; Li, Mengmeng; Liu, Meiling; Liu, Dan

    2015-01-01

    Leaf epidermal micromorphology and mesophyll structure during the development of Populus euphratica heteromorphic leaves, including linear, lanceolate, ovate, dentate ovate, dentate rhombic, dentate broad-ovate and dentate fan-shaped leaves, were studied by using electron and light microscopy. During development of heteromorphic leaves, epidermal appendages (wax crystals and trichomes) and special cells (mucilage cells and crystal idioblasts) increased in all leaf types while chloroplast ultrastructure and stomatal characters show maximum photosynthetic activity in dentate ovate and rhombic leaves. Also, functional analysis by subordinate function values shows that the maximum adaptability to adverse stress was exhibited in the broad type of mature leaves. The 12 heteromorphic leaf types are classified into three major groups by hierarchical cluster analysis: young, developing and mature leaves. Mature leaves can effectively obtain the highest stress resistance by combining the protection of xerophytic anatomy from drought stress, regulation of water uptake in micro-environment by mucilage and crystal idioblasts, and assistant defense of transpiration reduction through leaf epidermal appendages, which improves photosynthetic activity under arid desert conditions. Our data confirms that the main leaf function is differentiated during the developing process of heteromorphic leaves.

  15. Two Cases of Giant Epidermal Cyst Occurring in the Neck

    PubMed Central

    Kang, Sang-Gue; Kim, Chul-Han; Cho, Hong-Ki; Park, Mi-Youn; Lee, Yoon-Jin

    2011-01-01

    Epidermal cysts are the most common cysts of the skin. Aconventional epidermal cyst rarely reaches a size of more than 5 cm in diameter. We report on two cases of giant epidermal cyst occurring in the neck. One patient had a cyst measuring 12×9×9 cm and the other patient had a non-pulsatile, dome-shaped lesion in the neck, which measured 6×5×3 cm. The lesions were totally excised. Histopathologically, both were confirmed as giant epidermal cysts. PMID:22028561

  16. Biomechanics of occlusion--implications for oral rehabilitation.

    PubMed

    Peck, C C

    2016-03-01

    The dental occlusion is an important aspect of clinical dentistry; there are diverse functional demands ranging from highly precise tooth contacts to large crushing forces. Further, there are dogmatic, passionate and often diverging views on the relationship between the dental occlusion and various diseases and disorders including temporomandibular disorders, non-carious cervical lesions and tooth movement. This study provides an overview of the biomechanics of the masticatory system in the context of the dental occlusion's role in function. It explores the adaptation and precision of dental occlusion, its role in bite force, jaw movement, masticatory performance and its influence on the oro-facial musculoskeletal system. Biomechanics helps us better understand the structure and function of biological systems and consequently an understanding of the forces on, and displacements of, the dental occlusion. Biomechanics provides insight into the relationships between the dentition, jaws, temporomandibular joints, and muscles. Direct measurements of tooth contacts and forces are difficult, and biomechanical models have been developed to better understand the relationship between the occlusion and function. Importantly, biomechanical research will provide knowledge to help correct clinical misperceptions and inform better patient care. The masticatory system demonstrates a remarkable ability to adapt to a changing biomechanical environment and changes to the dental occlusion or other components of the musculoskeletal system tend to be well tolerated. © 2015 John Wiley & Sons Ltd.

  17. Dental occlusion and temporomandibular disorders.

    PubMed

    Stone, J Caitlin; Hannah, Andrew; Nagar, Nathan

    2017-10-27

    Data sourcesMedline, Scopus and Google Scholar.Study selectionTwo reviewers selected studies independently. English language clinical studies assessing the association between temporomandibular disorders (TMD) and features of dental occlusion were considered.Data extraction and synthesisStudy quality was assessed based on the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was presented.ResultsIn all 25 studies (17 case-control, eight comparative) were included. Overall there was a high variability between occlusal features and TMD diagnosis. Findings were consistent with a lack of clinically relevant association between TMD and dental occlusion. Only two studies were associated with TMD in the majority (≥50%) of single variable analyses in patient populations. Only mediotrusive interferences are associated with TMD in the majority of multiple variable analyses.ConclusionsThe findings support the absence of a disease-specific association, there is no ground to hypothesise a major role for dental occlusion in the pathophysiology of TMDs. Dental clinicians are thus encouraged to move forward and abandon the old-fashioned gnathological paradig.

  18. Conventional occlusion versus pharmacologic penalization for amblyopia.

    PubMed

    Li, Tianjing; Shotton, Kate

    2009-10-07

    Amblyopia is defined as defective visual acuity in one or both eyes without demonstrable abnormality of the visual pathway, and is not immediately resolved by wearing glasses. To assess the effectiveness and safety of conventional occlusion versus atropine penalization for amblyopia. We searched CENTRAL, MEDLINE, EMBASE, LILACS, the WHO International Clinical Trials Registry Platform, preference lists, science citation index and ongoing trials up to June 2009. We included randomized/quasi-randomized controlled trials comparing conventional occlusion to atropine penalization for amblyopia. Two authors independently screened abstracts and full text articles, abstracted data, and assessed the risk of bias. Three trials with a total of 525 amblyopic eyes were included. One trial was assessed as having a low risk of bias among these three trials, and one was assessed as having a high risk of bias.Evidence from three trials suggests atropine penalization is as effective as conventional occlusion. One trial found similar improvement in vision at six and 24 months. At six months, visual acuity in the amblyopic eye improved from baseline 3.16 lines in the occlusion and 2.84 lines in the atropine group (mean difference 0.034 logMAR; 95% confidence interval (CI) 0.005 to 0.064 logMAR). At 24 months, additional improvement was seen in both groups; but there continued to be no meaningful difference (mean difference 0.01 logMAR; 95% CI -0.02 to 0.04 logMAR). The second trial reported atropine to be more effective than occlusion. At six months, visual acuity improved 1.8 lines in the patching group and 3.4 lines in the atropine penalization group, and was in favor of atropine (mean difference -0.16 logMAR; 95% CI -0.23 to -0.09 logMAR). Different occlusion modalities were used in these two trials. The third trial had inherent methodological flaws and limited inference could be drawn.No difference in ocular alignment, stereo acuity and sound eye visual acuity between occlusion and

  19. Necrotizing Fasciitis of the Periorbital Region Complicated by Combined Central Retinal Artery Occlusion, Central Retinal Vein Occlusion, and Posterior Ciliary Occlusion.

    PubMed

    Sultan, Harris; Malik, Amina; Li, Helen K; Chévez-Barrios, Patricia; Lee, Andrew G

    A 50 year-old man on immunosuppressive agents presented with left eye vision loss, periorbital swelling, pain, and ophthalmoplegia. The patient was clinically found to have a central retinal artery and vein occlusion. A CT scan was performed which demonstrated intraorbital fat stranding, however the patient lacked sinus disease. The etiology of the orbital infection was held in question. The area was debrided in the operating room, and the specimen demonstrated group A streptococcal species consistent with necrotizing fasciitis. Periorbital necrotizing fasciitis should be suspected in patients with rapidly progressive orbital symptoms without sinus disease as lack of surgical intervention can result in poor outcomes. The unusual aspect to this case is the mechanism of vision loss, as the authors hypothesize that there was vascular infiltration of the infection resulting in the central retinal artery occlusion and central retinal vein occlusion which have not been previously reported secondary to necrotizing fasciitis of the orbit.

  20. Neuromuscular dentistry: Occlusal diseases and posture

    PubMed Central

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K.

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture. PMID:25737904

  1. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Tissue kallikrein induces SH-SY5Y cell proliferation via epidermal growth factor receptor and extracellular signal-regulated kinase1/2 pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, Zhengyu; Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437; Yang, Qi

    2014-03-28

    Highlights: • TK promotes EGFR phosphorylation in SH-SY5Y cells. • TK activates ERK1/2 and p38 phosphorylation in SH-SY5Y cells. • TK mediates SH-SY5Y cell proliferation via EGFR and ERK1/2 pathway. - Abstract: Tissue kallikrein (TK) is well known to take most of its biological functions through bradykinin receptors. In the present study, we found a novel signaling pathway mediated by TK through epidermal growth factor receptor (EGFR) in human SH-SY5Y cells. We discovered that TK facilitated the activation of EGFR, extracellular signal-regulated kinase (ERK) 1/2 and p38 cascade. Interestingly, not p38 but ERK1/2 phosphorylation was severely compromised in cells depletedmore » of EGFR. Nevertheless, impairment of signaling of ERK1/2 seemed not to be restricted to EGFR phosphorylation. We also observed that TK stimulation could induce SH-SY5Y cell proliferation, which was reduced by EGFR down-regulation or ERK1/2 inhibitor. Overall, our findings provided convincing evidence that TK could mediate cell proliferation via EGFR and ERK1/2 pathway in vitro.« less

  3. Matrix metalloproteinases and epidermal wound repair.

    PubMed

    Martins, Vera L; Caley, Matthew; O'Toole, Edel A

    2013-02-01

    Epidermal wound healing is a complex and highly coordinated process where several different cell types and molecules, such as growth factors and extracellular matrix (ECM) components, play an important role. Among the many proteins that are essential for the restoration of tissue integrity is the metalloproteinase (MMP) family. MMPs can act on ECM and non-ECM components affecting degradation and modulation of the ECM, growth-factor activation and cell-cell and cell-matrix signalling. MMPs are secreted by different cell types such as keratinocytes, fibroblasts and inflammatory cells at different stages and locations during wound healing, thereby regulating this process in a very coordinated and controlled way. In this article, we review the role of MMPs and their inhibitors (TIMPs), as well as the disintegrin and metalloproteinase with the thrombospondin motifs (ADAMs) family, in epithelial wound repair.

  4. Epidermal growth factor in alkali-burned corneal epithelial wound healing.

    PubMed

    Singh, G; Foster, C S

    1987-06-15

    We conducted a double-masked study to evaluate the effect of epidermal growth factor on epithelial wound healing and recurrent erosions in alkali-burned rabbit corneas. Epithelial wounds 10 mm in diameter healed completely under the influence of topical epidermal growth factor, whereas the control corneas did not resurface in the center. On reversal of treatment, the previously nonhealing epithelial defects healed when treated with topical epidermal growth factor eyedrops. Conversely, the epidermal growth factor-treated and resurfaced corneas developed epithelial defects when treatment was discontinued. Histopathologic examination disclosed hyperplastic epithelium growing over the damaged stroma laden with polymorphonuclear leukocytes when treated with epidermal growth factor eyedrops, but it did not adhere to the underlying tissue. Hydropic changes were seen intracellularly as well as between the epithelial cells and the stroma.

  5. 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. Copyright © 2013 Wiley Periodicals, Inc.

  6. Intracellular processing of epidermal growth factor. I. Acidification of 125I-epidermal growth factor in intracellular organelles.

    PubMed

    Matrisian, L M; Planck, S R; Magun, B E

    1984-03-10

    We previously reported that 125I-labeled epidermal growth factor is processed intracellularly to acidic macromolecules in Rat-1 fibroblasts. The present study defines the precursor-product relationship and localization of the processing steps to subcellular organelles by the use of a single isoelectric species of 125I-epidermal growth factor and Percoll gradient fractionation. The native pI 4.55 125I-epidermal growth factor was rapidly processed to a pI 4.2 species on or near the cell surface and in organelles corresponding to clathrin-coated vesicles, Golgi, and endoplasmic reticulum. This species was then processed to a pI 4.35 species in similar organelles. The pI 4.2 and 4.35 species were converted to a pI 4.0 species in dense, lysosome-like organelles. This species was ultimately degraded and exocytosed from the cell as low molecular weight products.

  7. The role of "rescue saccades" in tracking objects through occlusions.

    PubMed

    Zelinsky, Gregory J; Todor, Andrei

    2010-12-29

    We hypothesize that our ability to track objects through occlusions is mediated by timely assistance from gaze in the form of "rescue saccades"-eye movements to tracked objects that are in danger of being lost due to impending occlusion. Observers tracked 2-4 target sharks (out of 9) for 20 s as they swam through a rendered 3D underwater scene. Targets were either allowed to enter into occlusions (occlusion trials) or not (no occlusion trials). Tracking accuracy with 2-3 targets was ≥ 92% regardless of target occlusion but dropped to 74% on occlusion trials with four targets (no occlusion trials remained accurate; 83%). This pattern was mirrored in the frequency of rescue saccades. Rescue saccades accompanied approximatlely 50% of the Track 2-3 target occlusions, but only 34% of the Track 4 occlusions. Their frequency also decreased with increasing distance between a target and the nearest other object, suggesting that it is the potential for target confusion that summons a rescue saccade, not occlusion itself. These findings provide evidence for a tracking system that monitors for events that might cause track loss (e.g., occlusions) and requests help from the oculomotor system to resolve these momentary crises. As the number of crises increase with the number of targets, some requests for help go unsatisfied, resulting in degraded tracking.

  8. A case of epidermal cyst with pilomatrical differentiation.

    PubMed

    Ikoma, Norihiro; Iwashita, Kenichi; Umezawa, Yoshinori; Matsuyama, Takashi; Ohta, Yukinori; Ozawa, Akira; Umemura, Shinobu; Ueyama, Yoshito; Yamazaki, Hitoshi

    2004-09-01

    A 20-year-old Japanese woman with an epidermal cyst on the back is described. Physical examination revealed a deep blue and round shaped cystic lesion measuring 10 min in diameter. A comedo-like keratotic plug also could be seen at the center. Histologically, the inner surface of the cyst was clearly separated of two types of the cells. The one was layers of epidermal keratinocytes and the other looked like a basal layer of epidermis, which immunohistochemically stained by S-100, HMB-45, cytokeratin (CK19) and Fontana-Masson staining. We diagnosed this case as epidermal cyst with pilomatrical differentiation.

  9. Epidermal lipid in several cetacean species: ultrastructural observations.

    PubMed

    Pfeiffer, C J; Jones, F M

    1993-09-01

    The ultrastructure of the skin of four cetacean species, bottlenose dolphin (Tursiops truncatus) long-finned pilot whale (Globicephala melaena), humpback whale (Megaptera novaeangliae), and fin whale (Balaenoptera physalus) was investigated with particular reference to epidermal lipid. It has already been established that massive lipid reservoirs exist in whales, that the biochemical structures of cetacean lipids are unique, and that unusual intracellular lipid droplets appear in the epidermis. We report here some novel findings on scanning electron microscopic morphology of epidermal lipid, and on its ultrastructural morphology in general and specialized integumentary sites, including species not previously investigated. The intracellular epidermal lipid droplets were more extensive than lamellar body-derived intercellular lipid which is within the interstices of stratum externum cells. The intracellular droplets were spherical, highly variable in size ranging from 0.24 micron to 3.0 microns in diameter, appeared singly or were aggregated in cytoplasmic cavitations, and often were closely associated with epidermal cell nuclei. Evidence for exocytosis of the intracellular droplets was not observed. Significant numbers of intracellular lipid droplets are not observed in the epidermis of terrestrial mammals, so their presence is one of several aquatic specializations of the cetacean integument. Its full significance remains obscure, but it is more probably associated with epidermal cell metabolism than with secretion of lipid.

  10. The NADPH Oxidases DUOX1 and NOX2 Play Distinct Roles in Redox Regulation of Epidermal Growth Factor Receptor Signaling.

    PubMed

    Heppner, David E; Hristova, Milena; Dustin, Christopher M; Danyal, Karamatullah; Habibovic, Aida; van der Vliet, Albert

    2016-10-28

    The epidermal growth factor receptor (EGFR) plays a critical role in regulating airway epithelial homeostasis and responses to injury. Activation of EGFR is regulated by redox-dependent processes involving reversible cysteine oxidation by reactive oxygen species (ROS) and involves both ligand-dependent and -independent mechanisms, but the precise source(s) of ROS and the molecular mechanisms that control tyrosine kinase activity are incompletely understood. Here, we demonstrate that stimulation of EGFR activation by ATP in airway epithelial cells is closely associated with dynamic reversible oxidation of cysteine residues via sequential sulfenylation and S-glutathionylation within EGFR and the non-receptor-tyrosine kinase Src. Moreover, the intrinsic kinase activity of recombinant Src or EGFR was in both cases enhanced by H 2 O 2 but not by GSSG, indicating that the intermediate sulfenylation is the activating modification. H 2 O 2 -induced increase in EGFR tyrosine kinase activity was not observed with the C797S variant, confirming Cys-797 as the redox-sensitive cysteine residue that regulates kinase activity. Redox-dependent regulation of EGFR activation in airway epithelial cells was found to strongly depend on activation of either the NADPH oxidase DUOX1 or the homolog NOX2, depending on the activation mechanism. Whereas DUOX1 and Src play a primary role in EGFR transactivation by wound-derived signals such as ATP, direct ligand-dependent EGFR activation primarily involves NOX2 with a secondary role for DUOX1 and Src. Collectively, our findings establish that redox-dependent EGFR kinase activation involves a dynamic and reversible cysteine oxidation mechanism and that this activation mechanism variably involves DUOX1 and NOX2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Dermal Blimp1 Acts Downstream of Epidermal TGFβ and Wnt/β-Catenin to Regulate Hair Follicle Formation and Growth.

    PubMed

    Telerman, Stephanie B; Rognoni, Emanuel; Sequeira, Inês; Pisco, Angela Oliveira; Lichtenberger, Beate M; Culley, Oliver J; Viswanathan, Priyalakshmi; Driskell, Ryan R; Watt, Fiona M

    2017-11-01

    B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although in the epidermis Blimp1 is important for keratinocyte and sebocyte differentiation, its role in dermal fibroblasts is unclear. Here we show that Blimp1 is dynamically regulated in dermal papilla cells during hair follicle (HF) morphogenesis and the postnatal hair cycle, preceding dermal Wnt/β-catenin activation. Blimp1 ablation in E12.5 mouse dermal fibroblasts delayed HF morphogenesis and growth and prevented new HF formation after wounding. By combining targeted quantitative PCR screens with bioinformatic analysis and experimental validation we demonstrated that Blimp1 is both a target and a mediator of key dermal papilla inductive signaling pathways including transforming growth factor-β and Wnt/β-catenin. Epidermal overexpression of stabilized β-catenin was able to override the HF defects in Blimp1 mutant mice, underlining the close reciprocal relationship between the dermal papilla and adjacent HF epithelial cells. Overall, our study reveals the functional role of Blimp1 in promoting the dermal papilla inductive signaling cascade that initiates HF growth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Vascular occlusion with a balloon-expandable stent occluder.

    PubMed

    Moss, J G; Laborde, J C; Clem, M C; Rivera, F J; Encarnacion, C E; Meyer, K B; Palmaz, J C

    1994-05-01

    To evaluate the effectiveness of a new vascular occlusion device. The device was created by coating a balloon-expandable stent with a silicone sleeve that tapers to a blind-ended nozzle at its leading end. Once crimp-mounted on an angioplasty balloon catheter, the device is introduced over a guide wire through a small end hole in the nozzle. The device was tested for stability and occlusive ability. No migration was measured over a pulsatile pulse range of 50-300 mm Hg, and mean flow rate in the occluded vessel was reduced from 443 mL/min +/- 99 (standard deviation) to 1.9 mL/min +/- 2.7. Subsequently, 12 arteries were occluded in three dogs, and immediate vascular occlusion was achieved in all vessels. An arteriovenous fistula was created in another six dogs and was successfully occluded with the device. Follow-up arteriography at 3 months demonstrated persistent occlusion with no migration of the device. This new occlusive device offers immediate vascular occlusion with excellent stability.

  13. A New Occlusion Device: Application of the ArtVentive Endoluminal Occlusion System (EOS)—First in Human Clinical Trial

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Venbrux, Anthony C., E-mail: avenbrux@mfa.gwu.edu; Rudakov, Leon, E-mail: leonrudakov@artventivemedical.com; Plass, Andre, E-mail: andre.plass@usz.ch

    2013-05-24

    PurposeThe purpose of this study was to determine the safety and efficacy of a new endoluminal occlusion device, ArtVentive endoluminal occlusion system (EOS), to occlude the spermatic vein in symptomatic males with varicoceles.MethodsThe ArtVentive EOS device has been developed for percutaneous, peripheral occlusion of the peripheral arterial and venous vasculature. The system is comprised of an implantable occlusion device and a delivery catheter. At present, there are two device sizes: (a) size 1 for target vessels ranging between 3.5 and 5.5 mm in diameter, and (b) size 2 for target vessels 5.5–8.5 mm in diameter. The treatment group included six adult males,more » ages 22–34 years. Nine target vessels were occluded. A total of 20 devices were implanted in six subjects.ResultsThe acute occlusion rate at the end of the procedure was 100 % occurring in nine of nine vessels. The spermatic veins of all patients remained occluded on venography at 30 days follow-up. Pain scores related to varicoceles decreased in five of six patients.ConclusionsAlthough we recognize this study is limited, initial experience indicates that the ArtVentive EOS is a safe and effective new device for occlusion of vessels (varicoceles). The device has potential applications in other clinical conditions requiring occlusion of veins or arteries.« less

  14. Occlusal considerations in implant therapy: clinical guidelines with biomechanical rationale.

    PubMed

    Kim, Yongsik; Oh, Tae-Ju; Misch, Carl E; Wang, Hom-Lay

    2005-02-01

    Due to lack of the periodontal ligament, osseointegrated implants, unlike natural teeth, react biomechanically in a different fashion to occlusal force. It is therefore believed that dental implants may be more prone to occlusal overloading, which is often regarded as one of the potential causes for peri-implant bone loss and failure of the implant/implant prosthesis. Overloading factors that may negatively influence on implant longevity include large cantilevers, parafunctions, improper occlusal designs, and premature contacts. Hence, it is important to control implant occlusion within physiologic limit and thus provide optimal implant load to ensure a long-term implant success. The purposes of this paper are to discuss the importance of implant occlusion for implant longevity and to provide clinical guidelines of optimal implant occlusion and possible solutions managing complications related to implant occlusion. It must be emphasized that currently there is no evidence-based, implant-specific concept of occlusion. Future studies in this area are needed to clarify the relationship between occlusion and implant success.

  15. Dental occlusion, body posture and temporomandibular disorders: where we are now and where we are heading for.

    PubMed

    Manfredini, D; Castroflorio, T; Perinetti, G; Guarda-Nardini, L

    2012-06-01

    The aim of this investigation was to perform a review of the literature dealing with the issue of relationships between dental occlusion, body posture and temporomandibular disorders (TMD). A search of the available literature was performed to determine what the current evidence is regarding: (i) The physiology of the dental occlusion-body posture relationship, (ii) The relationship of these two topics with TMD and (iii) The validity of the available clinical and instrumental devices (surface electromyography, kinesiography and postural platforms) to measure the dental occlusion-body posture-TMD relationship. The available posturographic techniques and devices have not consistently found any association between body posture and dental occlusion. This outcome is most likely due to the many compensation mechanisms occurring within the neuromuscular system regulating body balance. Furthermore, the literature shows that TMD are not often related to specific occlusal conditions, and they also do not have any detectable relationships with head and body posture. The use of clinical and instrumental approaches for assessing body posture is not supported by the wide majority of the literature, mainly because of wide variations in the measurable variables of posture. In conclusion, there is no evidence for the existence of a predictable relationship between occlusal and postural features, and it is clear that the presence of TMD pain is not related with the existence of measurable occluso-postural abnormalities. Therefore, the use instruments and techniques aiming to measure purported occlusal, electromyographic, kinesiographic or posturographic abnormalities cannot be justified in the evidence-based TMD practice. © 2012 Blackwell Publishing Ltd.

  16. Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes

    PubMed Central

    Ouellette, Marie-Hélène

    2016-01-01

    The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo. Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells. In these contexts, protrusions adopt lamellipodia or an amoeboid morphology. We propose that lamella formation may reduce tension building at cell–cell junctions during morphogenesis. Cell-autonomous antagonism between these pathways enables cells to switch between Rac1- and RhoA-like morphogenetic programs. This study identifies the first case of cell-to-cell heterogeneity controlled by Rac1/RhoA antagonism during epidermal morphogenesis. PMID:27821782

  17. Nogo Receptor Homolog NgR2 Expressed in Sensory DRG Neurons Controls Epidermal Innervation by Interaction with Versican

    PubMed Central

    Bäumer, Bastian E.; Kurz, Antje; Borrie, Sarah C.; Sickinger, Stephan; Dours-Zimmermann, María T.; Zimmermann, Dieter R.

    2014-01-01

    Primary sensory afferents of the dorsal root ganglion (DRG) that innervate the skin detect a wide range of stimuli, such as touch, temperature, pain, and itch. Different functional classes of nociceptors project their axons to distinct target zones within the developing skin, but the molecular mechanisms that regulate target innervation are less clear. Here we report that the Nogo66 receptor homolog NgR2 is essential for proper cutaneous innervation. NgR2−/− mice display increased density of nonpeptidergic nociceptors in the footpad and exhibit enhanced sensitivity to mechanical force and innocuous cold temperatures. These sensory deficits are not associated with any abnormality in morphology or density of DRG neurons. However, deletion of NgR2 renders nociceptive nonpeptidergic sensory neurons insensitive to the outgrowth repulsive activity of skin-derived Versican. Biochemical evidence shows that NgR2 specifically interacts with the G3 domain of Versican. The data suggest that Versican/NgR2 signaling at the dermo-epidermal junction acts in vivo as a local suppressor of axonal plasticity to control proper density of epidermal sensory fiber innervation. Our findings not only reveal the existence of a novel and unsuspected mechanism regulating epidermal target innervation, but also provide the first evidence for a physiological role of NgR2 in the peripheral nervous system. PMID:24478347

  18. Nogo receptor homolog NgR2 expressed in sensory DRG neurons controls epidermal innervation by interaction with Versican.

    PubMed

    Bäumer, Bastian E; Kurz, Antje; Borrie, Sarah C; Sickinger, Stephan; Dours-Zimmermann, María T; Zimmermann, Dieter R; Bandtlow, Christine E

    2014-01-29

    Primary sensory afferents of the dorsal root ganglion (DRG) that innervate the skin detect a wide range of stimuli, such as touch, temperature, pain, and itch. Different functional classes of nociceptors project their axons to distinct target zones within the developing skin, but the molecular mechanisms that regulate target innervation are less clear. Here we report that the Nogo66 receptor homolog NgR2 is essential for proper cutaneous innervation. NgR2(-/-) mice display increased density of nonpeptidergic nociceptors in the footpad and exhibit enhanced sensitivity to mechanical force and innocuous cold temperatures. These sensory deficits are not associated with any abnormality in morphology or density of DRG neurons. However, deletion of NgR2 renders nociceptive nonpeptidergic sensory neurons insensitive to the outgrowth repulsive activity of skin-derived Versican. Biochemical evidence shows that NgR2 specifically interacts with the G3 domain of Versican. The data suggest that Versican/NgR2 signaling at the dermo-epidermal junction acts in vivo as a local suppressor of axonal plasticity to control proper density of epidermal sensory fiber innervation. Our findings not only reveal the existence of a novel and unsuspected mechanism regulating epidermal target innervation, but also provide the first evidence for a physiological role of NgR2 in the peripheral nervous system.

  19. Occlusion issues in early Renaissance art

    PubMed Central

    Gillam, Barbara

    2011-01-01

    Early Renaissance painters innovatively attempted to depict realistic three-dimensional scenes. A major problem was to produce the impression of overlap for surfaces that occlude one another in the scene but are adjoined in the picture plane. Much has been written about perspective in art but little about occlusion. Here I examine some of the strategies for depicting occlusion used by early Renaissance painters in relation to ecological considerations and perceptual research. Perceived surface overlap is often achieved by implementing the principle that an occluding surface occludes anything behind it, so that occlusion perception is enhanced by a lack of relationship of occluding contour to occluded contours. Some well-known figure-ground principles are also commonly used to stratify adjoined figures. Global factors that assist this stratification include the placement of figures on a ground plane, a high viewpoint, and figure grouping. Artists of this period seem to have differed on whether to occlude faces and heads, often carefully avoiding doing so. Halos were either eliminated selectively or placed oddly to avoid such occlusions. Finally, I argue that the marked intransitivity in occlusion by architecture in the paintings of Duccio can be related to the issue of perceptual versus cognitive influences on the visual impact of paintings. PMID:23145262

  20. Time to aortic occlusion: It's all about access.

    PubMed

    Romagnoli, Anna; Teeter, William; Pasley, Jason; Hu, Peter; Hoehn, Melanie; Stein, Deborah; Scalea, Thomas; Brenner, Megan

    2017-12-01

    Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less invasive method of proximal aortic occlusion compared with resuscitative thoracotomy with aortic cross-clamping (RTACC). This study compared time to aortic occlusion with REBOA and RTACC, both including and excluding time required for common femoral artery (CFA) cannulation. This was a retrospective, single-institution review of REBOA or RTACC performed between February 2013 and January 2016. Time of skin incision to aortic cross-clamp for RTACC, time required for CFA cannulation by percutaneous and open methods, and time from guide-wire insertion to balloon inflation at Zone 1 for REBOA, were obtained from videographic recordings. Eighteen RTACC and 21 REBOAs were performed. Median (Q1, Q3) time from skin incision to aortic cross-clamping was 317 seconds (227, 551 seconds). Median (Q1, Q3) time from start of arterial access to Zone 1 balloon occlusion was 474 seconds (431, 572 seconds) (vs. RTACC, p = 0.01). All REBOA procedures were performed with the same device. The median time to complete CFA cannulation was 247 seconds (range, 164-343 seconds), with no difference between percutaneous or open procedures (p = 0.07). The median (Q1, Q3) time to aortic occlusion in REBOA once arterial access had been established was 245 seconds (179, 295.5 seconds), which was significantly shorter than RTACC (p = 0.003). Once CFA access is achieved, time to aortic occlusion is faster with REBOA. Time to aortic occlusion is less than the time required to cannulate the CFA either by percutaneous or open approaches, emphasizing the importance of accurate and expedient CFA access. Resuscitative endovascular balloon occlusion of the aorta may represent a feasible alternative to thoracotomy for aortic occlusion. Time to aortic occlusion will likely decrease with the advent of newer REBOA technology. The rate-limiting portion of REBOA continues to be obtaining CFA access. Therapeutic, level V.

  1. Predictors of early stent occlusion among plastic biliary stents.

    PubMed

    Khashab, Mouen A; Kim, Katherine; Hutfless, Susan; Lennon, Anne Marie; Kalloo, Anthony N; Singh, Vikesh K

    2012-09-01

    A major disadvantage of plastic biliary stents is their short patency rates. The aim of this study was to identify predictors of early stent occlusion among patients receiving conventional plastic biliary stents. Early stent occlusion was defined as worsening cholestatic liver test results of a severity sufficiently significant to warrant ERCP with stent exchange prior to the planned stent exchange, or as symptoms of cholangitis. The association of cumulative stent diameter, demographics, stricture location, procedure indication, Charlson comorbidity index, history of prior early stent occlusion, presence of gallbladder, and performance of sphincteromy with the occurrence of early stent occlusion was studied using logistic regression and multivariate analysis. Our patient cohort comprised 343 patients (mean age 59.3 years) who underwent 561 ERCP procedures with the placement of one or more plastic biliary stents (mean number of stents per procedure 1.2, mean total diameter of stents per procedure 12 Fr). Early stent occlusion occurred in 73 (13 %) procedures. Female gender was protective against early stent occlusion (adjusted OR 0.54, 95 % CI 0.32-0.90, p = 0.02), while hilar stricture location was independently associated with a significantly increased risk of early stent occlusion (adjusted OR 3.41, 95 % CI 1.68-6.90, p = 0.0007). Early occlusion of conventional biliary stents occurred in 13 % of cases. While female gender decreased the risk of early stent occlusion, hilar stricture location was a significant predictor of early stent occlusion. Our results suggest that physicians should consider early elective stent exchange in patients with hilar strictures.

  2. Genetic analysis of Ras genes in epidermal development and tumorigenesis

    PubMed Central

    Drosten, Matthias; Lechuga, Carmen G; Barbacid, Mariano

    2013-01-01

    Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation. PMID:24150175

  3. Influence of denture adhesives on occlusion and disocclusion times.

    PubMed

    Abdelnabi, Mohamed Hussein; Swelem, Amal Ali; Al-Dharrab, Ayman A

    2016-03-01

    The effectiveness of adhesives in enhancing several functional aspects of complete denture performance has been well established. The direct influence of adhesives on occlusal contact simultaneity has not yet been investigated. The purpose of this crossover clinical trial was to evaluate quantitatively the influence of adhesives on occlusal balance by recording timed occlusal contacts; namely occlusion time (OT) and disocclusion time during right (DT-right) and left (DT-left) excursions by using computerized occlusal analysis. A crossover clinical trial was adopted. Assessments were carried out while participants (n=49) wore their dentures first without then with adhesives. Computerized occlusal analysis using the T-Scan III system was conducted to perform baseline computer-guided occlusal adjustment for conventionally fabricated dentures. Retention and stability assessment using the modified Kapur index and recording of OT and DT-right and DT-left values using the T-Scan III were subsequently carried out for all dentures, first without adhesives and then after application of adhesive. All T-Scan procedures were carried out by the same clinician. Wilcoxon signed-rank test was used to analyze the Kapur index scores and occlusal parameters (α=.05). Stability and retention of conventional dentures ranged initially from good to very good. However, adhesive application resulted in significant improvement (P<.001) in stability and retention and a significant decrease in duration of all occlusal parameters (OT [P=.003], DT-right [P=.003], and DT-left [P=.008]). Adhesives significantly decreased OT and DT durations in initially well-fitting complete dentures with fairly well balanced occlusion, and further enhanced denture stability and occlusal contact simultaneity. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  4. Load-bearing capacity of various CAD/CAM monolithic molar crowns under recommended occlusal thickness and reduced occlusal thickness conditions

    PubMed Central

    Choi, Sulki

    2017-01-01

    PURPOSE The goal of this study was to evaluate the fracture resistances of various monolithic crowns fabricated by computer-aided design and computer-aided manufacturing (CAD/CAM) with different thickness. MATERIALS AND METHODS Test dies were fabricated as mandibular molar forms with occlusal reductions using CAD/CAM. With different occlusal thickness (1.0 or 1.5 mm), a polymer-infiltrated ceramic network (Enamic, EN), and zirconia-reinforced lithium silicate (Suprinity, SU and Celtra-Duo, CD) were used to fabricate molar crowns. Lithium disilicate (e.max CAD, EM) crowns (occlusal: 1.5 mm) were fabricated as control. Seventy crowns (n=10 per group) were bonded to abutments and stored in water for 24 hours. A universal testing machine was used to apply load to crown until fracture. The fractured specimens were examined with a scanning electron microscopy. RESULTS The type of ceramics and the occlusal thickness showed a significant interaction. With a recommended thickness (1.5 mm), the SU revealed the mean load similar to the EM, higher compared with those of the EN and CD. The fracture loads in a reduced thickness (1.0 mm) were similar among the SU, CD, and EN. The mean fracture load of the SU and CD enhanced significantly when the occlusal thickness increased, whereas that of the EN did not. CONCLUSION The fracture loads of monolithic crowns were differently influenced by the changes in occlusal thickness, depending on the type of ceramics. Within the limitations of this study, all the tested crowns withstood the physiological masticatory loads both at the recommended and reduced occlusal thickness. PMID:29279761

  5. 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.

  6. Asymmetric distribution of Echinoid defines the epidermal leading edge during Drosophila dorsal closure

    PubMed Central

    Laplante, Caroline

    2011-01-01

    During Drosophila melanogaster dorsal closure, lateral sheets of embryonic epidermis assemble an actomyosin cable at their leading edge and migrate dorsally over the amnioserosa, converging at the dorsal midline. We show that disappearance of the homophilic cell adhesion molecule Echinoid (Ed) from the amnioserosa just before dorsal closure eliminates homophilic interactions with the adjacent dorsal-most epidermal (DME) cells, which comprise the leading edge. The resulting planar polarized distribution of Ed in the DME cells is essential for the localized accumulation of actin regulators and for actomyosin cable formation at the leading edge and for the polarized localization of the scaffolding protein Bazooka/PAR-3. DME cells with uniform Ed fail to assemble a cable and protrude dorsally, suggesting that the cable restricts dorsal migration. The planar polarized distribution of Ed in the DME cells thus provides a spatial cue that polarizes the DME cell actin cytoskeleton, defining the epidermal leading edge and establishing its contractile properties. PMID:21263031

  7. BAG-1 enhances cell-cell adhesion, reduces proliferation and induces chaperone-independent suppression of hepatocyte growth factor-induced epidermal keratinocyte migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hinitt, C.A.M.; Wood, J.; Lee, S.S.

    2010-08-01

    Cell motility is important in maintaining tissue homeostasis, facilitating epithelial wound repair and in tumour formation and progression. The aim of this study was to determine whether BAG-1 isoforms regulate epidermal cell migration in in vitro models of wound healing. In the human epidermal cell line HaCaT, endogenous BAG-1 is primarily nuclear and increases with confluence. Both transient and stable p36-Bag-1 overexpression resulted in increased cellular cohesion. Stable transfection of either of the three human BAG-1 isoforms p36-Bag-1 (BAG-1S), p46-Bag-1 (BAG-1M) and p50-Bag-1 (BAG-1L) inhibited growth and wound closure in serum-containing medium. However, in response to hepatocyte growth factor (HGF)more » in serum-free medium, BAG-1S/M reduced communal motility and colony scattering, but BAG-1L did not. In the presence of HGF, p36-Bag-1 transfectants retained proliferative response to HGF with no change in ERK1/2 activation. However, the cells retained E-cadherin localisation at cell-cell junctions and exhibited pronounced cortical actin. Point mutations in the BAG domain showed that BAG-1 inhibition of motility is independent of its function as a chaperone regulator. These findings are the first to suggest that BAG-1 plays a role in regulating cell-cell adhesion and suggest an important function in epidermal cohesion.« less

  8. Developmental patterning of sub-epidermal cells in the outer integument of Arabidopsis seeds

    PubMed Central

    Fiume, Elisa; Coen, Olivier; Xu, Wenjia; Lepiniec, Loïc

    2017-01-01

    The seed, the reproductive unit of angiosperms, is generally protected by the seed coat. The seed coat is made of one or two integuments, each comprising two epidermal cells layers and, in some cases, extra sub-epidermal cell layers. The thickness of the seed-coat affects several aspects of seed biology such as dormancy, germination and mortality. In Arabidopsis, the inner integument displays one or two sub-epidermal cell layers that originate from periclinal cell divisions of the innermost epidermal cell layer. By contrast, the outer integument was considered to be two-cell layered. Here, we show that sub-epidermal chalazal cells grow in between the epidermal outer integument cell layers to create an incomplete three-cell layered outer integument. We found that the MADS box transcription factor TRANSPARENT TESTA 16 represses growth of the chalaza and formation of sub-epidermal outer integument cells. Finally, we demonstrate that sub-epidermal cells of the outer and inner integument respond differently to the repressive mechanism mediated by FERTILIZATION INDEPENDENT SEED Polycomb group proteins and to fertilization signals. Our data suggest that integument cell origin rather than sub-epidermal cell position underlies different responses to fertilization. PMID:29141031

  9. Isolation of epidermal cells and cDNA cloning of TNF decoy receptor 3 of conger eel, Conger myriaster.

    PubMed

    Tsutsui, Shigeyuki; Yoshino, Yuko; Matsui, Saho; Nakamura, Osamu; Muramoto, Koji; Watanabe, Tasuku

    2008-03-01

    By using EDTA and a trypsin solution, we established a method for isolating the epidermal cells of the conger eel, Conger myriaster. We then identified TNF decoy receptor (DcR) cDNA in the species from a suppression subtractive hybridization library prepared from the epidermal cells stimulated with LPS. The full-length cDNA of conger TNF DcR (conDcR) consisted of 1479 base pairs, and the protein comprised 286 amino acid residues. Phylogenetic analysis indicated that conDcR was clustered into a DcR3 branch. ConDcR is likely to act as an important immune-regulating factor in inhibiting the apoptosis-inducing effect of TNF in the skin of conger eel.

  10. Hormonal regulation of growth and life span of bullfrog tadpole tail epidermal cells cultured in vitro.

    PubMed

    Nishikawa, A; Yoshizato, K

    1986-02-01

    Epidermal cells were dissociated from tails of the bullfrog tadpole, Rana catesbeiana, and cultured to investigate their response to steroid and thyroid hormones. Charcoal-treated serum (CTS) was used in the growth medium when cells were to be grown in the absence of steroid and thyroid hormones. The cells could be maintained for 2 weeks with a small increase in cell number in medium that contained CTS (CTS medium). Addition of cortisol to CTS medium increased both cellular attachment to the culture dishes and the proliferation of the attached cells with an optimum concentration of 5 X 10(-7) M. The cells remained viable and attached for at least a week. Cortisol stimulated the rate of protein synthesis 1.8-fold but did not alter the rate of DNA synthesis. The cells did not proliferate in the medium containing triiodothyronine (T3) and detached themselves from the dish within 5 days, which occurred in a dose-dependent manner with a maximum effect at 10(-8) M. It drastically decreased the rate of DNA synthesis but did not influence the rate of protein synthesis. These responses of cells to cortisol and T3 may reflect growth and death of tail epidermal cells in vivo at metamorphosis.

  11. Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters

    PubMed Central

    2017-01-01

    The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based pathway analysis were used to predict EGFR-mediated transporter regulation. Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS-MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1 and BCRP as well as their membrane expressions and transport activities, while MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were increased. AKT inhibition reduced all transporters. Exposure to methotrexate for 24 h led to a decreased viability, an effect that was reversed by cetuximab. In conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways. Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens possibilities for further research into nephroprotective comedication therapies. PMID:28493713

  12. Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters.

    PubMed

    Caetano-Pinto, Pedro; Jamalpoor, Amer; Ham, Janneke; Goumenou, Anastasia; Mommersteeg, Monique; Pijnenburg, Dirk; Ruijtenbeek, Rob; Sanchez-Romero, Natalia; van Zelst, Bertrand; Heil, Sandra G; Jansen, Jitske; Wilmer, Martijn J; van Herpen, Carla M L; Masereeuw, Rosalinde

    2017-06-05

    The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based pathway analysis were used to predict EGFR-mediated transporter regulation. Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS-MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1 and BCRP as well as their membrane expressions and transport activities, while MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were increased. AKT inhibition reduced all transporters. Exposure to methotrexate for 24 h led to a decreased viability, an effect that was reversed by cetuximab. In conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways. Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens possibilities for further research into nephroprotective comedication therapies.

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

    PubMed

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

    2016-02-01

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

  14. The temporal and spatial expression of Claudins in epidermal development and the accelerated program of epidermal differentiation in K14-CaSR transgenic mice.

    PubMed

    Troy, Tammy-Claire; Li, Yuhua; O'Malley, Lauren; Turksen, Kursad

    2007-02-01

    The importance of the epidermal permeability barrier (EPB) in protecting the mammalian species against harmful UV irradiation, microorganism invasion and water loss is well recognized, as is the role of calcium (Ca(2+)) in keratinocyte differentiation, cell-cell contact and the EPB. In a previous study, we reported that the overexpression of the Ca(2+)-sensing receptor (CaSR) in the undifferentiated basal cells of the epidermis induced a modified epidermal differentiation program including an accelerated EPB formation in transgenic mice, suggesting a role for CaSR signaling in the differentiation of embryonic epidermal cells during development. We now describe the expression profile of claudins (Cldns) and keratin markers in the accelerated EPB formation of K14-CaSR transgenic mice during development as compared to the wild type from E12.5 to newborn stages. Our data show that the transgenic epidermis undergoes an advanced epidermal differentiation program as compared to the wild type as evidenced morphologically as well as by the expression of K14, K1, loricrin, Cldn6, Cldn18 and Cldn11. In addition, we report for the first time the sequential expression of Cldns in epidermal development and describe that the localization of some Cldns change within the epidermis as it matures. Furthermore, we demonstrate that Cldn6 is expressed very early in epidermal morphogenesis, followed by Cldn18, Cldn11 and Cldn1.

  15. Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

    PubMed

    Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

    2005-01-01

    The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

  16. Signalling In The Epidermis: The E2f Cell Cycle Regulatory Pathway In Epidermal Morphogenesis, Regeneration And Transformation

    PubMed Central

    2005-01-01

    The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis. PMID:15951853

  17. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells

    PubMed Central

    Zhang, Hui-ming; Talbot, Mark J.; McCurdy, David W.; Patrick, John W.; Offler, Christina E.

    2015-01-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca2+ levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane–microtubule inter-relationship is discussed. PMID:26136268

  18. "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.

  19. Volumetric ambient occlusion for real-time rendering and games.

    PubMed

    Szirmay-Kalos, L; Umenhoffer, T; Toth, B; Szecsi, L; Sbert, M

    2010-01-01

    This new algorithm, based on GPUs, can compute ambient occlusion to inexpensively approximate global-illumination effects in real-time systems and games. The first step in deriving this algorithm is to examine how ambient occlusion relates to the physically founded rendering equation. The correspondence stems from a fuzzy membership function that defines what constitutes nearby occlusions. The next step is to develop a method to calculate ambient occlusion in real time without precomputation. The algorithm is based on a novel interpretation of ambient occlusion that measures the relative volume of the visible part of the surface's tangent sphere. The new formula's integrand has low variation and thus can be estimated accurately with a few samples.

  20. Varying face occlusion detection and iterative recovery for face recognition

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Hu, Zhengping; Sun, Zhe; Zhao, Shuhuan; Sun, Mei

    2017-05-01

    In most sparse representation methods for face recognition (FR), occlusion problems were usually solved via removing the occlusion part of both query samples and training samples to perform the recognition process. This practice ignores the global feature of facial image and may lead to unsatisfactory results due to the limitation of local features. Considering the aforementioned drawback, we propose a method called varying occlusion detection and iterative recovery for FR. The main contributions of our method are as follows: (1) to detect an accurate occlusion area of facial images, an image processing and intersection-based clustering combination method is used for occlusion FR; (2) according to an accurate occlusion map, the new integrated facial images are recovered iteratively and put into a recognition process; and (3) the effectiveness on recognition accuracy of our method is verified by comparing it with three typical occlusion map detection methods. Experiments show that the proposed method has a highly accurate detection and recovery performance and that it outperforms several similar state-of-the-art methods against partial contiguous occlusion.

  1. Dental cervical lesions associated with occlusal erosion and attrition.

    PubMed

    Khan, F; Young, W G; Shahabi, S; Daley, T J

    1999-09-01

    Acid demineralization of teeth causes occlusal erosion and attrition, and shallow and wedge-shaped cervical lesions putatively involving abfraction. From 250 patients with tooth wear, 122 with cervical lesions were identified. From epoxy resin replicas of their dentitions, associations of occlusal attrition or erosion or no wear with cervical lesions were recorded at 24 tooth sites (total 2928 sites). Criteria used to discriminate occlusal attrition from erosion, and shallow from grooved, wedge-shaped or restored cervical lesions were delineated by scanning electron microscopy. A 96 per cent association was found between occlusal and cervical pathology. Shallow cervical lesions were more commonly found in association with occlusal erosion. Wedge-shaped lesions were found equally commonly in association with occlusal erosion, as with attrition. Grooved and restored cervical lesions were uncommon. Differences were appreciated in the associations within incisor, canine, premolar and molar tooth sites which related more to the site-specificity of dental erosion than to attrition from occlusal forces. Non-carious lesions on teeth then have multifactorial aetiology and pathogenesis in which erosion and salivary protection play central roles. Dentists should primarily consider erosion in the diagnosis, prevention and treatment of tooth wear.

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

    PubMed

    Tokudome, Yoshihiro; Katayanagi, Mishina; Hashimoto, Fumie

    2015-06-01

    Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. 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. 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. 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. LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis.

  3. Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels.

    PubMed

    Schallreuter, Karin U; Salem, Mohamed A E L; Gibbons, Nick C J; Martinez, Aurora; Slominski, Radomir; Lüdemann, Jürgen; Rokos, Hartmut

    2012-06-01

    Vitiligo is characterized by a progressive loss of inherited skin color. The cause of the disease is still unknown. To date, there is accumulating in vivo and in vitro evidence for massive oxidative stress via hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONOO(-)) in the skin of affected individuals. Autoimmune etiology is the favored theory. Since depletion of the essential amino acid L-tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade, including serotonin and melatonin. Our in situ immunofluorescence and Western blot data reveal significantly lower TPH1 expression in patients with vitiligo. Expression is also low in melanocytes and keratinocytes under in vitro conditions. Although in vivo Fourier transform-Raman spectroscopy proves the presence of 5-hydroxytryptophan, epidermal TPH activity is completely absent. Regulation of TPH via microphthalmia-associated transcription factor and L-type calcium channels is severely affected. Moreover, dopa decarboxylase (DDC) expression is significantly lower, in association with decreased serotonin and melatonin levels. Computer simulation supports H(2)O(2)/ONOO(-)-mediated oxidation/nitration of TPH1 and DDC, affecting, in turn, enzyme functionality. Taken together, our data point to depletion of epidermal Trp by Fenton chemistry and exclude melatonin as a relevant contributor to epidermal redox balance and immune response in vitiligo.

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

    PubMed Central

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

    2016-01-01

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

  5. Part-time occlusion therapy for amblyopia in older children

    PubMed Central

    Singh, Inderpreet; Sachdev, Nishant; Kaushik, Sushmita

    2008-01-01

    Aim: To compare the efficacy of part-time versus full-time occlusion for treatment of amblyopia in children aged 7-12 years. Materials and Methods: Prospective interventional case series. One hundred children between 7-12 years of age with anisometropic (57), strabismic (25) and mixed (18) unilateral amblyopia were randomized (simple randomization) into four groups (25 each) to receive two hours, four hours, six hours or full-time occlusion therapy. Children were regularly followed up at six-weekly intervals for a minimum of three visits. Statistical Analysis: Intragroup visual improvement was analyzed using paired t-test while intergroup comparisons were done using ANOVA and unpaired t-test. Results: All four groups showed significant visual improvement after 18 weeks of occlusion therapy (P<0.001). Seventy-three (73%) of the total 100 eyes responded to amblyopia therapy with 11 eyes (44%), 17 eyes (68%), 22 eyes (88%) and 23 eyes (92%) being amblyopia responders in the four groups respectively, with the least number of responders in the two hours group. In mild to moderate amblyopia (vision 20/30 to 20/80), there was no significant difference in visual outcome among the four groups (P=0.083). However, in severe amblyopia (vision 20/100 or worse), six hours (P=0.048) and full-time occlusion (P=0.027) treatment were significantly more effective than two hours occlusion. Conclusion: All grades of part-time occlusion are comparable to full-time occlusion in effectiveness of treatment for mild to moderate amblyopia in children between 7-12 years of age unlike in severe amblyopia, where six hours and full-time occlusion were more effective than two hours occlusion therapy. PMID:18974515

  6. Part-time occlusion therapy for amblyopia in older children.

    PubMed

    Singh, Inderpreet; Sachdev, Nishant; Brar, Gagandeep S; Kaushik, Sushmita

    2008-01-01

    To compare the efficacy of part-time versus full-time occlusion for treatment of amblyopia in children aged 7-12 years. Prospective interventional case series. One hundred children between 7-12 years of age with anisometropic (57), strabismic (25) and mixed (18) unilateral amblyopia were randomized (simple randomization) into four groups (25 each) to receive two hours, four hours, six hours or full-time occlusion therapy. Children were regularly followed up at six-weekly intervals for a minimum of three visits. Intragroup visual improvement was analyzed using paired t-test while intergroup comparisons were done using ANOVA and unpaired t-test. All four groups showed significant visual improvement after 18 weeks of occlusion therapy ( P < 0.001). Seventy-three (73%) of the total 100 eyes responded to amblyopia therapy with 11 eyes (44%), 17 eyes (68%), 22 eyes (88%) and 23 eyes (92%) being amblyopia responders in the four groups respectively, with the least number of responders in the two hours group. In mild to moderate amblyopia (vision 20/30 to 20/80), there was no significant difference in visual outcome among the four groups ( P =0.083). However, in severe amblyopia (vision 20/100 or worse), six hours ( P =0.048) and full-time occlusion ( P =0.027) treatment were significantly more effective than two hours occlusion. All grades of part-time occlusion are comparable to full-time occlusion in effectiveness of treatment for mild to moderate amblyopia in children between 7-12 years of age unlike in severe amblyopia, where six hours and full-time occlusion were more effective than two hours occlusion therapy.

  7. Occlusal plane location in edentulous patients: a review.

    PubMed

    Shetty, Sanath; Zargar, Nazia Majeed; Shenoy, Kamalakanth; Rekha, V

    2013-09-01

    Occlusal plane orientation is an important factor in the construction of a complete denture. Occlusal plane could be oriented using landmarks in the mandibular arch as well as in the maxillary arch. In the mandibular arch there are few landmarks which could be used to orient the occlusal plane like the retromolar pad, corner of the lips (lower lip length) whereas the maxillary arch has a number of landmarks, of which the ala-tragal line is the most commonly used and the same being the most controversial. In the following article different landmarks and its accuracy for orientating the occlusal plane in an edentulous subject as studied by various authors has been discussed.

  8. Osteogenesis imperfecta with right renal artery occlusion

    PubMed Central

    Vaish, Arvind Kumar; Kumar, Nitin; Jain, Nirdesh; Agarwal, Abhishek

    2012-01-01

    We here report a case of osteogenesis imperfecta who presented with severe hypertension and left ventricular failure and had right renal artery occlusion. The case is very interesting as renal artery occlusion has not been reported earlier in osteogenesis imperfecta. PMID:22962392

  9. Proximal Occlusion of Medium-Sized Vessels with the Penumbra Occlusion Device: A Study of Safety and Efficacy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jambon, E.; Petitpierre, F.; Brizzi, V.

    PurposeTo retrospectively investigate the safety and efficacy of hybrid proximal coiling of various medium-sized vessels (4 to 8 mm) using the Penumbra Occlusion Device (POD).Materials and MethodsFrom October 2014 to February 2016, 37 proximal embolizations were performed with PODs in 36 patients (mean age: 50.8, range: 10–86; 29 male, 7 female). Vessel occlusions were achieved under fluoroscopic guidance using a 2.7 French microcatheter. Among the 36 vessels targeted, 16 were splenic arteries, 11 renal arteries, 4 mesenteric arteries, 3 arteriovenous fistulae, 1 iliac artery, and 1 gonadal vein. Intermittent follow-up angiography was performed to assess the flow for final occlusion. Outcomesmore » and complications were assessed by clinical and/or imaging follow-up.ResultsTo produce proximal occlusion of the intended vessels, the POD was used alone in 19 embolizations (51.4 %). In 12 procedures (32.4 %), POD was used as a coil constrainer to secure the coil construct. In 6 procedures (16.2 %), additional embolic devices were used to achieve vessel occlusion after initial POD deployment. After a mean follow-up of 3.2 months, no POD migration was observed but two complications occurred (5.4 %): one post embolic syndrome and one extensive infarction with splenic abscess.ConclusionThe POD system allows safe and effective proximal embolization of medium-sized vessels in a variety of clinical settings.« less

  10. 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

  11. A possible association of idiopathic osteosclerosis with excessive occlusal forces.

    PubMed

    Misirlioglu, Melda; Nalcaci, Rana; Baran, Ilgi; Adisen, Mehmet Zahit; Yilmaz, Selmi

    2014-03-01

    The aim of the study was to determine the relationship between idiopathic osteosclerotic lesions and occlusal forces using the T-Scan II computerized occlusal analysis device, and to test the sensitivity of the system in occlusal analysis. The study was conducted with 21 volunteers with idiopathic osteosclerosis (IO; 14 women, 7 men) aged between 17 and 62 years (mean 29.95). For every patient, seven or eight recordings were made with the T-Scan II occlusal analysis device in maximum intercuspation, and the last two (excluding any with technical problems) were chosen for evaluation. For each lesion-related area, the distribution of high occlusal forces from two different movies was analyzed. In 18 patients (85.71%), lesions were observed in an area of high occlusal force, and in 13 patients (61.9%), the lesions were located at the first area subjected to high occlusal forces. The percentage distribution of high forces at a lesion related area ranged from 0% to 88%. On average, the high forces at an osteosclerotic lesion area accounted for 20% of the maximum total force. No statistical differences were observed between the measurements of the two selected recordings (P > .05). The findings of this study suggest a possible relationship between IO and occlusal forces and primary contacts. T-Scan II was found to be a successful diagnostic device for detecting primary contacts and excessive occlusal forces.

  12. Efficacy of Epidermal Skin Grafts Over Complex, Chronic Wounds in Patients With Multiple Comorbidities.

    PubMed

    Fearmonti, Regina M

    2016-07-01

    Epidermal skin grafting presents an alternative to traditional autografts since only epidermal skin is harvested from the donor site. Split-thickness skin grafts are associated with difficulties at the donor site, including excessive pain, delayed healing, fluid loss, and unsatisfactory cosmetic results - all exacerbated in patients with comorbidities. A new automated epidermal harvesting tool (CelluTome Epidermal Harvesting System, KCI, an Acelity company, San Antonio, TX) involves concurrent application of heat and suction to normal skin to produce epidermal grafts. This article outlines the author's experience using this automated epidermal harvesting tool to harvest epidermal grafts and apply them on 23 chronic lower extremity wounds of patients with multiple comorbidities. Vacuum and heat were applied until epidermal microdomes were formed (30-45 minutes); an epidermal microdome array was collected onto a transfer dressing and applied over the wound. The automated harvesting tool yielded viable epithelium with every use. In addition to the epidermal skin graft, 16 of 23 wounds (70%) received adjunctive wound treatment, including negative pressure wound therapy, hyperbaric oxygen therapy, and/or regenerative tissue matrix. The average reepithelialization rate was 88.1% during a mean follow-up period of 76.4 days; no use of an anesthetic/operating room was required for the procedure. All donor sites were completely healed within 2 weeks without complications or scarring. Epidermal skin grafting provided a simplified, office-based grafting option with no donor site morbidity, and assisted in closure or size reduction of chronic wounds in this series.

  13. The organization of human epidermis: functional epidermal units and phi proportionality.

    PubMed

    Hoath, Steven B; Leahy, D G

    2003-12-01

    The concept that mammalian epidermis is structurally organized into functional epidermal units has been proposed on the basis of stratum corneum (SC) architecture, proliferation kinetics, melanocyte:keratinocyte ratios (1:36), and, more recently, Langerhans cell: epidermal cell ratios (1:53). This article examines the concept of functional epidermal units in human skin in which the maintenance of phi (1.618034) proportionality provides a central organizing principle. The following empirical measurements were used: 75,346 nucleated epidermal cells per mm2, 1394 Langerhans cells per mm2, 1999 melanocytes per mm2, 16 (SC) layers, 900-microm2 corneocyte surface area, 17,778 corneocytes per mm2, 14-d (SC) turnover time, and 93,124 per mm2 total epidermal cells. Given these empirical data: (1) the number of corneocytes is a mean proportional between the sum of the Langerhans cell + melanocyte populations and the number of epidermal cells, 3393/17,778-17,778/93,124; (2) the ratio of nucleated epidermal cells over corneocytes is phi proportional, 75,346/17,778 approximately phi3; (3) assuming similar 14-d turnover times for the (SC) and Malpighian epidermis, the number of corneocytes results from subtraction of a cellular fraction equal to approximately 2/phi2 x the number of living cells, 75,436 - (2/phi2 x 75,346) approximately 17,778; and (4) if total epidermal turnover time equals (SC) turnover time x the ratio of living/dead cells, then compartmental turnover times are unequal (14 d for (SC) to 45.3 d for nucleated epidermis approximately 1/2phi) and cellular replacement rates are 52.9 corneocytes/69.3 keratinocytes per mm2 per h approximately 2/phi2. These empirically derived equivalences provide logicomathematical support for the presence of functional epidermal units in human skin. Validation of a phi proportional unit architecture in human epidermis will be important for tissue engineering of skin and the design of instruments for skin measurement.

  14. The group of epidermal nevus syndromes Part I. Well defined phenotypes.

    PubMed

    Happle, Rudolf

    2010-07-01

    The epidermal nevus syndromes represent a group of distinct disorders that can be distinguished by the type of associated epidermal nevus and by the criterion of presence or absence of heritability. Well defined syndromes characterized by organoid epidermal nevi include Schimmelpenning syndrome, phacomatosis pigmentokeratotica, nevus comedonicus syndrome, angora hair nevus syndrome, and Becker nevus syndrome. The molecular basis of these disorders has so far not been identified. By contrast, the group of syndromes characterized by keratinocytic nevi comprises three phenotypes with a known molecular etiology in the form of CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, type 2 segmental Cowden disease, and fibroblast growth factor receptor 3 epidermal nevus syndrome (García-Hafner-Happle syndrome), whereas Proteus syndrome is still of unknown origin. From this overview, it is clear that a specific type of these disorders cannot be classified by the name "epidermal nevus syndrome" nor by the terms "organoid nevus syndrome" or "keratinocytic nevus syndrome." After completing this learning activity, participants should be able to distinguish nine different epidermal nevus syndromes by their characteristic features, understand the practical significance of avoiding terms like "epidermal nevus syndrome" or "keratinocytic nevus syndrome" to define any specific entity within this group of disorders, and differentiate between nonhereditary traits and those bearing a genetic risk because of either Mendelian or non-Mendelian inheritance. Copyright (c) 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  15. A protocol for characterizing the impact of collateral flow after distal middle cerebral artery occlusion

    PubMed Central

    DeFazio, R. Anthony; Levy, Sean; Morales, Carmen L.; Levy, Rebecca V.; Dave, Kunjan R.; Lin, Hung W.; Abaffy, Tatjana; Watson, Brant D.; Perez-Pinzon, Miguel A.; Ohanna, Victoria

    2010-01-01

    I. SUMMARY In humans and in animal models of stroke, collateral blood flow between territories of the major pial arteries has a profound impact on cortical infarct size. However, there is a gap in our understanding of the genetic determinants of collateral formation and flow, as well as the signaling pathways and neurovascular interactions regulating this flow. Previous studies have demonstrated that collateral flow between branches of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) can protect mouse cortex from infarction after middle cerebral artery occlusion. Because the number and diameter of collaterals varies among mouse strains and after transgenic manipulations, a combination of methods is required to control for these variations. Here, we report an inexpensive approach to characterizing the cerebrovascular anatomy, and in vivo monitoring of cerebral blood flow as well. Further, we introduce a new, minimally invasive method for the occlusion of distal MCA branches. These methods will permit a new generation of studies on the mechanisms regulating collateral remodeling and cortical blood flow after stroke. PMID:21593993

  16. Inhibition of epidermal growth factor receptor by ferulic acid and 4-vinylguaiacol in human breast cancer cells.

    PubMed

    Sudhagar, S; Sathya, S; Anuradha, R; Gokulapriya, G; Geetharani, Y; Lakshmi, B S

    2018-02-01

    To examine the potential of ferulic acid and 4-vinylguaiacol for inhibiting epidermal growth factor receptor (EGFR) in human breast cancer cells in vitro. Ferulic acid and 4-vinylguaiacol limit the EGF (epidermal growth factor)-induced breast cancer proliferation and new DNA synthesis. Western blot analysis revealed both ferulic acid and 4-vinylguaiacol exhibit sustained inhibition of EGFR activation through down-regulation of Tyr 1068 autophosphorylation. Molecular docking analysis shows ferulic acid forming hydrogen bond interaction with Lys 745 and Met 793 whereas, 4-vinylguaiacol forms two hydrogen bonds with Phe 856 and exhibits stronger hydrophobic interactions with multiple amino acid residues at the EGFR kinase domain. Ferulic acid and 4-vinylguaiacol could serve as a potential structure for the development of new small molecule therapeutics against EGFR.

  17. Occlusal contact of fixed implant prostheses using functional bite impression technique.

    PubMed

    Suzuki, Yasunori; Shimpo, Hidemasa; Ohkubo, Chikahiro

    2015-02-01

    Functional bite impression (FBI) has been described as a definitive impression made under occlusal force after functional generated path (FGP) recording. This study compared the accuracy of occlusal contact of implant-fixed prostheses using the FBI technique and the conventional impression technique. Twelve subjects, each missing a single premolar or molar, were selected for this study. The conditions of the occlusal contacts were identified by the modified transillumination method. The occlusal contact condition was determined by comparing the rate of change in the occlusal contact area of the implant-fixed prostheses and both adjacent teeth before and after occlusal adjustment. The rate of change in the occlusal contact area using the FBI technique was 96%, and the rate using the conventional technique was 54%. The occlusal contact of implant prostheses using the FBI technique revealed better accuracy than that of the conventional technique. Regarding the FBI technique, a precise and functional prosthesis could be produced by completing the maxillomandibular registration, impression, and FGP at the same time.

  18. 21 CFR 870.2890 - Vessel occlusion transducer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Vessel occlusion transducer. 870.2890 Section 870.2890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2890 Vessel occlusion...

  19. 21 CFR 870.2890 - Vessel occlusion transducer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vessel occlusion transducer. 870.2890 Section 870.2890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2890 Vessel occlusion...

  20. Does compliance with amblyopia management improve following supervised occlusion treatment?

    PubMed

    El-Ghrably, I A; Longville, D; Gnanaraj, L

    2007-01-01

    To demonstrate improvement in compliance following supervised occlusion therapy for amblyopia in children who had failed to respond to outpatient treatment. Retrospective review of the visual outcome of 30 children who were admitted to an ophthalmology ward for 1-day intensive supervised occlusion. These children had documented poor compliance and previously failed to respond to the outpatient occlusion treatment. During their stay a trained ophthalmology nurse educated parents regarding amblyopia and the benefits of occlusion therapy. Visual acuity (VA) of the amblyopic and fellow eyes was recorded on admission, discharge, and at each subsequent visit. The compliance was recorded from parent's history and also indirectly by noticing improvement in vision. The mean supervised occlusion was 7.4 hours (range 4-12 hours). The compliance with occlusion therapy improved in 23 children (77%) after discharge. The mean duration of occlusion after discharge improved to 4 hours (range 1-12 hours). The mean follow-up was 18 months (range 4-24 months). Though there was no dramatic improvement in VA at discharge there was a statistically significant improvement in VA between admission and last recorded VA (p<0.0001). Of the 23 children who were compliant with occlusion following discharge, 21 (91%) gained at least one line of acuity in their amblyopic eye on the last assessment of their VA and five of them achieved 6/12. Of the seven children who did not comply with occlusion following discharge, only one patient gained one line improvement in his amblyopic eye. This study shows that supervised occlusion treatment and parental education was effective in children who had initially failed traditional outpatient treatment.

  1. [Cilioretinal artery occlusion and central retinal vein occlusion complicating hyperhomocysteinemia: a case report].

    PubMed

    Berkani, Z; Kitouni, Y; Belhadj, A; Sifi, K; Abbadi, N; Bellatrache, C; Hartani, D; Kherroubi, R

    2013-09-01

    Hyperhomocysteinemia is known to be a risk factor in both retinal artery and retinal vein occlusions. We report the case of a young patient with combined occlusion of the cilioretinal artery and the central retinal vein due to hyperhomocysteinemia. A 23-year-old patient without significant medical history, presented for sudden, painless visual loss in the right eye. Ophthalmologic examination revealed best-corrected visual acuity of the right eye 8/10 P2, and 10/10 P2 on the left. Anterior segment exam was normal in both eyes, while the right fundus revealed white, ischemic edema, centered around a cilioretinal artery, sparing the fovea, with some hemorrhagic spots and disc edema. Fluorescein angiography confirmed delayed filling of the right cilioretinal artery and revealed a normal disc on the left. Two weeks later, the clinical picture had evolved into a right ischemic CRVO, confirmed by a second angiogram, with a decrease in visual acuity to 3/10. A work-up was performed, including: a full lipid profile, serum electrolytes, ESR, CRP, a complete blood count (leukocytes, platelets, hemoglobin were normal), a coagulation work-up (PT, PTT, protein C, protein S, antithrombin III, factor V Leiden were normal), ANCA, antiphospholipid antibodies and antinuclear antibodies were negative, and finally cardiology studies (cardiac echo, carotid Doppler) and neurology (brain MRI) were ordered and came back normal. Otherwise, plasma homocysteine was moderately high on two samples, at 18.3 μmol/L and 17.78 μmol/L. Thyroid and renal work-ups were ordered. Urgent PRP was performed, and vitamin therapy (vitB12, vitB6, folic acid) was instituted. The subsequent course was remarkable for recovery of visual acuity to 10/10, P2 with persistence of an inferior altitudinal central scotoma. MTHFR C677T polymorphism was negative. Retinal vascular occlusions (RVO) are serious events, which require investigation for underlying systemic disease, which can be life-threatening. The clinical

  2. 21 CFR 878.4020 - Occlusive wound dressing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Occlusive wound dressing. 878.4020 Section 878.4020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4020 Occlusive wound dressing...

  3. 21 CFR 878.4020 - Occlusive wound dressing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Occlusive wound dressing. 878.4020 Section 878.4020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4020 Occlusive wound dressing...

  4. 21 CFR 878.4020 - Occlusive wound dressing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Occlusive wound dressing. 878.4020 Section 878.4020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4020 Occlusive wound dressing...

  5. In vitro reproduction of incisal/occlusal cupping/cratering.

    PubMed

    Dzakovich, John J; Oslak, Robert R

    2013-06-01

    Occlusal cupping/cratering (depressed dentin surrounded by elevated rims of enamel) has been postulated to be the result of abrasion, bruxism, attrition, acid erosion, stress corrosion, or a combination of these. The primary etiology or the multifactorial sequence of occlusal cupping/cratering remains scientifically unsubstantiated. The purpose of this study was to reproduce occlusal/incisal cupping/cratering in vitro. This study was designed to create cupping/cratering on the occlusal surfaces of extracted human teeth rather than to quantify the amount of lost tooth structure caused by abrasion. One name-brand toothbrush was tested with 2 different dentifrices (of different abrasive potentials [low and high]) and water only (nonabrasive) on extracted human teeth. Six specimens of 4 teeth each (24 teeth) were subjected to horizontal brushing in a 1:1 toothpaste/water slurry and water only. The control group, brushed with water only, demonstrated no visible loss of tooth structure. Each of the specimens brushed with toothpaste, regardless of the degree of abrasivity, demonstrated visible wear of the dentin, resulting in occlusal/incisal cupping/cratering. Pronounced cupping/cratering was caused by horizontal brushing with commercial toothpastes. Brushing in water demonstrated no visual loss of occlusal tooth structure. (J Prosthet Dent 2013;109:384-391). Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  6. The tyrosine kinase Stitcher activates Grainy head and epidermal wound healing in Drosophila.

    PubMed

    Wang, Shenqiu; Tsarouhas, Vasilios; Xylourgidis, Nikos; Sabri, Nafiseh; Tiklová, Katarína; Nautiyal, Naumi; Gallio, Marco; Samakovlis, Christos

    2009-07-01

    Epidermal injury initiates a cascade of inflammation, epithelial remodelling and integument repair at wound sites. The regeneration of the extracellular barrier and damaged tissue repair rely on the precise orchestration of epithelial responses triggered by the injury. Grainy head (Grh) transcription factors induce gene expression to crosslink the extracellular barrier in wounded flies and mice. However, the activation mechanisms and functions of Grh factors in re-epithelialization remain unknown. Here we identify stitcher (stit), a new Grh target in Drosophila melanogaster. stit encodes a Ret-family receptor tyrosine kinase required for efficient epidermal wound healing. Live imaging analysis reveals that Stit promotes actin cable assembly during wound re-epithelialization. Stit activation also induces extracellular signal-regulated kinase (ERK) phosphorylation along with the Grh-dependent expression of stit and barrier repair genes at the wound sites. The transcriptional stimulation of stit on injury triggers a positive feedback loop increasing the magnitude of epithelial responses. Thus, Stit activation upon wounding coordinates cytoskeletal rearrangements and the level of Grh-mediated transcriptional wound responses.

  7. Endovascular Treatment of Veno-Occlusive Behcet's Disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tekbas, Guven, E-mail: drgtekbas@gmail.com; Oguzkurt, Levent, E-mail: loguzkurt@yahoo.com; Gur, Serkan, E-mail: mserkangur@yahoo.com

    Purpose: To retrospectively evaluate the outcome of endovascular treatments for patients with chronic veno-occlusive disease in different vascular beds secondary to Behcet's disease (BD). There are few case reports on the subject, and this is the largest study to date. Materials and Methods: From January 2001 through October 2009, chronic venous occlusions were treated in 10 patients (all male [age range 18-76 years]) with BD using percutaneous transluminal angioplasty and/or stent placement. All patients were symptomatic and had chronic iliofemoral deep venous thrombosis (DVT; n = 5), central venous occlusion (n = 3), or Budd-Chiari syndrome (BCS; n = 2).more » All patients met criteria of the International Study Group on Behcet's Disease. Results: Two of five patients with DVT had unsuccessful recanalization attempts. Three patients had successful recanalization with stent placement. All three veins were occluded within 1 month with unsuccessful reinterventions. Three patients with chronic central venous occlusion had successful recanalization with percutaneous transluminal angioplasty (n = 1) and stent placement (n = 2). Two patients had reocclusion with successful reintervention. Two BCS patients had successful treatment with stent placements. Overall technical success was 69%, and no procedural complications were encountered. None of the patients with chronic DVT had patent veins; however, all patients with central venous occlusion or BCS had patent veins on color Doppler ultrasonography at follow-up ranging from 3 to 48 months after intervention. Conclusion: Endovenous treatment for chronic iliofemoral DVT due to BD had a poor outcome. However, long-term outcome after endovenous treatment for upper-extremity central venous occlusion and BCS syndrome was good.« less

  8. Compliance with occlusion therapy for childhood amblyopia.

    PubMed

    Wallace, Michael P; Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

    2013-09-17

    Explore compliance with occlusion treatment of amblyopia in the Monitored and Randomized Occlusion Treatment of Amblyopia Studies (MOTAS and ROTAS), using objective monitoring. Both studies had a three-phase protocol: initial assessment, refractive adaptation, and occlusion. In the occlusion phase, participants were instructed to dose for 6 hours/day (MOTAS) or randomized to 6 or 12 hour/day (ROTAS). Dose was monitored continuously using an occlusion dose monitor (ODM). One hundred and fifty-two patients (71 male, 81 female; 122 Caucasian, 30 non-Caucasian) of mean ± SD age 68 ± 18 months participated. Amblyopia was defined as an interocular acuity difference of at least 0.1 logMAR and was associated with anisometropia in 50, strabismus in 44, and both (mixed) in 58. Median duration of occlusion was 99 days (interquartile range 72 days). Mean compliance was 44%, mean proportion of days with no patch worn was 42%. Compliance was lower (39%) on weekends compared with weekdays (46%, P = 0.04), as was the likelihood of dosing at all (52% vs. 60%, P = 0.028). Compliance was lower when attendance was less frequent (P < 0.001) and with prolonged treatment duration (P < 0.001). Age, sex, amblyopia type, and severity were not associated with compliance. Mixture modeling suggested three subpopulations of patch day doses: less than 30 minutes; doses that achieve 30% to 80% compliance; and doses that achieve around 100% compliance. This study shows that compliance with patching treatment averages less than 50% and is influenced by several factors. A greater understanding of these influences should improve treatment outcome. (ClinicalTrials.gov number, NCT00274664).

  9. Relationship between Endopolyploidy and Cell Size in Epidermal Tissue of Arabidopsis.

    PubMed Central

    Melaragno, JE; Mehrotra, B; Coleman, AW

    1993-01-01

    Relative quantities of DNA in individual nuclei of stem and leaf epidermal cells of Arabidopsis were measured microspectrofluorometrically using epidermal peels. The relative ploidy level in each nucleus was assessed by comparison to root tip mitotic nuclei. A clear pattern of regular endopolyploidy is evident in epidermal cells. Guard cell nuclei contain levels of DNA comparable to dividing root cells, the 2C level (i.e., one unreplicated copy of the nuclear DNA). Leaf trichome nuclei had elevated ploidy levels of 4C, 8C, 16C, 32C, and 64C, and their cytology suggested that the polyploidy represents a form of polyteny. The nuclei of epidermal pavement cells were 2C, 4C, and 8C in stem epidermis, and 2C, 4C, 8C, and 16C in leaf epidermis. Morphometry of epidermal pavement cells revealed a direct proportionality between nuclear DNA level and cell size. A consideration of the development process suggests that the cells of highest ploidy level are developmentally oldest; consequently, the developmental pattern of epidermal tissues can be read from the ploidy pattern of the cells. This observation is relevant to theories of stomate spacing and offers opportunities for genetic analysis of the endopolyploidy/polyteny phenomenon. PMID:12271050

  10. CAPRICE positively regulates stomatal formation in the Arabidopsis hypocotyl

    PubMed Central

    2008-01-01

    In the Arabidopsis hypocotyl, stomata develop only from a set of epidermal cell files. Previous studies have identified several negative regulators of stomata formation. Such regulators also trigger non-hair cell fate in the root. Here, it is shown that TOO MANY MOUTHS (TMM) positively regulates CAPRICE (CPC) expression in differentiating stomaless-forming cell files, and that the CPC protein might move to the nucleus of neighbouring stoma-forming cells, where it promotes stomata formation in a redundant manner with TRIPTYCHON (TRY). Unexpectedly, the CPC protein was also localized in the nucleus and peripheral cytoplasm of hypocotyl fully differentiated epidermal cells, suggesting that CPC plays an additional role to those related to stomata formation. These results identify CPC and TRY as positive regulators of stomata formation in the embryonic stem, which increases the similarity between the genetic control of root hair and stoma cell fate determination. PMID:19513241

  11. GRHL3/GET1 and Trithorax Group Members Collaborate to Activate the Epidermal Progenitor Differentiation Program

    PubMed Central

    Hopkin, Amelia Soto; Gordon, William; Klein, Rachel Herndon; Espitia, Francisco; Daily, Kenneth; Zeller, Michael; Baldi, Pierre; Andersen, Bogi

    2012-01-01

    The antagonistic actions of Polycomb and Trithorax are responsible for proper cell fate determination in mammalian tissues. In the epidermis, a self-renewing epithelium, previous work has shown that release from Polycomb repression only partially explains differentiation gene activation. We now show that Trithorax is also a key regulator of epidermal differentiation, not only through activation of genes repressed by Polycomb in progenitor cells, but also through activation of genes independent of regulation by Polycomb. The differentiation associated transcription factor GRHL3/GET1 recruits the ubiquitously expressed Trithorax complex to a subset of differentiation genes. PMID:22829784

  12. Combining technologies: a computerized occlusal analysis system synchronized with a computerized electromyography system.

    PubMed

    Kerstein, Robert B

    2004-04-01

    Current advances in computer technologies have afforded dentists precision ways to examine occlusal contacts and muscle function. Recently, two separate computer technologies have been synchronized together, so that an operator can record their separate diagnostic data simultaneously. The two systems are: the T Scan II Occlusal Analysis System and the Biopak Electromyography Recording System. The simultaneous recording and playback capacity of these two computer systems allows the operator to analyze and correlate specific occlusal moments to specific electromyographic changes that result from these occlusal moments. This synchronization provides unparalleled evidence of the effect occlusal contact arrangement has on muscle function. Therefore, the occlusal condition of an inserted dental prosthesis or the occlusal scheme of the natural teeth (before and after corrective occlusal adjustments) can be readily evaluated, documented, and quantified for both, quality of occlusal parameters and muscle activity and the responses to the quality of the occlusal condition. This article describes their synchronization and illustrates their use in performing precision occlusal adjustment procedures on two patients: one who demonstrates occlusal disharmony while exhibiting the signs and symptoms of chronic myofascial pain dysfunction syndrome, and the other who had extensive restorative work accomplished but exhibits occlusal discomfort post-operatively.

  13. Melorheostosis with occlusion of dorsalis pedis artery.

    PubMed

    Ishibe, Motomi; Inoue, Masayuki; Saitou, Katsutoshi

    2002-02-01

    Melorheostosis is an unusual sclerotic dysplasia of bone. The case of a 51-year-old female patient with melorheostosis and occlusion of the dorsalis pedis artery is described. Although numerous vascular anomalies have been noted in patients with melorheostosis, occlusion of the dorsalis pedis artery has not been reported previously.

  14. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells.

    PubMed

    Zhang, Hui-ming; Talbot, Mark J; McCurdy, David W; Patrick, John W; Offler, Christina E

    2015-09-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. Amalric sign: An augur of ophthalmic artery occlusion

    PubMed Central

    Hande, Prathibha; Sinha, Babi; Nayak, Shivani; Srinivasan, Srilakshmi; Shetty, Jyothi

    2017-01-01

    A 75-year-old man presented to us with sudden onset of profound vision loss in his right eye and was identified as suffering from an ophthalmic artery occlusion. Apart from the retinal whitening and box-carring of the retinal arteries, there were characteristic triangular patches of retinal whitening in the midperipheral temporal fundus indicating a previous lateral posterior choroidal artery occlusion. The patient was a chronic smoker and had dyslipidemia. The carotid Doppler study showed complete occlusion of the internal carotid artery. The presence of these triangular patches of retinal whitening or amalric sign can therefore herald a more proximal vessel occlusion. Hence such patients require evaluation on an emergency basis. The characteristic features of the patches on fluorescein angiography and indocyanine green angiography are discussed here. PMID:29044080

  16. Amalric sign: An augur of ophthalmic artery occlusion.

    PubMed

    Hande, Prathibha; Sinha, Babi; Nayak, Shivani; Srinivasan, Srilakshmi; Shetty, Jyothi

    2017-10-01

    A 75-year-old man presented to us with sudden onset of profound vision loss in his right eye and was identified as suffering from an ophthalmic artery occlusion. Apart from the retinal whitening and box-carring of the retinal arteries, there were characteristic triangular patches of retinal whitening in the midperipheral temporal fundus indicating a previous lateral posterior choroidal artery occlusion. The patient was a chronic smoker and had dyslipidemia. The carotid Doppler study showed complete occlusion of the internal carotid artery. The presence of these triangular patches of retinal whitening or amalric sign can therefore herald a more proximal vessel occlusion. Hence such patients require evaluation on an emergency basis. The characteristic features of the patches on fluorescein angiography and indocyanine green angiography are discussed here.

  17. Intravitreal triamcinolone acetonide injections in the treatment of retinal vein occlusions.

    PubMed

    Roth, Daniel B; Cukras, Catherine; Radhakrishnan, Ravi; Feuer, William J; Yarian, David L; Green, Stuart N; Wheatley, Harold M; Prenner, Jonathan

    2008-01-01

    To report the visual acuity response after intravitreal triamcinolone injection in patients with macular edema due to retinal vein occlusions. Retrospective nonrandomized interventional series of 172 consecutive patients with macular edema due to retinal vein occlusions who were treated with intravitreal triamcinolone acetonide injection. Patients underwent Snellen visual acuity testing and ophthalmoscopic examination at baseline and 1, 3, 6, and 12 months after intravitreal triamcinolone acetonide injection. All subtypes of retinal vein occlusions showed significant improvements in mean visual acuity 1 month after injection. This improvement in visual acuity was maintained over the 12-month period for all but the central retinal vein occlusion group. Seventy-one (41.3%) of the 172 patients received more than one intravitreal triamcinolone injection for unresolved or recurrent macular edema. This study demonstrates a benefit associated with intravitreal triamcinolone acetonide injection for retinal vein occlusions that was maintained by patients with branch retinal vein occlusions and hemiretinal vein occlusions over a 12-month period. Visual acuity improvement was not maintained in patients with central retinal vein occlusions with this course of treatment.

  18. Progression of Diabetic Capillary Occlusion: A Model

    PubMed Central

    Gens, John Scott; Glazier, James A.; Burns, Stephen A.; Gast, Thomas J.

    2016-01-01

    An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions. PMID:27300722

  19. Biochemistry of epidermal stem cells.

    PubMed

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

    2013-02-01

    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. 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. 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. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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

  1. Retinal vein occlusion

    MedlinePlus

    ... of one eye. Exams and Tests Tests to evaluate for vein occlusion include: Exam of the retina after dilating the pupil An eye test that uses a special dye and camera to look at blood flow in the retina and choroid. Intraocular pressure Pupil ...

  2. 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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  3. Role of occlusion in endodontic management: report of two cases.

    PubMed

    Yu, Christine Y

    2004-12-01

    The two clinical cases reported demonstrate that traumatic occlusion can play a role in the initiation and progression of pulp and periradicular inflammation. The symptom of persistent pain did not subside after the commencement of endodontic treatment. Traumatic occlusion was identified in both cases to be the main cause and hence occlusal adjustment was performed. This resulted in the gradual resolution of the symptoms. The findings suggest that occlusal trauma is often overlooked in the diagnosis and management of endodontic diseases.

  4. Haptic simulation framework for determining virtual dental occlusion.

    PubMed

    Wu, Wen; Chen, Hui; Cen, Yuhai; Hong, Yang; Khambay, Balvinder; Heng, Pheng Ann

    2017-04-01

    The surgical treatment of many dentofacial deformities is often complex due to its three-dimensional nature. To determine the dental occlusion in the most stable position is essential for the success of the treatment. Computer-aided virtual planning on individualized patient-specific 3D model can help formulate the surgical plan and predict the surgical change. However, in current computer-aided planning systems, it is not possible to determine the dental occlusion of the digital models in the intuitive way during virtual surgical planning because of absence of haptic feedback. In this paper, a physically based haptic simulation framework is proposed, which can provide surgeons with the intuitive haptic feedback to determine the dental occlusion of the digital models in their most stable position. To provide the physically realistic force feedback when the dental models contact each other during the searching process, the contact model is proposed to describe the dynamic and collision properties of the dental models during the alignment. The simulated impulse/contact-based forces are integrated into the unified simulation framework. A validation study has been conducted on fifteen sets of virtual dental models chosen at random and covering a wide range of the dental relationships found clinically. The dental occlusions obtained by an expert were employed as a benchmark to compare the virtual occlusion results. The mean translational and angular deviations of the virtual occlusion results from the benchmark were small. The experimental results show the validity of our method. The simulated forces can provide valuable insights to determine the virtual dental occlusion. The findings of this work and the validation of proposed concept lead the way for full virtual surgical planning on patient-specific virtual models allowing fully customized treatment plans for the surgical correction of dentofacial deformities.

  5. Genomic determinants of epidermal appendage patterning and structure in domestic birds

    PubMed Central

    Boer, Elena F.; Van Hollebeke, Hannah F.; Shapiro, Michael D.

    2017-01-01

    Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity. PMID:28347644

  6. Genomic determinants of epidermal appendage patterning and structure in domestic birds.

    PubMed

    Boer, Elena F; Van Hollebeke, Hannah F; Shapiro, Michael D

    2017-09-15

    Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Evaluation of the occlusal contact of crowns fabricated with the bite impression method.

    PubMed

    Makino, Sachi; Okada, Daizo; Shin, Chiharu; Ogura, Reiko; Ikeda, Masaomi; Miura, Hiroyuki

    2013-09-30

    In prosthodontic treatment, reconstruction of a proper occlusal contact relationship is very important as well as reconstruction of a proper interproximal relationship and marginal fitness. Unfortunately, occlusal relationships are sometimes lost in the process of occlusal adjustment of crowns. The purpose of this study was to compare the occlusal contacts of single crown fabricated by two different types of impression techniques. Nine subjects, whose molars required treatment with crown restoration, were enrolled in this study. Full cast crowns were fabricated using two types of impression techniques: the conventional impression method (CIM) and the bite impression method (BIM). The occlusal contacts of crowns were precisely evaluated at the following stages: after occlusal adjustment on the articulator (Step 0), before occlusal adjustment in the mouth (Step 1), after occlusal adjustment at the intercuspal position (Step 2), and after occlusal adjustment during lateral and protrusive excursions (Step 3). The number of occlusal contacts of the crowns on the functional cusps fabricated with BIM was significantly greater than that with CIM after occlusal adjustment. For this reason, the crowns fabricated with BIM might have a more functionally desirable occlusal surface compared to the crowns fabricated with CIM.

  8. [Comparison of 2 lacrimal punctal occlusion methods].

    PubMed

    Shalaby, O; Rivas, L; Rivas, A I; Oroza, M A; Murube, J

    2001-09-01

    To study and compare two methods for canalicular occlusion: Cautery and Punctal Patch. The study included fourty patients divided in two groups of 20 patients. The end point was 4 occluded puncti. The first group underwent deep cauterization resulting in occlusion of the full vertical aspect of the canaliculus. The second group underwent punctal patch technique for canalicular occlusion. Differential parameters were the following: time of intervention, ease of use, risks and precision. In the post operatory, discomfort, subjective and objective improvement in ocular surface as well as long term result of each technique was analysed. Time of intervention was longer for punctal patch compared to cautery. Both methods exhibited similar ease of use and improvement in ocular surface. Precision was high in punctal patch technique showing complete and final occlusion and no punctum needed reopening, while cautery technique presented 20% rate of reopening intervention. Postoperatory discomfort and irritation were remarkably evident with punctal technique, while minimal in cautery technique. Survival analysis after one year follow up, showed a higher rate of advantages for punctal patch technique over cautery technique.

  9. Use of a novel epidermal harvesting system in resource-poor countries.

    PubMed

    Serena, Thomas; Francius, Adler; Taylor, Cristin; MacDonald, John

    2015-03-01

    The 2010 earthquake in Port-au-Prince, Haiti, highlighted the need for wound care in resource-poor countries. Subsequently, the University of Miami in Florida established one of the first interprofessional wound care centers located at Bernard Mevs Hospital in the central portion of Port-au-Prince, caring for patients with acute and chronic wounds. In 2012, the authors used a novel epidermal harvesting system (CelluTome Epidermal Harvesting System; Kinetic Concepts Inc, San Antonio, Texas) to harvest epithelium to be grafted on 7 patients at the Mevs Hospital with longstanding wounds. Epidermal microblisters were obtained from each patient's thigh using the CelluTome Epidermal Harvesting System. After 35 minutes, microblisters were raised using the device harvester, and an adhesive dressing was inserted into the harvester for transfer to the wound site. In patients with lower-extremity wounds, a 2-layer compression dressing was placed over epidermal grafts. Six of the 7 wounds improved or achieved complete closure in 4 weeks. One of the patients with a 2-year-old thigh wound failed to demonstrate improvement; this may have been secondary to an inability to adequately secure the graft. All donor sites healed without any visible scarring. The authors were able to conclude that epidermal grafting may represent a viable reconstructive option for patients in resource-poor countries.

  10. Topical Apigenin Improves Epidermal Permeability Barrier Homeostasis in Normal Murine Skin by Divergent Mechanisms

    PubMed Central

    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

    2013-01-01

    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 the present study, we first determined whether topical apigenin positively influences permeability barrier homeostasis, 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 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 homeostasis after tape stripping, though 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 up-regulated by apigenin. Finally, both CAMP and mBD3 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. PMID:23489424

  11. Collateral Circulation in Chronic Total Occlusions - an interventional perspective.

    PubMed

    Choo, Gim-Hooi

    2015-09-09

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  12. Acute pancreatitis during sickle cell vaso-occlusive painful crisis.

    PubMed

    Ahmed, Shahid; Siddiqui, Anita K; Siddiqui, Rina K; Kimpo, Miriam; Russo, Linda; Mattana, Joseph

    2003-07-01

    Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease. Copyright 2003 Wiley-Liss, Inc.

  13. Computational evaluation of aortic occlusion and the proposal of a novel, improved occluder: Constrained endo-aortic balloon occlusion.

    PubMed

    de Vaal, M H; Gee, M W; Stock, U A; Wall, W A

    2016-12-01

    Because aortic occlusion is arguably one of the most dangerous aortic manipulation maneuvers during cardiac surgery in terms of perioperative ischemic neurological injury, the purpose of this investigation is to assess the structural mechanical impact resulting from the use of existing and newly proposed occluders. Existing (clinically used) occluders considered include different cross-clamps (CCs) and endo-aortic balloon occlusion (EABO). A novel occluder is also introduced, namely, constrained EABO (CEABO), which consists of applying a constrainer externally around the aorta when performing EABO. Computational solid mechanics are employed to investigate each occluder according to a comprehensive list of functional requirements. The potential of a state of occlusion is also considered for the first time. Three different constrainer designs are evaluated for CEABO. Although the CCs were responsible for the highest strains, largest deformation, and most inefficient increase of the occlusion potential, it remains the most stable, simplest, and cheapest occluder. The different CC hinge geometries resulted in poorer performance of CC used for minimally invasive procedures than conventional ones. CEABO with a profiled constrainer successfully addresses the EABO shortcomings of safety, stability, and positioning accuracy, while maintaining its complexities of operation (disadvantage) and yielding additional functionalities (advantage). Moreover, CEABO is able to achieve the previously unattainable potential to provide a clinically determinable state of occlusion. CEABO offers an attractive alternative to the shortcomings of existing occluders, with its design rooted in achieving the highest patient safety. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Influence of occlusal contact area on cusp defection and stress distribution.

    PubMed

    Costa, Anna Karina Figueiredo; Xavier, Thaty Aparecida; Paes-Junior, Tarcisio José Arruda; Andreatta-Filho, Oswaldo Daniel; Borges, Alexandre Luiz Souto

    2014-11-01

    The purpose of this study was to evaluate the effect of occlusal contact area for loading on the cuspal defection and stress distribution in a first premolar restored with a high elastic modulus restorative material. The Rhinoceros 4.0 software was used for modeling the three-dimensional geometries of dental and periodontal structures and the inlay restoration. Thus, two different models, intact and restored teeth with three occlusal contact areas, 0.1, 0.5 and 0.75 mm(2), on enamel at the occlusal surface of buccal and lingual cusps. Finite element analysis (FEA) was performed with the program ANSYS (Workbench 13.0), which generated a mesh with tetrahedral elements with greater refinement in the regions of interest, and was constrained at the bases of cortical and trabecular bone in all axis and loaded with 100 N normal to each contact area. To analysis of maximum principal stress, the smaller occlusal contact area showed greater compressive stress in region of load application for both the intact and inlay restored tooth. However, tensile stresses at the occlusal isthmus were similar for all three tested occlusal contact areas (60 MPa). To displacement of the cusps was higher for teeth with inlay (0.46-0.48 mm). For intact teeth, the smaller contact area showed greater displacement (0.10 mm). For teeth with inlays, the displacement of the cusps were similar in all types of occlusal area. Cuspal displacement was higher in the restored tooth when compared to the intact tooth, but there were no significant variations even with changes in the occlusal contact area. RELEVANCE CLINICAL: Occlusal contacts have a great influence on the positioning of teeth being able to maintain the position and stability of the mandible. Axial loads would be able to generate more uniform stress at the root presenting a greater concentration of load application in the point and the occlusal surface. Thus, is necessary to analyze the relationship between these occlusal contacts as dental

  15. Occludin is regulated by epidermal growth factor receptor activation in brain endothelial cells and brains of mice with acute liver failure.

    PubMed

    Chen, Feng; Hori, Tomohide; Ohashi, Norifumi; Baine, Ann-Marie; Eckman, Christopher B; Nguyen, Justin H

    2011-04-01

    Mechanisms of brain edema in acute liver failure (ALF) are not completely understood. We recently demonstrated that matrix metalloproteinase 9 (MMP-9) induces significant alterations to occludin in brain endothelial cells in vitro and in brains of mice with experimental ALF (Hepatology 2009;50:1914). In this study we show that MMP-9-induced transactivation of epidermal growth factor receptor (EGFR) and p38 MAPK/NFκB (mitogen-activated protein kinase/nuclear factor-kappa B) signals participate in regulating brain endothelial occludin level. Mouse brain endothelial bEnd3 cells were exposed to MMP-9 or p38 MAPK up-regulation in the presence and absence of EGFR inhibitor, p38 MAPK inhibitor, NFκB inhibitor, and/or appropriate small interfering RNA. Reverse-transcription polymerase chain reaction (RT-PCR) and western blotting were used for messenger RNA and protein expression analyses. Immunohistochemical staining and confocal microscopy were used to demonstrate cellular EGFR activation. Intraperitoneal azoxymethane was use to induce ALF in mice. Brains of comatose ALF mice were processed for histological and biochemical analyses. When bEnd3 cells were exposed to MMP-9, EGFR was significantly transactivated, followed by p38 MAPK activation, I-kappa B alpha (IκBα) degradation, NFκB activation, and suppression of occludin synthesis and expression. Similar EGFR activation and p38 MAPK/NFκB activation were found in the brains of ALF mice, and these changes were attenuated with GM6001 treatment. EGFR activation with p38 MAPK/NFκB signaling contributes to the regulation of tight junction integrity in ALF. EGFR activation may thus play an important role in vasogenic brain edema in ALF. 2011 American Association for the Study of Liver Diseases.

  16. Venous sinus occlusive disease: MR findings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yuh, W.T.C.; Simonson, T.M.; Tali, E.T.

    1994-02-01

    To study MR patterns of venous sinus occlusive disease and to relate them to the underlying pathophysiology by comparing the appearance and pathophysiologic features of venous sinus occlusive disease with those of arterial ischemic disease. The clinical data and MR examinations of 26 patients with venous sinus occlusive disease were retrospectively reviewed with special attention to mass effect, hemorrhage, and T2-weighted image abnormalities as well as to abnormal parenchymal, venous, or arterial enhancement after intravenous gadopentetate dimeglumine administration. Follow-up studies when available were evaluated for atrophy, infraction, chronic mass effect, and hemorrhage. Mass effect was present in 25 of 26more » patients. Eleven of the 26 had mass effect without abnormal signal on T2-weighted images. Fifteen patients had abnormal signal on T2-weighted images, but this was much less extensive than the degree of brain swelling in all cases. No patient showed abnormal parenchymal or arterial enhancement. Abnormal venous enhancement was seen in 10 of 13 patients who had contrast-enhanced studies. Intraparenchymal hemorrhage was seen in nine patients with high signal on T2-weighted images predominantly peripheral to the hematoma in eight. Three overall MR patterns were observed in acute sinus thrombosis: (1) mass effect without associated abnormal signal on T2-weighted images, (2) mass effect with associated abnormal signal on T2-weighted images and/or ventricular dilatation that may be reversible, and (3) intraparenchymal hematoma with surrounding edema. MR findings of venus sinus occlusive disease are different from those of arterial ischemia and may reflect different underlying pathophysiology. In venous sinus occlusive disease, the breakdown of the blood-brain barrier (vasogenic edema and abnormal parenchymal enhancement) does not always occur, and brain swelling can persist up to 2 years with or without abnormal signal on T2-weighted images. 34 refs., 5 figs.« less

  17. Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.

    PubMed

    Chamcheu, Jean Christopher; Afaq, Farrukh; Syed, Deeba N; Siddiqui, Imtiaz A; Adhami, Vaqar M; Khan, Naghma; Singh, Sohinderjit; Boylan, Brendan T; Wood, Gary S; Mukhtar, Hasan

    2013-05-01

    Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses. © 2013 John Wiley & Sons A/S.

  18. The receptor tyrosine kinase ERBB4 is expressed in skin keratinocytes and influences epidermal proliferation.

    PubMed

    Hoesl, Christine; Röhrl, Jennifer M; Schneider, Marlon R; Dahlhoff, Maik

    2018-04-01

    The epidermal growth factor receptor (EGFR) and associated receptors ERBB2 and ERBB3 are important for skin development and homeostasis. To date, ERBB4 could not be unambiguously identified in the epidermis. The aim of this study was to analyze the ERBB-receptor family with a special focus on ERBB4 in vitro in human keratinocytes and in vivo in human and murine epidermis. We compared the transcript levels of all ERBB-receptors and the seven EGFR-ligands in HaCaT and A431 cells. ERBB-receptor activity was analyzed after epidermal growth factor (EGF) stimulation by Western blot analysis. The location of the receptors was investigated by immunofluorescence in human keratinocytes and skin. Finally, we investigated the function of ERBB4 in the epidermis of skin-specific ERBB4-knockout mice. After EGF stimulation, all ligands were upregulated except for epigen. Expression levels of EGFR were unchanged, but all other ERBB-receptors were down-regulated after EGF stimulation, although all ERBB-receptors were phosphorylated. We detected ERBB4 at mRNA and protein levels in both human epidermal cell lines and in the basal layer of human and murine epidermis. Skin-specific ERBB4-knockout mice revealed a significantly reduced epidermal thickness with a decreased proliferation rate. ERBB4 is expressed in the basal layer of human epidermis and cultured keratinocytes as well as in murine epidermis. Moreover, ERBB4 is phosphorylated in HaCaT cells due to EGF stimulation, and its deletion in murine epidermis affects skin thickness by decreasing proliferation. ERBB4 is expressed in human keratinocytes and plays a role in murine skin homeostasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Compliance with the prescribed occlusion treatment for amblyopia.

    PubMed

    Vagge, Aldo; Nelson, Leonard B

    2017-09-01

    The present review article is an update on the current evidence about compliance to the prescribed occlusion treatment for amblyopia. In particular, the authors focus on the predictors and causes of noncompliance and possible interventions to increase it. Compliance with prescribed occlusion treatment is often challenging. Reported rates of compliance range widely from 49% to 87%. Objective monitoring of occlusion has opened up new research opportunities and allow the design of effective therapeutic regimens. Also, predictors and causes of noncompliance have been investigated and their knowledge may help the clinician to improved compliance with prescribed occlusion treatment for amblyopia. Although many of the studies assessing the effectiveness of interventions to increase compliance to patching treatment for amblyopia have many limitations, evidences support that use of educational supports, parents, and patient understanding on the importance of patching and written information should be considered to increase compliance with patching.

  20. Automated vision occlusion-timing instrument for perception-action research.

    PubMed

    Brenton, John; Müller, Sean; Rhodes, Robbie; Finch, Brad

    2018-02-01

    Vision occlusion spectacles are a highly valuable instrument for visual-perception-action research in a variety of disciplines. In sports, occlusion spectacles have enabled invaluable knowledge to be obtained about the superior capability of experts to use visual information to guide actions within in-situ settings. Triggering the spectacles to occlude a performer's vision at a precise time in an opponent's action or object flight has been problematic, due to experimenter error in using a manual buttonpress approach. This article describes a new laser curtain wireless trigger for vision occlusion spectacles that is portable and fast in terms of its transmission time. The laser curtain can be positioned in a variety of orientations to accept a motion trigger, such as a cricket bowler's arm that distorts the lasers, which then activates a wireless signal for the occlusion spectacles to change from transparent to opaque, which occurs in only 8 ms. Results are reported from calculations done in an electronics laboratory, as well as from tests in a performance laboratory with a cricket bowler and a baseball pitcher, which verified this short time delay before vision occlusion. In addition, our results show that occlusion consistently occurred when it was intended-that is, near ball release and during mid-ball-flight. Only 8% of the collected data trials were unusable. The laser curtain improves upon the limitations of existing vision occlusion spectacle triggers, indicating that it is a valuable instrument for perception-action research in a variety of disciplines.

  1. Virtual occlusal definition for orthognathic surgery.

    PubMed

    Liu, X J; Li, Q Q; Zhang, Z; Li, T T; Xie, Z; Zhang, Y

    2016-03-01

    Computer-assisted surgical simulation is being used increasingly in orthognathic surgery. However, occlusal definition is still undertaken using model surgery with subsequent digitization via surface scanning or cone beam computed tomography. A software tool has been developed and a workflow set up in order to achieve a virtual occlusal definition. The results of a validation study carried out on 60 models of normal occlusion are presented. Inter- and intra-user correlation tests were used to investigate the reproducibility of the manual setting point procedure. The errors between the virtually set positions (test) and the digitized manually set positions (gold standard) were compared. The consistency in virtual set positions performed by three individual users was investigated by one way analysis of variance test. Inter- and intra-observer correlation coefficients for manual setting points were all greater than 0.95. Overall, the median error between the test and the gold standard positions was 1.06mm. Errors did not differ among teeth (F=0.371, P>0.05). The errors were not significantly different from 1mm (P>0.05). There were no significant differences in the errors made by the three independent users (P>0.05). In conclusion, this workflow for virtual occlusal definition was found to be reliable and accurate. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Penile epidermal inclusion cyst: a late complication of penile girth enhancement surgery.

    PubMed

    Park, Hyun Jun; Park, Nam Cheol; Park, Sung Woo; Jern, Tae Kyung; Choi, Kyung-Un

    2008-09-01

    Epidermal inclusion cysts are benign lesions that can develop in any part of the body. However, the finding of an epidermal inclusion cyst in the penis is rare. The aim of this article was to present the management of a case of a penile epidermal inclusion cyst that occurred because of late complications of a penile girth enhancement surgery. A 52-year-old man presented with a painless, slowly growing mass in the penis, which was first noted after a penile girth enhancement surgery 20 years ago. A cystic mobile mass about 2 cm in depth was found surrounding the coronal sulcus. Excision of the mass was performed for diagnosis and treatment. There was no communication with the urethra. The pathological diagnosis was an epidermal inclusion cyst of the penis. A penile epidermal inclusion cyst in adult men is rare. It can develop after an inadequate procedure for penile girth enhancement, and should be treated by complete resection.

  3. Apoptosis as a Mechanism for Keratinocyte Death in Canine Toxic Epidermal Necrolysis.

    PubMed

    Banovic, F; Dunston, S; Linder, K E; Rakich, P; Olivry, T

    2017-03-01

    In humans and dogs, toxic epidermal necrolysis (TEN) is a life-threatening dermatosis characterized by sudden epidermal death resulting in extensive skin detachment. There is little information on the pathogenesis of keratinocyte cell death in canine TEN. We studied the occurrence of apoptosis in skin lesions of dogs with TEN to determine if apoptosis contributes to the pathogenesis of this disease. Immunostaining with antibodies to activated caspase-3 and the terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique revealed positive apoptotic keratinocytes in basal and suprabasal epidermal compartments in 17 biopsy specimens collected from 3 dogs with TEN and 16 from 3 dogs with erythema multiforme (EM). There was no significant difference in the number of positively stained epidermal cells between TEN and EM. These results suggest that apoptosis of epidermal keratinocytes and lymphocytic satellitosis represent one of the early steps in the pathogenesis of canine TEN, as in the human disease counterpart.

  4. Indirubin, an acting component of indigo naturalis, inhibits EGFR activation and EGF-induced CDC25B gene expression in epidermal keratinocytes.

    PubMed

    Hsieh, Wan-Ling; Lin, Yin-Ku; Tsai, Chi-Neu; Wang, Ta-Min; Chen, Tzu-Ya; Pang, Jong-Hwei S

    2012-08-01

    Topical indigo naturalis ointment is clinically proved to be an effective therapy for plaque-type psoriasis. Indirubin, as the active component of indigo naturalis, inhibits cell proliferation of epidermal keratinocytes. However, the detailed underlying mechanism is not fully understood. To further investigate the anti-proliferating effects of indigo naturalis and indirubin on epidermal keratinocytes. The decreased expression of CDC25B in indigo naturalis- or indirubin-treated epidermal keratinocytes, as revealed by cDNA microarray analysis, was studied. The CDC25B expression was examined under different serum concentrations and compared between primary and immortalized keratinocytes. The activation of EGFR and the effect of EGF on the cell proliferation and CDC25B expression were also investigated in epidermal keratinocytes. RT/real-time PCR and western blot method were used to analyze the CDC25B expression at the mRNA and protein levels, respectively. Indigo naturalis and indirubin were confirmed to down-regulate CDC25B expression significantly at both the mRNA and protein levels. The growth-dependent expression of CDC25B was demonstrated by the increased expression in serum-stimulated and immortalized keratinocytes. The activation of EGF receptor, known to be highly expressed in psoriatic lesions, was inhibited by indigo naturalis or indirubin. The cell proliferation and CDC25B expression of epidermal keratinocytes were induced by EGF alone and confirmed to be inhibited by indigo naturalis or indirubin. Except being a common therapeutic target in various cancers, CDC25B also plays an important role in the hyper-proliferation of epidermal keratinocytes which can be suppressed by anti-psoriatic drug indigo naturalis and its component, indirubin. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. On the relevance of "ideal" occlusion concepts for incisor inclination target definition.

    PubMed

    Knösel, Michael; Jung, Klaus

    2011-11-01

    The concept of "ideal" occlusion in harmony with craniofacial structures is often proposed as an ultimate goal of orthodontic treatment. The aim of this study was to assess the impact of slight variations in posterior occlusion and the history of straight-wire orthodontic treatment on the predictability of incisor inclination and third-order angles. Axial incisor inclinations, third-order angles, and craniofacial relationships were assessed on lateral headfilms and corresponding dental casts of 75 healthy white subjects, 16 to 26 years old, selected by the general inclusion criterion of a good interincisal relationship. Four groups were formed: group A (n = 17), Angle Class I occlusion subjects with no orthodontic treatment; group B (n = 20), Angle Class I occlusion subjects treated with standardized straight-wire orthodontics; group C (n = 20), up to a half-cusp distal occlusion after straight-wire treatment; and group D (n = 18), up to a half-cusp distal occlusion and no orthodontic treatment. Regression analysis was used to insert predictor angles into selected regression equations of the subjects with "ideal" occlusion, and the absolute differences between predicted and observed response angles were determined. Small differences in incisor inclination were found between subjects with "ideal" occlusion and those who slightly deviated from "ideal" with a mild occlusion of the Angle Class II category. Posterior occlusion was not relevant to the validity of the vast majority of predictor-response pairs. Straight-wire treatment produced incisor inclination that was slightly protruded compared with subjects who had good natural occlusion. The "ideal" posterior occlusion concepts as a general orthodontic treatment goal should be reconsidered. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  6. Extravasal occlusion of large vessels with titanic clips: efficiency, indications, and contraindications.

    PubMed

    Vasilenko, Yu V; Kim, A I; Kotov, S A

    2002-11-01

    The mechanism of extravasal occlusion of blood vessels with titanic clips "Atrauclip" and "Ligaclip extra" was studied in order to reveal indications and contraindications to their use. Occlusion with the clips of both types was ineffective in vessels with a diameter of >7.0 mm. Arteritis or the presence of an intravascular occlusion facility in the vessel were also the contraindications for clip occlusion. In overcases the procedure of occlusion with titanic clips was efficient and atraumatic.

  7. Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

    PubMed Central

    Arima, Kazuhiko; Ohta, Shoichiro; Takagi, Atsushi; Shiraishi, Hiroshi; Masuoka, Miho; Ontsuka, Kanako; Suto, Hajime; Suzuki, Shoichi; Yamamoto, Ken-ichi; Ogawa, Masahiro; Simmons, Olga; Yamaguchi, Yukie; Toda, Shuji; Aihara, Michiko; Conway, Simon J.; Ikeda, Shigaku; Izuhara, Kenji

    2016-01-01

    Background Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis. Methods To examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin’s role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ). Results Periostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, –22, or –23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells. Conclusions Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis. PMID:25572557

  8. Mechanism of vaso-occlusion in sickle cell anemia

    NASA Astrophysics Data System (ADS)

    Lei, Huan; Karniadakis, George

    2012-11-01

    Vaso-occlusion crisis is one of the key hallmark of sickle cell anemia. While early studies suggested that the crisis is caused by blockage of a single elongated cell, recent experimental investigations indicate that vaso-occlusion is a complex process triggered by adhesive interactions among different cell groups in multiple stages. Based on dissipative particle dynamics, a multi-scale model for the sickle red blood cells (SS-RBCs), accounting for diversity in both shapes and cell rigidities, is developed to investigate the mechanism of vaso-occlusion crisis. Using this model, the adhesive dynamics of single SS-RBC was investigated in arterioles. Simulation results indicate that the different cell groups (deformable SS2 RBCs, rigid SS4 RBCs, leukocytes, etc.) exhibit heterogeneous adhesive behavior due to the different cell morphologies and membrane rigidities. We further simulate the tube flow of SS-RBC suspensions with different cell fractions. The more adhesive SS2 cells interact with the vascular endothelium and further trap rigid SS4 cells, resulting in vaso-occlusion in vessels less than 15 μm . Under inflammation, adherent leukocytes may also trap SS4 cells, resulting in vaso-occlusion in even larger vessels. This work was supported by the NSF grant CBET-0852948 and the NIH grant R01HL094270.

  9. Linear Cowden nevus: a new distinct epidermal nevus.

    PubMed

    Happle, Rudolf

    2007-01-01

    Within the group of epidermal nevi, a so far nameless disorder is described under the term "linear Cowden nevus". This non-organoid epidermal nevus is caused by loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. Hence, linear Cowden nevus can be categorized as a characteristic feature of type 2 segmental Cowden disease. Until now, several authors had mistaken this epidermal nevus as a manifestation of Proteus syndrome. The concept of linear Cowden nevus implies that Proteus syndrome is by no means caused by PTEN mutations. As a clinical difference, linear Cowden nevus is markedly papillomatous and thick, whereas linear Proteus nevus tends to be rather flat. Moreover, the spectrum of possibly associated cutaneous or extracutaneous anomalies differs in the two types of nevi. In conclusion, linear Cowden nevus, that may also be called "linear PTEN nevus", represents a distinct clinicogenetic entity.

  10. Evaluation of Carbon Dioxide Laser in the Treatment of Epidermal Nevi.

    PubMed

    Bhat, Yasmeen Jabeen; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Mubashir, Syed; Akhter, Saniya; Wani, Roohi

    2016-01-01

    Epidermal naevi are benign hamartomatous growths of the skin which are generally asymptomatic with a benign course but are cosmetically disagreeable. Topical treatments such as steroids, calcipotriol, 5 fluorouracil, podophyllin, retinoids and cryotherapy are ineffective and surgical excision results in scar formation. Therapy is often challenging. To study the response of carbon dioxide (CO 2 ) laser in the management of epidermal naevi. We conducted a study of CO 2 laser treatment on 15 patients of epidermal naevi, eight with verrucous epidermal naevi and seven with sebaceous naevi. A thorough history and examination was done to rule out any epidermal naevus syndrome. The diagnosis was confirmed by histopathology. The number of treatment sessions varied from 1 to 8. Response was excellent (>90% reduction in lesion size) in three patients, very good (>75% reduction) in five, good (>50% reduction in lesion size) in five and poor (<50% reduction in lesion size) in two patients. The side effects were hyperpigmentation and scarring. Long-term follow-up over a period of 10 months showed a recurrence rate of 20%. We conclude that CO 2 laser treatment might be an effective option with long-term safety, minimal discomfort and rapid recovery.

  11. Analysis of E2F factors during epidermal differentiation.

    PubMed

    Chang, Wing Y; Dagnino, Lina

    2005-01-01

    The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

  12. Occlusal tooth wear in Chinese adults with shortened dental arches.

    PubMed

    Zhang, Q; Witter, D J; Bronkhorst, E M; Bartlett, D W; Creugers, N H J

    2014-02-01

    To assess associations between occlusal tooth wear and shortened dental arches (SDA) in Chinese 40 years and older subjects. From a sample of 1462 urban and rural adults, those presenting with SDA (n = 150) were compared with a control group of 65 randomly selected subjects with complete dentitions (CDA). Occlusal wear was assessed using a modified Smith and Knight index - the occlusal tooth wear index (OWTI) - and analysed using multivariate (logistic) regression. There was no significant effect from SDA on severe occlusal wear (OTWI score 3 or 4: OR = 2.016; 95% CI = 0.960-4.231; P = 0.064). Higher age was associated with severe occlusal wear (P values ≤0.007) and with higher mean OTWI scores; urban had less often severe occlusal wear than rural residents (OR = 0.519; P = 0.008). Higher mean OTWI scores were associated with rural residents, except for anterior teeth. Females had lower mean OTWI score for anterior teeth (effect = -0.153; P = 0.030). Premolars in SDA had higher mean OTWI scores compared with those in CDA (effect = +0.213; P = 0.006). In SDA, more posterior occluding pairs (POPs) were associated with lower mean OTWI sores for anterior teeth (effect: -0.158; P = 0.008) and higher scores for molars (effect: +0.249, P = 0.003). Subjects with SDA or CDA presented comparable occlusal wear, but premolars in SDA tend to have higher probability for having occlusal wear. Fewer numbers of POPs were associated with more wear in anterior teeth. © 2013 John Wiley & Sons Ltd.

  13. Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

    PubMed

    Ortiz-Bautista, Carlos; Hernández-González, Ignacio; Escribano-Subías, Pilar

    2017-03-22

    Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension which is part, together with pulmonary capillary hemangiomatosis, of the special designation (subgroup 1') within pulmonary hypertension group 1 in the latest classification of the pulmonary hypertension World Symposium. Recent discovery that gene mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) are responsible for inherited forms of pulmonary veno-occlusive disease has changed the role of genetic testing, acquiring relevant importance in the diagnosis of these patients. Despite the advances in genetic, cellular and molecular basis knowledge in the last decade, pulmonary veno-occlusive disease remains as a rare aetiology of pulmonary hypertension without any effective medical treatment approved and poor outcomes. This document aims to review the advances occurred in the understanding of pulmonary veno-occlusive disease in the last years. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. A change in humidification system can eliminate endotracheal tube occlusion.

    PubMed

    Doyle, Alex; Joshi, Manasi; Frank, Peter; Craven, Thomas; Moondi, Parvez; Young, Peter

    2011-12-01

    Inadequate airway humidification can result in endotracheal tube occlusion. There is evidence that heat and moisture exchangers (HMEs) are more prone to endotracheal tube occlusion than heated humidifiers (HHs) that contain a heated wire circuit. We aimed to compare the incidence of endotracheal tube occlusion while introducing a new dual-heated wire circuit HH in place of an established hydrophobic HME. This was a prospective observational study. All patients who required intubation were included in our analysis. Univariate statistical analysis was performed using a Fisher exact test. P < .05 was considered statistically significant. There were 158 patients in the HME group and 88 patients in the HH group. The incidence of endotracheal tube occlusion was 5.7% in the HME group and 0% in the HH group. Statistical analysis revealed a significant difference between the 2 groups (P = .02). In light of this finding, we changed our practice to provide humidification exclusively by HH. In the subsequent 18-month period, there were no further episodes of endotracheal tube occlusion. Our study demonstrates that there is a significant increase in the incidence of endotracheal tube occlusion when using a hydrophobic HME compared with an HH and that using a dual-heated wire circuit HH can eliminate endotracheal tube occlusion. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Does partial occlusion promote normal binocular function?

    PubMed

    Li, Jingrong; Thompson, Benjamin; Ding, Zhaofeng; Chan, Lily Y L; Chen, Xiang; Yu, Minbin; Deng, Daming; Hess, Robert F

    2012-10-03

    There is growing evidence that abnormal binocular interactions play a key role in the amblyopia syndrome and represent a viable target for treatment interventions. In this context the use of partial occlusion using optical devices such as Bangerter filters as an alternative to complete occlusion is of particular interest. The aims of this study were to understand why Bangerter filters do not result in improved binocular outcomes compared to complete occlusion, and to compare the effects of Bangerter filters, optical blur and neutral density (ND) filters on normal binocular function. The effects of four strengths of Bangerter filters (0.8, 0.6, 0.4, 0.2) on letter and vernier acuity, contrast sensitivity, stereoacuity, and interocular suppression were measured in 21 observers with normal vision. In a subset of 14 observers, the partial occlusion effects of Bangerter filters, ND filters and plus lenses on stereopsis and interocular suppression were compared. Bangerter filters did not have graded effect on vision and induced significant disruption to binocular function. This disruption was greater than that of monocular defocus but weaker than that of ND filters. The effect of the Bangerter filters on stereopsis was more pronounced than their effect on monocular acuity, and the induced monocular acuity deficits did not predict the induced deficits in stereopsis. Bangerter filters appear to be particularly disruptive to binocular function. Other interventions, such as optical defocus and those employing computer generated dichoptic stimulus presentation, may be more appropriate than partial occlusion for targeting binocular function during amblyopia treatment.

  16. Occlusal accommodation and mouthguards for prevention of orofacial trauma.

    PubMed

    Geary, Julian Lindsay; Clifford, Thomas Joseph; Kinirons, Martin James

    2009-01-01

    The aim of this study was to investigate the effect of two types of occlusal accommodation on the arch separation in centric and eccentric arch positions and to assess the opposing tooth contacts in professionally made, thermoformed sports mouthguards. Maxillary and mandibular alginate impressions, a wax interocclusal record of centric occlusion together with maxillary/condylar face-bow registrations, were recorded clinically for 10 undergraduate dental students who are sports activist volunteers of the School of Medicine and Dentistry, Queen's University Belfast. Two ethylene vinyl acetate thermoformed maxillary mouthguards were made for each player (N = 20) using a standardised procedure. Ten mouthguards served both as the control (i.e. the non-accommodated) group and also the accommodated, occlusally 'imprinted' group. The other 10 mouthguards served as the accommodated, occlusally 'ground' group. Casts were articulated, each non-accommodated and accommodated mouthguard was seated and the extent of the interocclusal opening was recorded in all three arch relationships. The number of mouthguard and mandibular tooth contacts were also recorded in each position. The increased vertical occlusal dimension that was found in the presence of non-accommodated mouthguards equated to the full-sheet thickness of the material that was used to form the mouthguards. Only mouthguards accommodated by grinding retained high levels of occlusal contact in all arch relationships that were tested. Within the limitations of this study, the modification of the occlusal surface made by flat grinding reduced the arch separation in eccentric movements and increased the opposing tooth contacts in custom-made mouthguards. This may contribute to increased comfort, compliance and the protective effect of these appliances thus resulting in a reduction of injuries to the teeth, arches and soft tissues.

  17. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    PubMed Central

    Kothari, Mihir

    2014-01-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa. PMID:23571255

  18. Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

    PubMed

    Kothari, Mihir

    2014-12-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  19. Role of milk fat globule-epidermal growth factor 8 in osteoimmunology

    PubMed Central

    Sinningen, Kathrin; Thiele, Sylvia; Hofbauer, Lorenz C; Rauner, Martina

    2016-01-01

    Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that is abundantly expressed in various tissues and has a pivotal role in the phagocytic clearance of apoptotic cells. However, MFG-E8 has also gained significant attention because of its wide range of functions in autoimmunity, inflammation and tissue homeostasis. More recently, MFG-E8 has been identified as a critical regulator of bone homeostasis, being expressed in both, osteoblasts and osteoclasts. In addition, it was shown that MFG-E8 fulfils an active role in modulating inflammatory processes, suggesting an anti-inflammatory role of MFG-E8 and proposing it as a novel therapeutic target for inflammatory diseases. This concise review focusses on the expression and regulation of MFG-E8 in the context of inflammatory bone diseases, highlights its role in the pathophysiology of osteoimmune diseases and discusses the therapeutic potential of MFG-E8. PMID:27579162

  20. Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity.

    PubMed

    Coca, Mircea; Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

    2017-08-23

    We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise.

  1. Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity

    PubMed Central

    Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

    2017-01-01

    We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise. PMID:29067224

  2. Occludin is regulated by epidermal growth factor receptor activation in brain endothelial cells and brains of mice with acute liver failure

    PubMed Central

    Chen, Feng; Hori, Tomohide; Ohashi, Norifumi; Baine, Ann-Marie; Eckman, Christopher B.; Nguyen, Justin H.

    2011-01-01

    Mechanisms of brain edema in acute liver failure (ALF) are not completely understood. We recently demonstrated that matrix metalloproteinase 9 (MMP-9) induces significant alterations to occludin in brain endothelial cells in vitro and in brains of mice with experimental ALF (Hepatology 50:1914, 2009). In this study, we show that MMP-9-induced transactivation of epidermal growth factor receptor (EGFR) and p38MAPK/NFκB signals participate in regulating brain endothelial occludin level. Mouse brain endothelial bEnd3 cells were exposed to MMP-9 or p38 MAPK upregulation in the presence and absence of EGFR inhibitor, p38 MAPK inhibitor, NFκB inhibitor, and/or appropriate small interfering RNA. RT-PCR and western blotting were used for mRNA and protein expression analyses. Immunohistochemical staining and confocal microscopy were used to demonstrate cellular EGFR activation. Intraperitoneal azoxymethane was use to induce ALF in mice. Brains of comatose ALF mice were processed for histological and biochemical analyses. When bEnd3 cells were exposed to MMP-9, EGFR was significantly transactivated, followed by p38 MAPK activation, IκBα degradation, NFκB activation, and suppression of occludin synthesis and expression. Similar EGFR activation and p38 MAPK/NFκB activation were found in the brains of ALF mice, and these changes were attenuated with GM6001 treatment. Conclusion EGFR activation with p38 MAPK/NFκB signaling contributes to the regulation of tight junction integrity in ALF. EGFR activation may thus play an important role in vasogenic brain edema in ALF. PMID:21480332

  3. 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.

  4. Prosthetic occlusive device for an internal passageway

    NASA Technical Reports Server (NTRS)

    Tenney, J. B., Jr. (Inventor)

    1983-01-01

    An occlusive device is disclosed for surgical implant to occlude the lumen of an internal organ. The device includes a cuff having a backing collar and two isolated cuff chambers. The fluid pressure of one chamber is regulated by a pump/valve reservoir unit. The other chamber is unregulated in pressure but its fluid volume is adjusted by removing or adding fluid to a septum/reservoir by means of a hypodermic needle. Pressure changes are transmitted between the two cuff chambers via faying surfaces which are sufficiently large in contact area and thin as to transmit pressure generally without attenuation. By adjusting the fluid volume of the septum, the operating pressure of the device may be adjusted to accommodate tubular organs of different diameter sizes as well as to compensate for changes in the organ following implant without reoperation.

  5. Improving prediction of recanalization in acute large-vessel occlusive stroke.

    PubMed

    Vanacker, P; Lambrou, D; Eskandari, A; Maeder, P; Meuli, R; Ntaios, G; Michel, P

    2014-06-01

    Recanalization in acute ischemic stroke with large-vessel occlusion is a potent indicator of good clinical outcome. To identify easily available clinical and radiologic variables predicting recanalization at various occlusion sites. All consecutive, acute stroke patients from the Acute STroke Registry and Analysis of Lausanne (2003-2011) who had a large-vessel occlusion on computed tomographic angiography (CTA) (< 12 h) were included. Recanalization status was assessed at 24 h (range: 12-48 h) with CTA, magnetic resonance angiography, or ultrasonography. Complete and partial recanalization (corresponding to the modified Treatment in Cerebral Ischemia scale 2-3) were grouped together. Patients were categorized according to occlusion site and treatment modality. Among 439 patients, 51% (224) showed complete or partial recanalization. In multivariate analysis, recanalization of any occlusion site was most strongly associated with endovascular treatment, including bridging therapy (odds ratio [OR] 7.1, 95% confidence interval [CI] 2.2-23.2), and less so with intravenous thrombolysis (OR 1.6, 95% CI 1.0-2.6) and recanalization treatments performed beyond guidelines (OR 2.6, 95% CI 1.2-5.7). Clot location (large vs. intermediate) and tandem pathology (the combination of intracranial occlusion and symptomatic extracranial stenosis) were other variables discriminating between recanalizers and non-recanalizers. For patients with intracranial occlusions, the variables significantly associated with recanalization after 24 h were: baseline National Institutes of Health Stroke Scale (NIHSS) (OR 1.04, 95% CI 1.02-1.1), Alberta Stroke Program Early CT Score (ASPECTS) on initial computed tomography (OR 1.2, 95% CI 1.1-1.3), and an altered level of consciousness (OR 0.2, 95% CI 0.1-0.5). Acute endovascular treatment is the single most important factor promoting recanalization in acute ischemic stroke. The presence of extracranial vessel stenosis or occlusion decreases

  6. Evaluation of Carbon Dioxide Laser in the Treatment of Epidermal Nevi

    PubMed Central

    Bhat, Yasmeen Jabeen; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Mubashir, Syed; Akhter, Saniya; Wani, Roohi

    2016-01-01

    Background: Epidermal naevi are benign hamartomatous growths of the skin which are generally asymptomatic with a benign course but are cosmetically disagreeable. Topical treatments such as steroids, calcipotriol, 5 fluorouracil, podophyllin, retinoids and cryotherapy are ineffective and surgical excision results in scar formation. Therapy is often challenging. Aim of the Study: To study the response of carbon dioxide (CO2) laser in the management of epidermal naevi. Subjects and Methods: We conducted a study of CO2 laser treatment on 15 patients of epidermal naevi, eight with verrucous epidermal naevi and seven with sebaceous naevi. A thorough history and examination was done to rule out any epidermal naevus syndrome. The diagnosis was confirmed by histopathology. The number of treatment sessions varied from 1 to 8. Results: Response was excellent (>90% reduction in lesion size) in three patients, very good (>75% reduction) in five, good (>50% reduction in lesion size) in five and poor (<50% reduction in lesion size) in two patients. The side effects were hyperpigmentation and scarring. Long-term follow-up over a period of 10 months showed a recurrence rate of 20%. Conclusion: We conclude that CO2 laser treatment might be an effective option with long-term safety, minimal discomfort and rapid recovery. PMID:27761089

  7. Phacomatosis pigmentokeratotica: another epidermal nevus syndrome and a distinctive type of twin spotting.

    PubMed

    Boente, M C; Pizzi de Parra, N; Larralde de Luna, M; Bonet, H B; Santos Muñoz, A; Parra, V; Gramajo, P; Moreno, S; Asial, R A

    2000-01-01

    The name epidermal nevus syndrome could be applied to a group of clinically and histopathologically different entities as has been pointed out by Happle. Phacomatosis pigmentokeratotica is a further type of epidermal nevus syndrome distinguished by the presence of a sebaceous nevus and a contralateral speckled lentiginous nevus of the papular type, associated with skeletal or neurological abnormalities. Three new cases of this recently delineated syndrome are presented. A common origin may account for the temporal and spatial relationship between the epidermal and the speckled lentiginous nevus. The concept of melanocytic-epidermal twin spotting similar to the interpretation of vascular twin spotting could explain the pathogenesis of this entity.

  8. 21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

  9. 21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

  10. 21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

  11. 21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

  12. 21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

  13. Epidermal Growth Factor Increases LRF/Pokemon Expression in Human Prostate Cancer Cells

    PubMed Central

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K.

    2011-01-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. PMID:21640721

  14. Levodopa-carbidopa with occlusion in older children with amblyopia.

    PubMed

    Bhartiya, Prashant; Sharma, Pradeep; Biswas, Nihar R; Tandon, Radhika; Khokhar, Sudarshan K

    2002-12-01

    To study the role of levodopa-carbidopa in supplementing occlusion therapy in older children with strabismic or anisometropic amblyopia. A clinical study was performed on 40 amblyopic children (19 strabismic and 21 anisometropic), 6 to 18 years old (mean age, 10.9 years). They received an average dose of 1.86 mg/kg/day (1.33-2.36 mg/kg/day) of levodopa and carbidopa (4:1 ratio) or a placebo in 3 divided doses over a 4-week period, combined with full-time occlusion. The occlusion was continued for the study duration of 3 months. Early Treatment Diabetic Retinopathy Study visual acuity charts and Cambridge low-contrast gratings for contrast sensitivity (CS) were used to assess visual functions. Tolerance and compliance with occlusion and capsule consumption were assessed. Visual acuity of the nonamblyopic eye did not deteriorate during the study in either group. CS decreased by 22 units in the levodopa group and increased in the placebo group by 53 units at the first month. The CS in the levodopa group recovered later by the third month of follow-up. Both the levodopa and the placebo groups showed significant improvement in visual function in the amblyopic eye (P <.001). Overall changes in logarithm of minimum angle of resolution values and CS in the amblyopic eyes were similar in both groups (P >.05). Strabismic and anisometropic amblyopes did not behave differently. Drug tolerance, occlusion compliance, and capsule ingestion compliance were similar between the groups, with no significant side effects. Clinically, levodopa supplementation does not offer any advantage over occlusion alone. Moreover, the risk of occlusion amblyopia could increase with the use of drugs like levodopa that might affect the plasticity of the visual cortex.

  15. Hypothalamic digoxin, hemispheric chemical dominance, and mesenteric artery occlusion.

    PubMed

    Kurup, Ravi Kumar; Kurup, Paramesware Achutha

    2003-12-01

    The role of the isoprenoid pathway in vascular thrombosis, especially mesenteric artery occlusion and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with mesenteric artery occlusion and individuals with right hemispheric, left hemispheric, and bihemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition. In patients with mesenteric artery occlusion there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, low ubiquinone, and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and reduction in tyrosine catabolites in the serum. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these patients. The biochemical patterns obtained in mesenteric artery occlusion is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with mesenteric artery occlusion were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Mesenteric artery occlusion occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance may thus control the risk for developing vascular thrombosis in individuals.

  16. Increased carboxyhemoglobin level during liver resection with inflow occlusion.

    PubMed

    Godai, Kohei; Hasegawa-Moriyama, Maiko; Kuniyoshi, Tamotsu; Matsunaga, Akira; Kanmura, Yuichi

    2013-04-01

    Controlling stress responses associated with ischemic changes due to bleeding and ischemia/reperfusion injury is essential for anesthetic management. Endogenous carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme proteins by the stress-response enzyme heme oxygenase. Although the COHb level is elevated in critically ill patients, changes in endogenous COHb during anesthesia have not been well investigated. Therefore, we evaluated changes in endogenous COHb levels in patients undergoing liver resections with inflow occlusion. Levels of COHb were significantly increased after the Pringle maneuver. The inflow occlusion time in patients with increased COHb after the Pringle maneuver (∆COHb > 0.3 %) was significantly longer than in patients without increased COHb (∆COHb < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion volume of packed red blood cells, operation time, nor anesthetic time differed between patients with and without increased COHb. The results indicated that endogenous COHb levels were increased by inflow occlusion in patients undergoing liver resections, which suggests that changes in COHb may correlate with hepatic ischemia/reperfusion injury induced by inflow occlusion.

  17. Local Burn Injury Promotes Defects in the Epidermal Lipid and Antimicrobial Peptide Barriers in Human Autograft Skin and Burn Margin: Implications for Burn Wound Healing and Graft Survival

    PubMed Central

    Plichta, Jennifer K.; Holmes, Casey J.; Gamelli, Richard L.; Radek, Katherine A.

    2016-01-01

    Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, in order to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In the present study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of pro-inflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury. PMID:27183442

  18. Complete occlusion after blunt injury to the abdominal aorta.

    PubMed

    Meghoo, Colin A L; Gonzalez, Ernest A; Tyroch, Alan H; Wohltmann, Christopher D

    2003-10-01

    Injury to the abdominal aorta after blunt trauma is uncommon. When this injury results in complete vessel occlusion, the presentation is dramatic. Timely intervention is essential. After a case report, we examined all reported cases of complete occlusion after blunt injury to the abdominal aorta and reviewed the cause, presentation, and management of this injury. Complete vessel occlusion arises from intimal injury. The most frequent mechanism is compression from a seat belt or steering wheel during a motor vehicle crash. Patients present with absent femoral and distal pulses in association with lower extremity neuropathy. Intervention commonly involves bypass grafting of the abdominal aorta. Complete occlusion after blunt trauma to the abdominal aorta is rare. Neurologic deficits most commonly arise from peripheral nerve ischemia. Reperfusion within 6 hours confers a greater chance of limb salvage and neurologic recovery.

  19. Aphid watery saliva counteracts sieve-tube occlusion: a universal phenomenon?

    PubMed

    Will, Torsten; Kornemann, Sarah R; Furch, Alexandra C U; Tjallingii, W Fred; van Bel, Aart J E

    2009-10-01

    Ca2+-binding proteins in the watery saliva of Megoura viciae counteract Ca2+-dependent occlusion of sieve plates in Vicia faba and so prevent the shut-down of food supply in response to stylet penetration. The question arises whether this interaction between aphid saliva and sieve-element proteins is a universal phenomenon as inferred by the coincidence between sieve-tube occlusion and salivation. For this purpose, leaf tips were burnt in a number of plant species from four different families to induce remote sieve-plate occlusion. Resultant sieve-plate occlusion in these plant species was counteracted by an abrupt switch of aphid behaviour. Each of the seven aphid species tested interrupted its feeding behaviour and started secreting watery saliva. The protein composition of watery saliva appeared strikingly different between aphid species with less than 50% overlap. Secretion of watery saliva seems to be a universal means to suppress sieve-plate occlusion, although the protein composition of watery saliva seems to diverge between species.

  20. Clinical Experience and Best Practices Using Epidermal Skin Grafts on Wounds.

    PubMed

    Kirsner, Robert S; Bernstein, Brent; Bhatia, Animesh; Lantis, John; Le, Lam; Lincoln, Katherine; Liu, Paul; Rodgers, Lee; Shaw, Mark; Young, David

    2015-11-01

    Over the years, autologous skin grafting has been used extensively to achieve wound closure, optimize a functional scar, and improve aesthetic outcomes for the patient. Although a vast majority of the literature is on the use of full-thickness and split-thickness skin grafts, epidermal skin grafts (ESGs) have emerged as a viable option in the reconstructive ladder when only the epidermal layer is needed. These grafts are distinct from other types of autologous skin grafts in that they can be harvested without anesthesia and leave minimal or no scarring at the donor site. In order to explore the use of ESGs in the continuum of primary wound closure, a multidisciplinary expert panel convened in October 2014, in Las Vegas, NV, to review the scientific basis and clinical uses of epidermal grafting. This publication provides an overview of epidermal grafting, recommendations for graft application, and potential roles for its use in wound care and closure.

  1. [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.

  2. Clinical outcomes in middle cerebral artery trunk occlusions versus secondary division occlusions after mechanical thrombectomy: pooled analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials.

    PubMed

    Shi, Zhong-Song; Loh, Yince; Walker, Gary; Duckwiler, Gary R

    2010-05-01

    The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices. We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days. Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.

  3. Epidermal growth in the bottlenose dolphin, Tursiops truncatus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hicks, B.D.; St. Aubin, D.J.; Geraci, J.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 reconciledmore » 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.« less

  4. Shavenbaby Couples Patterning to Epidermal Cell Shape Control

    PubMed Central

    Fernandes, Isabelle; Roch, Fernando; Payre, François

    2006-01-01

    It is well established that developmental programs act during embryogenesis to determine animal morphogenesis. How these developmental cues produce specific cell shape during morphogenesis, however, has remained elusive. We addressed this question by studying the morphological differentiation of the Drosophila epidermis, governed by a well-known circuit of regulators leading to a stereotyped pattern of smooth cells and cells forming actin-rich extensions (trichomes). It was shown that the transcription factor Shavenbaby plays a pivotal role in the formation of trichomes and underlies all examined cases of the evolutionary diversification of their pattern. To gain insight into the mechanisms of morphological differentiation, we sought to identify shavenbaby's downstream targets. We show here that Shavenbaby controls epidermal cell shape, through the transcriptional activation of different classes of cellular effectors, directly contributing to the organization of actin filaments, regulation of the extracellular matrix, and modification of the cuticle. Individual inactivation of shavenbaby's targets produces distinct trichome defects and only their simultaneous inactivation prevent trichome formation. Our data show that shavenbaby governs an evolutionarily conserved developmental module consisting of a set of genes collectively responsible for trichome formation, shedding new light on molecular mechanisms acting during morphogenesis and the way they can influence evolution of animal forms. PMID:16933974

  5. Impact of the Occlusion Duration on the Performance of J-CTO Score in Predicting Failure of Percutaneous Coronary Intervention for Chronic Total Occlusion.

    PubMed

    de Castro-Filho, Antonio; Lamas, Edgar Stroppa; Meneguz-Moreno, Rafael A; Staico, Rodolfo; Siqueira, Dimytri; Costa, Ricardo A; Braga, Sergio N; Costa, J Ribamar; Chamié, Daniel; Abizaid, Alexandre

    2017-06-01

    The present study examined the association between Multicenter CTO Registry in Japan (J-CTO) score in predicting failure of percutaneous coronary intervention (PCI) correlating with the estimated duration of chronic total occlusion (CTO). The J-CTO score does not incorporate estimated duration of the occlusion. This was an observational retrospective study that involved all consecutive procedures performed at a single tertiary-care cardiology center between January 2009 and December 2014. A total of 174 patients, median age 59.5 years (interquartile range [IQR], 53-65 years), undergoing CTO-PCI were included. The median estimated occlusion duration was 7.5 months (IQR, 4.0-12.0 months). The lesions were classified as easy (score = 0), intermediate (score = 1), difficult (score = 2), and very difficult (score ≥3) in 51.1%, 33.9%, 9.2%, and 5.7% of the patients, respectively. Failure rate significantly increased with higher J-CTO score (7.9%, 20.3%, 50.0%, and 70.0% in groups with J-CTO scores of 0, 1, 2, and ≥3, respectively; P<.001). There was no significant difference in success rate according to estimated duration of occlusion (P=.63). Indeed, J-CTO score predicted failure of CTO-PCI independently of the estimated occlusion duration (P=.24). Areas under receiver-operating characteristic curves were computed and it was observed that for each occlusion time period, the discriminatory capacity of the J-CTO score in predicting CTO-PCI failure was good, with a C-statistic >0.70. The estimated duration of occlusion had no influence on the J-CTO score performance in predicting failure of PCI in CTO lesions. The probability of failure was mainly determined by grade of lesion complexity.

  6. ERK2-mediated C-terminal serine phosphorylation of p300 is vital to the regulation of epidermal growth factor-induced keratin 16 gene expression.

    PubMed

    Chen, Yun-Ju; Wang, Ying-Nai; Chang, Wen-Chang

    2007-09-14

    We previously reported that the epidermal growth factor (EGF) regulates the gene expression of keratin 16 by activating the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling which in turn enhances the recruitment of p300 to the keratin 16 promoter. The recruited p300 functionally cooperates with Sp1 and c-Jun to regulate the gene expression of keratin 16. This study investigated in detail the molecular events incurred upon p300 whereby EGF caused an enhanced interaction between p300 and Sp1. EGF apparently induced time- and dose-dependent phosphorylation of p300, both in vitro and in vivo, through the activation of ERK2. The six potential ERK2 phosphorylation sites, including three threonine and three serine residues as revealed by sequential analysis, were first identified in vitro. Confirmation of these six sites in vivo indicated that these three serine residues (Ser-2279, Ser-2315, and Ser-2366) on the C terminus of p300 were the major signaling targets of EGF. Furthermore, the C-terminal serine phosphorylation of p300 stimulated its histone acetyltransferase activity and enhanced its interaction with Sp1. These serine phosphorylation sites on p300 controlled the p300 recruitment to the keratin 16 promoter. When all three serine residues on p300 were replaced by alanine, EGF could no longer induce the gene expression of keratin 16. Taken together, these results strongly suggested that the ERK2-mediated C-terminal serine phosphorylation of p300 was a key event in the regulation of EGF-induced keratin 16 expression. These results also constituted the first report identifying the unique p300 phosphorylation sites induced by ERK2 in vivo.

  7. The Use of Skeletal Muscle Near Infrared Spectroscopy and a Vascular Occlusion Test at High Altitude

    PubMed Central

    Levett, Denny Z.H.; Bezemer, Rick; Montgomery, Hugh E.; Grocott, Mike P.W.

    2013-01-01

    Abstract Martin, Daniel, Denny Levett, Rick Bezemer, Hugh Montgomery, and Mike Grocott. The use of skeletal muscle near infrared spectroscopy and a vascular occlusion test at high altitude. High Alt Med Biol 14:256–262, 2013.—Microcirculatory function, central to tissue regulation of oxygen flux, may be altered by the chronic hypoxemia experienced at high altitude. We hypothesized that at high altitude, adaptations within skeletal muscle would result in reduced oxygen consumption and reduced microcirculatory responsiveness, detectable by near infrared spectroscopy (NIRS) during a vascular occlusion test (VOT). The VOT comprised 3 min of noninvasive arterial occlusion; thenar eminence tissue oxygenation (Sto2) was measured by NIRS during the VOT at sea level, 4900 m and 5600 m (after 7 and 17 days at altitude, respectively) in 12 healthy volunteers. Data were derived from Sto2 time-curves using specifically designed computer software. Mean (±SD) resting Sto2 was reduced at 4900 m and 5600 m (69.3 (±8.2)% (p=0.001) and 64.2 (±6.1)% (p<0.001) respectively) when compared to sea level (84.4 (±6.0)%. The rate of Sto2 recovery after vascular occlusion (Sto2 upslope) was significantly reduced at 4900 m (2.4 (±0.4)%/sec) and 5600 m (2.4 (±0.8)%/sec) compared to sea level (3.7 (±1.3)%/sec) (p=0.021 and p=0.032, respectively). There was no change from sea level in the rate of desaturation during occlusion (Sto2 downslope) at either altitude. The findings suggest that in resting skeletal muscle of acclimatizing healthy volunteers at high altitude, microvascular reactivity is reduced (Sto2 upslope after a short period of ischemia) but that oxygen consumption remains unchanged (Sto2 downslope). PMID:24067186

  8. Malignant Change in an Epidermal Cyst Over Gluteal Region

    PubMed Central

    Kshirsagar, Ashok Y; Sulhyan, Sanjitsingh R; Deshpande, Shradha; Jagtap, SV

    2011-01-01

    A 72-year-old male presented with a large ulceroproliferative lesion over left gluteal region. After histopathological confirmation of squamous cell carcinoma, the lesion was excised with wide margins. Further histopathological study of the excised specimen revealed the growth arising from an epidermal cyst. Malignant change is a rare, but wellknown complication occurring in an epidermal cyst. The mainstay of treatment consists of wide excision of cancerous lesion with primary reconstruction of the defect. PMID:21572684

  9. Computer modeling of occlusal surfaces of posterior teeth with the CICERO CAD/CAM system.

    PubMed

    Olthoff, L W; Van Der Zel, J M; De Ruiter, W J; Vlaar, S T; Bosman, F

    2000-08-01

    Static and dynamic occlusal interference frequently needs to be corrected by selective grinding of the occlusal surface of conventional cast and ceramic-fused-to-metal restorations. CAD/CAM techniques allow control of the dimensional contours of these restorations. However, parameters responsible for the occlusal form need to be determined. In most articulators, these parameters are set as default values. Which technique is best for minimizing the introduction of occlusal interference in restorations has not been determined. This study investigated differences in crown structure of a crown designed in static occlusion (STA) with designs adapted for dynamic occlusal interferences. Therefore, values from an optoelectronic registration system (String-Condylocomp, KAVO), an occlusal generated path (OGP) technique and default settings (DEF) were used in the CICERO CAD/CAM system. Morphology of CON, DEF, and OGP crowns was compared with that of the STA crown with respect to differences in a buccolingual section and frequency of occlusal distances in an interocclusal range of 1 mm, measured from the occlusal surface of the crown. All crown types fulfilled the esthetic and morphologic criteria for restorations in clinical dentistry. Difference in the morphology of the OGP crown, compared with that of the STA crown, was greater than that for the CON and DEF crowns. These differences were seen especially in the distobuccal part of the occlusal surface; however, the number of occlusal contacts was considered sufficient to stabilize occlusion. Functional occlusion, adapted to dynamic occlusion in a CICERO crown for the first mandibular molar, can be obtained using data acquired with the String-Condylocomp registration system. The OGP technique was preferred to other techniques because of the simplicity of the technique for eliminating potential problems with opposing teeth during motion. However, this is achieved at the cost of fewer points of contact during occlusion than

  10. Intrarenal hemodynamic changes following acute partial renal arterial occlusion.

    DOT National Transportation Integrated Search

    1965-10-01

    Both an increase and a decrease in total renal vascular resistance, following a period of total renal artery occlusion, have been reported from this laboratory. The duration of the occlusive period and height of the perfusion pressure were found to p...

  11. Pulmonary veno-occlusive disease

    MedlinePlus

    ... disorder. Alternative Names Pulmonary vaso-occlusive disease Images Respiratory system References Chin K, Channick RN. Pulmonary hypertension. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  12. Continuous full-time occlusion of the sound eye vs full-time occlusion of the sound eye periodically alternating with occlusion of the amblyopic eye in treatment of amblyopia: a prospective randomized study.

    PubMed

    Stanković, B; Milenković, S

    2007-01-01

    To compare continuous full-time (24 hours per day) occlusion of the sound eye with full-time occlusion (24 hours per day) of the sound eye 1 day more than the years of age periodically alternating with occlusion of the amblyopic eye for 1 day, as treatments for profound strabismic amblyopia in children older than 5 years. A total of 53 patients with visual acuity (VA) of 0.4 and less in the amblyopic eye (tested by crowded Landolt Cs) after previously being provided optimal optical correction were randomly assigned to receive either of the two patching regimens. VA and pattern reversal visual evoked potentials (PVEP) were recorded prospectively at 1-month intervals. Improvement in VA and the reduction in crowding difficulties (CD) were the main outcome measures of the treatment efficiency. Both treatment modalities were equally effective. Of the 51 subjects who completed the study, 21 (41.2%) were cured whereas 32 (62.7%) attained satisfactory improvement. Recovery of VA was related to age, with cure being obtained in 23.5% (4/17) and satisfactory improvement in 52.9% (9/17) of patients older than 9 years. Larger gain in VA influenced the stability of the vision over time. It can be concluded that in clinically monitored parameters both treatment modalities were equally effective without any statistical or clinical significance in the observed groups of patients. However, events like the "trade-off" effect, occurrence of occlusion amblyopia, or prolongation of PVEP latency of the sound eye indicate that full-time continuous occlusion possibly presents a more effective form of treatment.

  13. Gloss, colour and grip: multifunctional epidermal cell shapes in bee- and bird-pollinated flowers.

    PubMed

    Papiorek, Sarah; Junker, Robert R; Lunau, Klaus

    2014-01-01

    Flowers bear the function of filters supporting the attraction of pollinators as well as the deterrence of floral antagonists. The effect of epidermal cell shape on the visual display and tactile properties of flowers has been evaluated only recently. In this study we quantitatively measured epidermal cell shape, gloss and spectral reflectance of flowers pollinated by either bees or birds testing three hypotheses: The first two hypotheses imply that bee-pollinated flowers might benefit from rough surfaces on visually-active parts produced by conical epidermal cells, as they may enhance the colour signal of flowers as well as the grip on flowers for bees. In contrast, bird-pollinated flowers might benefit from flat surfaces produced by flat epidermal cells, by avoiding frequent visitation from non-pollinating bees due to a reduced colour signal, as birds do not rely on specific colour parameters while foraging. Moreover, flat petal surfaces in bird-pollinated flowers may hamper grip for bees that do not touch anthers and stigmas while consuming nectar and thus, are considered as nectar thieves. Beside this, the third hypothesis implies that those flower parts which are vulnerable to nectar robbing of bee- as well as bird-pollinated flowers benefit from flat epidermal cells, hampering grip for nectar robbing bees. Our comparative data show in fact that conical epidermal cells are restricted to visually-active parts of bee-pollinated flowers, whereas robbing-sensitive parts of bee-pollinated as well as the entire floral surface of bird-pollinated flowers possess on average flat epidermal cells. However, direct correlations between epidermal cell shape and colour parameters have not been found. Our results together with published experimental studies show that epidermal cell shape as a largely neglected flower trait might act as an important feature in pollinator attraction and avoidance of antagonists, and thus may contribute to the partitioning of flower-visitors.

  14. Evaluation of the Alteration of Occlusal Distribution in Unilateral Free-End and Intermediate Missing Cases.

    PubMed

    Kon, Kazuhiro; Shiota, Makoto; Sakuyama, Aoi; Ozeki, Maho; Kozuma, Wataru; Kawakami, Sawako; Kasugai, Shohei

    2017-02-01

    The present study aimed to evaluate the effect of implant prostheses on the occlusal force and area as well as the distribution of occlusal loading in unilateral free-end and intermediate missing cases. Fourteen healthy subjects (7 free-end missing cases in the first and second molars and 7 intermediate missing cases in the first molar region) were included. Six months after the implant prosthesis was placed, an occlusal evaluation was performed with or without the implant superstructure by using Dental Prescale film and an occluder device. In free-end missing cases, the total occlusal force and area, implant-side occlusal force and area, and implant-side occlusal force and area of the residual natural teeth were significantly affected by the implant prostheses. In intermediate missing cases, the implant-side occlusal force of the residual natural teeth was significantly affected by the implant prostheses. In free-end missing cases, the proportions of implant-side occlusal force, non-implant-side occlusal force, and implant-side occlusal force of the residual natural teeth relative to the total occlusal force were significantly affected by the implant prostheses. In the intermediate missing cases, the proportion of the implant-side occlusal force of the residual natural teeth relative to the total occlusal force was significantly affected by the implant prostheses. The proportion of the occlusal area was also significantly affected. In free-end missing cases, implant prostheses significantly increased the occlusal force and area, which resulted in the proper occlusal distribution. In intermediate missing cases, an implant prosthesis may only improve the same-side occlusal loading of the natural teeth.

  15. Influence of Articulating Paper Thickness on Occlusal Contacts Registration: A Preliminary Report.

    PubMed

    Brizuela-Velasco, Aritza; Álvarez-Arenal, Ángel; Ellakuria-Echevarria, Joseba; del Río-Highsmith, Jaime; Santamaría-Arrieta, Gorka; Martín-Blanco, Nerea

    2015-01-01

    The objective of this preliminary study was to determine if the occlusal contact surface registered with an articulating paper during fixed prosthodontic treatment was contained within the area marked on a thicker articulating paper. This information would optimize any necessary occlusal adjustment of a prosthesis' veneering material. A convenience sample of 15 patients who were being treated with an implant-supported fixed singleunit dental prosthesis was selected. Occlusal registrations were obtained from each patient using 12-μm, 40-μm, 80-μm, and 200-μm articulating paper. Photographs of the occlusal registrations were obtained, and pixel measurements of the surfaces were taken and overlapped for comparison. The results showed that the thicker the articulating paper, the larger the occlusal contact area obtained. The differences were statistically significant. In all cases, the occlusal registrations obtained with the thinnest articulating paper were contained within the area marked on the thickest articulating paper. The results suggested that the use of thin articulating papers (12-μm or 40-μm) can avoid unnecessary grinding of veneering material or teeth during occlusal adjustment.

  16. 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

  17. ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

  18. Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

    PubMed

    Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

    2016-02-01

    Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor

  19. Pressure monitoring predicts pulmonary vein occlusion in cryoballoon ablation.

    PubMed

    Sunaga, Akihiro; Masuda, Masaharu; Asai, Mitsutoshi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Matsuda, Yasuhiro; Okuno, Syota; Mano, Toshiaki

    2018-04-10

    Pulmonary venography is routinely used to confirm pulmonary vein (PV) occlusion during cryoballoon ablation. However, this technique is significantly limited by the risks associated with contrast media, such as renal injury and contrast allergy. We hypothesized that PV occlusion can be predicted by elevation of the balloon catheter tip pressure, avoiding the need for contrast media. Forty-eight consecutive patients with paroxysmal atrial fibrillation who underwent PV isolation with the cryoballoon technique were enrolled. The balloon catheter tip pressure was measured in each PV before and after balloon inflation. We analyzed 200 applications of cryoballoon ablation in 185 PVs (excluding 3 common PVs and 1 extremely small right inferior PV) of 48 patients (age, 70 ± 11 years; male, n = 28; mean left atrial diameter, 38 ± 6 mm). Compared with patients with unsuccessful occlusion, patients with successful occlusion demonstrated a larger change in pressure after balloon inflation (6 ± 8 vs. 2 ± 4 mmHg, P < 0.001), a lower minimum temperature (- 49 ± 6 vs. - 40 ± 8 °C, P < 0.001), and a higher PV isolation rate (97 vs. 64%, P < 0.001). The best cutoff value of a change in pressure for predicting PV occlusion was 4.5 mmHg, with a sensitivity of 67%, specificity of 83%, and predictive accuracy of 72%. Pressure monitoring is helpful to confirm PV occlusion during cryoballoon ablation.

  20. Occlusal factors are not related to self-reported bruxism.

    PubMed

    Manfredini, Daniele; Visscher, Corine M; Guarda-Nardini, Luca; Lobbezoo, Frank

    2012-01-01

    To estimate the contribution of various occlusal features of the natural dentition that may identify self-reported bruxers compared to nonbruxers. Two age- and sex-matched groups of self-reported bruxers (n = 67) and self-reported nonbruxers (n = 75) took part in the study. For each patient, the following occlusal features were clinically assessed: retruded contact position (RCP) to intercuspal contact position (ICP) slide length (< 2 mm was considered normal), vertical overlap (< 0 mm was considered an anterior open bite; > 4 mm, a deep bite), horizontal overlap (> 4 mm was considered a large horizontal overlap), incisor dental midline discrepancy (< 2 mm was considered normal), and the presence of a unilateral posterior crossbite, mediotrusive interferences, and laterotrusive interferences. A multiple logistic regression model was used to identify the significant associations between the assessed occlusal features (independent variables) and self-reported bruxism (dependent variable). Accuracy values to predict self-reported bruxism were unacceptable for all occlusal variables. The only variable remaining in the final regression model was laterotrusive interferences (P = .030). The percentage of explained variance for bruxism by the final multiple regression model was 4.6%. This model including only one occlusal factor showed low positive (58.1%) and negative predictive values (59.7%), thus showing a poor accuracy to predict the presence of self-reported bruxism (59.2%). This investigation suggested that the contribution of occlusion to the differentiation between bruxers and nonbruxers is negligible. This finding supports theories that advocate a much diminished role for peripheral anatomical-structural factors in the pathogenesis of bruxism.

  1. Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma.

    PubMed

    Caviedes-Bucheli, J; Gomez-Sosa, J F; Azuero-Holguin, M M; Ormeño-Gomez, M; Pinto-Pascual, V; Munoz, H R

    2017-04-01

    Angiogenesis is the formation of new blood vessels based on a pre-existing vasculature. It comprises two processes, sprouting of endothelial cells and the division of vessels due to abnormal growth of the microvasculature. It has been demonstrated that substance P (SP) can induce angiogenesis either by modulating endothelial cell growth (direct mechanism) or by attracting cells with angiogenic potential to the injury site (indirect mechanism). Therefore, the purpose of this article is to review the angiogenic mechanisms that regulate mineralized tissue formation in human dental pulp tissue and their relationship with SP expression as a defence response to stimuli such as the masticatory function and occlusal trauma. Articles included in this review were searched in PubMed, Scopus and ISI Web of Science databases, combining the following keywords: human dentine pulp, angiogenesis, angiogenic growth factors, neuropeptides, substance P, neurogenic inflammation, dentine matrix, dentinogenesis, occlusal trauma and dental occlusion. It is concluded that human dental pulp tissue responds to occlusal trauma and masticatory function with a neurogenic inflammatory phenomenon in which SP plays an important role in the direct and indirect mechanisms of angiogenesis by the action evoked via NK1 receptors at different cells, such as fibroblasts, endothelial and inflammatory cells, leading to new blood vessel formation which are needed to stimulate mineralized tissue formation as a defence mechanism. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  2. Halobetasol Propionate Lotion, 0.05% Provides Superior Hydration Compared to Halobetasol Propionate Cream, 0.05% in a Double-Blinded Study of Occlusivity and Hydration.

    PubMed

    Grove, Gary; Zerweck, Charles; Houser, Tim; Andrasfay, Anthony; Gauthier, Bob; Holland, Charles; Piacquadio, Daniel

    2017-02-01

    This study measured skin hydration and occlusivity of two test products [halobetasol propionate lotion, 0.05% (HBP Lotion) and Ultravate® (halobetasol propionate) cream, 0.05% (HBP Cream)] at 2, 4, and 6 hours after application to skin test sites previously challenged by dry shaving, which was performed to compromise the integrity of the stratum corneum barrier. Trans-epidermal water loss (TEWL), an indicator of skin barrier function, was measured using cyberDERM, inc. RG-1 evaporimeter. Skin hydration was evaluated using IBS SkiCon-200 conductance meter. Test products were applied bilaterally on dry-shaved sites on the volar forearm sites, according to a randomization scheme, with two test sites untreated to serve as "dry-shaved" controls. TEWL and conductance were measured at 2, 4, and 6 hours post-treatment. HBP Lotion displayed a significant increase in skin hydration at 2, 4, and 6 hours post-treatment compared to the baseline values and dry-shaved controls (each, P less than 0.001). However, HBP Cream produced statistically significant increased skin hydration only after 6 hours (P less than 0.05). HBP Lotion was significantly more effective than HBP Cream in increasing skin hydration at 2 and 4 hours post-treatment (each, P less than 0.001), and had a directional advantage (not statistically significant) at 6 hours. Neither test product had a significant occlusive effect as measured by TEWL at 2, 4, and 6 hours post-application. Both formulations of HBP (Lotion and Cream) contributed to skin moisturization, as measured by skin conductance. HBP Lotion produced a significantly more rapid onset and higher level of moisturization at 2 and 4 hours post-application compared to HBP Cream. The TEWL results indicate that neither HBP Lotion nor HBP Cream provided any significant occlusivity to the skin.

    J Drugs Dermatol. 2017;16(2):140-144.

    .

  3. Amplatzer vascular plug for rapid vessel occlusion in interventional neuroradiology

    PubMed Central

    Banfield, Jillian C

    2016-01-01

    The purpose of this paper is to report different uses of endovascular Amplatzer vascular plug (AVP) treatment for rapid vessel occlusion in the field of interventional neuroradiology. We retrospectively reviewed our interventional neuroradiology database from November 2010 to July 2015 and found nine patients who were treated with endovascular AVP. AVP was used for rapid vessel occlusion of common carotid artery (1 patient), internal carotid artery (5 patients), vertebral artery (2 patients), and internal jugular vein (1 patient). A median of three AVPs were used with almost immediate occlusion and no thromboembolic complications. Use of AVP is feasible, safe, rapid, and potentially cost-effective method for rapid occlusion of larger size vessels in the head and neck region for different indications. PMID:26515699

  4. History of materials used for recording static and dynamic occlusal contact marks: a literature review

    PubMed Central

    Rahul, G R.; Poduval, Soorya T.; Shetty, Karunakar; Gupta, Bhawna; Rajora, Varun

    2013-01-01

    In the discipline of prosthetic dentistry it is important not only to examine the occlusion, but to be able to record, store, and transfer the information. Over the years many occlusion testing materials have been used. It has been suggested the clinical recording and transfer of information using waxes and other occlusion recording materials have disadvantages relating to inaccuracy and problems of manipulation. Therefore, there has been introduction of many new systems for recording occlusion contacts to overcome such problems. The correct physiological recovery of occlusion posses as much a challenge as ever for every dentist and technician. Even the smallest high spots measuring just a few microns can cause dysfunctions like temporo-mandibular pain. Occlusal proportions are being constantly changed with every procedure. Therefore, an understanding of the synergy of the teeth in static and dynamic occlusion forms the basis of good dentistry. The purpose of this review article is to give and overview of the various materials and methods that have been used to record occlusal contact marks. Key words:Occlusal contact marks, Occlusion indicators, Occlusion test materials, Occlusion recording materials. PMID:24455051

  5. Rhythmic autocrine activity in cultured insect epidermal cells.

    PubMed

    Mesnier, M; Partiaoglou, N; Oberlander, H; Porcheron, P

    2000-05-01

    It is now well established that ecdysteroids can be produced in insects in the absence of prothoracic glands. In this respect, it has been shown that cells in culture can produce ecdysteroids. Our aims were: (1) to determine whether ecdysteroid target cells of epidermal origin could also be the source of ecdysteroids; (2) to monitor more accurately the kinetics of ecdysteroid production; and (3) to check for possible relationships between this synthetic activity and dynamics of cell division. An insect cell line (IAL-PID2) established from imaginal discs of the Indian meal moth, Plodia interpunctella, with wild-type sensitivity to ecdysteroids was used in our study. Our results showed that the Plodia cell line exhibited autocrine activity. When division of IAL-PID2 cells was synchronized, a rhythmic production of ecdysteroids was observed. However, further experiments indicated that this rhythmicity could be cell autonomous. This led us to anticipate the existence of two cell subpopulations that would be able to produce ecdysteroids rhythmically, a minor one that would be cell cycle serum-independent population, and a major population that would need serum growth factors to proliferate and produce ecdysteroids. Qualitative study of the ecdysteroid content of the media clearly showed that ecdysone was the major immunoreactive product. Taken together, our findings clearly show that an insect cell line of epidermal origin is capable of rhythmic autocrine production of ecdysteroids. These results support the hypothesis that alternate sites for ecdysteroid production in vivo may exist and could play a role in local regulation of development. We now plan to determine the cellular basis of this rhythmic autocrine activity and to confirm the existence of growth factor-autonomous cells in the culture as well as the potent role played by ecdysteroids in the cross-talk between various cell subpopulations. Copyright 2000 Wiley-Liss, Inc.

  6. Microfluidics for investigating vaso-occlusions in sickle cell disease.

    PubMed

    Horton, Renita E

    2017-07-01

    SCD stems from amutation in the beta globin gene. Upon deoxygenation, hemoglobin polymerizes and triggers RBC remodeling. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications; unfortunately, the complex mechanisms that contribute to vaso-occlusions are not well understood. Vaso-occlusions can occur in post-capillary venules; hence, the microvasculature is a prime target for SCD therapies. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivo systems. However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and ECM presentation. This review, although not comprehensive, highlights microfluidic approaches that aim to improve our current understanding of the pathophysiological mechanisms surrounding SCD. Microfluidic platforms can aid in identifying factors that may contribute to disease severity and can serve as suitable test beds for novel treatment strategies which may improve patient outcomes. © 2017 John Wiley & Sons Ltd.

  7. Influence of occlusal loading on peri-implant clinical parameters. A pilot study

    PubMed Central

    Pellicer-Chover, Hilario; Viña-Almunia, José; Romero-Millán, Javier; Peñarrocha-Oltra, David; Peñarrocha-Diago, María

    2014-01-01

    Objectives: To investigate the relation between occlusal loading and peri-implant clinical parameters (probing depth, bleeding on probing, gingival retraction, width of keratinized mucosa, and crevicular fluid volume) in patients with implant-supported complete fixed prostheses in both arches. Material and Methods: This clinical study took place at the University of Valencia (Spain) dental clinic. It included patients attending the clinic for regular check-ups during at least 12 months after rehabilitation of both arches with implant-supported complete fixed ceramo-metallic prostheses. One study implant and one control implant were established for each patient using the T-Scan®III computerized system (Tesco, South Boston, USA). The maxillary implant closest to the point of maximum occlusal loading was taken as the study implant and the farthest (with least loading) as the control. Occlusal forces were registered with the T-Scan® III and then occlusal adjustment was performed to distribute occlusal forces correctly. Peri-implant clinical parameters were analyzed in both implants before and two and twelve months after occlusal adjustment. Results: Before occlusal adjustment, study group implants presented a higher mean volume of crevicular fluid (51.3±7.4 UP) than the control group (25.8±5.5 UP), with statistically significant difference. Two months after occlusal adjustment, there were no significant differences between groups (24.6±3.8 UP and 26±4.5 UP respectively) (p=0.977). After twelve months, no significant differences were found between groups (24.4±11.1 UP and 22.5±8.9 UP respectively) (p=0.323). For the other clinical parameters, no significant differences were identified between study and control implants at any of the study times (p>0.05). Conclusions: Study group implants receiving higher occlusal loading presented significantly higher volumes of crevicular fluid than control implants. Crevicular fluid volumes were similar in both groups two and

  8. Down-regulation of microRNA-146a is associated with high-risk human papillomavirus infection and epidermal growth factor receptor overexpression in penile squamous cell carcinoma.

    PubMed

    Peta, Elektra; Cappellesso, Rocco; Masi, Giulia; Sinigaglia, Alessandro; Trevisan, Marta; Grassi, Angela; Di Camillo, Barbara; Vassarotto, Elisa; Fassina, Ambrogio; Palù, Giorgio; Barzon, Luisa

    2017-03-01

    Dysregulation of host microRNA expression has been involved in the development and progression of human papillomavirus (HPV)-related tumors. Analysis of miR-146a expression in a series of 59 penile squamous cell carcinomas (PSCCs) showed that its levels were lower in high-risk HPV-positive than in HPV-negative PSCCs and inversely correlated with expression of epidermal growth factor receptor (EGFR), a known target for miR-146a. Analysis of genotype distribution for rs2910164, a common functional polymorphism of miR-146a, did not identify correlations with miR-146a levels and EGFR expression in PSCCs. In vitro experiments demonstrated that E6 of HPV type 16, but not low-risk HPV-6, down-regulated miR-146a in human foreskin keratinocytes and up-regulated EGFR. Ectopic expression of miR-146a decreased expression of EGFR and inhibited proliferation of keratinocytes and cervical carcinoma cells. EGFR is commonly overexpressed in penile cancer and in other squamous cell carcinomas. Molecular mechanisms leading to EGFR overexpression and activation are known for HPV-negative cancers and include amplification or mutations of the EGFR gene. The results of this study indicate that down-regulation of miR-146a may represent another mechanism of EGFR overexpression in PSCCs, which can be mediated by high-risk HPV E6 in HPV-related tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. [Enhanced lymphocyte proliferation in the presence of epidermal cells of HIV-infected patients in vitro].

    PubMed

    Kappus, R P; Berger, S; Thomas, C A; Ottmann, O G; Ganser, A; Stille, W; Shah, P M

    1992-07-01

    Clinical observations show that the HIV infection is often associated with affections of the skin. In order to examine the involvement of the epidermal immune system in the HIV infection, we determined accessory cell function of epidermal cells from HIV-1-infected patients. For this we measured the proliferative response of enriched CD(4+)-T-lymphocytes from HIV-infected patients and noninfected controls to stimulation with anti-CD3 and IL-2 in the presence of epidermal cells; the enhancement of the response is dependent on the presence of functionally intact accessory cells. The capacity of epidermal cells to increase the anti-CD3-stimulated T-cell proliferative response was significantly enhanced in HIV patients (CDC III/IVA) as compared with noninfected donors. It is discussed, whether the increased activity of epidermal cells from HIV-infected patients may be responsible for several of the dermal lesions in the course of an HIV infection as due to an enhanced production and release of epidermal cell-derived cytokines.

  10. Time Sequence Evaluation of Biliary Stent Occlusion by Dissection Analysis of Retrieved Stents.

    PubMed

    Kwon, Chang-Il; Gromski, Mark A; Sherman, Stuart; Easler, Jeffrey J; El Hajj, Ihab I; Watkins, James; Fogel, Evan L; McHenry, Lee; Lehman, Glen A

    2016-08-01

    Multiple factors can affect the occlusion of plastic stents. Previous data demonstrate that side holes may induce more biofilm formation probably via microturbulence and bile flow disturbances that could lead to occlusion. These results, however, have not been replicated in subsequent clinical studies with different methods. The objective of this study is to evaluate the physical characteristics of plastic stent occlusion over time. This is a plastic stent sequential analysis study. Biliary stents removed via ERCP from February 24, 2015, to June 2, 2015, were included. One hundred and forty-eight retrieved straight-type plastic stents were longitudinally cut by a custom-made cutting device. These dissected stents were then evaluated in detail with regard to the location of stent occlusion and the stent patency period. Location of stent occlusive debris was the primary outcome in this study. Biofilm formations and occlusions by debris were sequentially but separately tallied. Biofilm formations were initially seen around the side hole areas within 30 days and spread to the entire stent by 60 days. Then, occlusion process by debris was mainly initiated by 80 days and progressed to full occlusion by median of 90 days. Although some occlusions were also observed around the side hole areas within 30 days, affected areas were more widely observed after biofilm formation. This study is the first to attempt to describe the distribution of stent occlusions over time. These observations may help guide future stent development.

  11. The muscle engram: the reflex that limits conventional occlusal treatment.

    PubMed

    Lerman, Martin D

    2011-10-01

    The engram (the masticatory "muscle memory") is shown to be a conditionable reflex whose muscle conditioning lasts less than two minutes, far shorter than previously thought. This reflex, reinforced and stored in the masticatory muscles at every swallow, adjusts masticatory muscle activity to guide the lower arch unerringly into its ICP. These muscle adjustments compensate for the continually changing intemal and external factors that affect the mandible's entry into the ICP. A simple quick experiment described in this article isolates the engram, enabling the reader to see its action clearly for the first time. It is urged that every reader perform this experiment. This experiment shows how the engram, by hiding the masticatory muscles' reaction (the hit-and-slide), limits the success of the therapist in achieving occlusion-muscle compatibility. This finding has major clinical implications. It means that, as regards the muscle aspect of treating occlusion, the dentist treating occlusion conventionally is working blind, a situation the neuromuscular school of occlusal thought seeks to correct. The controversy over occlusion continues.

  12. A study of parallelism of the occlusal plane and ala-tragus line.

    PubMed

    Sadr, Katayoun; Sadr, Makan

    2009-01-01

    Orientation of the occlusal plane is one of the most important clinical procedures in prostho-dontic rehabilitation of edentulous patients. The aim of this study was to define the best posterior reference point of ala-tragus line for orientation of occlusal plane for complete denture fabrication. Fifty-three dental students (27 females and 26 males) with complete natural dentition and Angel's Class I occlusal relationship were selected. The subjects were photographed in natural head position while clenching on a Fox plane. After tracing the photographs, the angles between the following lines were measured: the occlusal plane (Fox plane) and the superior border of ala-tragus, the occlusal plane (Fox plane) and the middle of ala-tragus as well as the occlusal plane (Fox plane) and the inferior border of ala-tragus. Descriptive statistics, one sample t-test and independent t-test were used. P value less than 0.05 was considered significant. There was no parallelism between the occlusal plane and ala-tragus line with three different posterior ends and one sample t-test showed that the angles between them were significantly different from zero (p<0.05). However, the supe-rior border of ala-tragus line had the lowest mean angle, 1.80° (3.12) and was almost parallel to the occlusal plane. The superior border of the tragus is suggested as the posterior reference for ala-tragus line.

  13. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    PubMed

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Multiple transcription factor codes activate epidermal wound–response genes in Drosophila

    PubMed Central

    Pearson, Joseph C.; Juarez, Michelle T.; Kim, Myungjin; Drivenes, Øyvind; McGinnis, William

    2009-01-01

    Wounds in Drosophila and mouse embryos induce similar genetic pathways to repair epidermal barriers. However, the transcription factors that transduce wound signals to repair epidermal barriers are largely unknown. We characterize the transcriptional regulatory enhancers of 4 genes—Ddc, ple, msn, and kkv—that are rapidly activated in epidermal cells surrounding wounds in late Drosophila embryos and early larvae. These epidermal wound enhancers all contain evolutionarily conserved sequences matching binding sites for JUN/FOS and GRH transcription factors, but vary widely in trans- and cis-requirements for these inputs and their binding sites. We propose that the combination of GRH and FOS is part of an ancient wound–response pathway still used in vertebrates and invertebrates, but that other mechanisms have evolved that result in similar transcriptional output. A common, but largely untested assumption of bioinformatic analyses of gene regulatory networks is that transcription units activated in the same spatial and temporal patterns will require the same cis-regulatory codes. Our results indicate that this is an overly simplistic view. PMID:19168633

  15. Perforator Flaps after Excision of Large Epidermal Cysts in the Buttocks

    PubMed Central

    Kim, Sang Wha; Yang, Seong Hyeok; Kim, Jeong Tae

    2014-01-01

    Background Epidermal cysts are commonly occurring masses usually less than 5 cm in diameter, but in predisposed patients, epidermal cysts can grow relatively large due to chronic infection. Methods From June 2002 to July 2010, 17 patients received 19 regional perforator-based island flaps to cover defects due to the excision of large epidermal cysts (diameter >5 cm) in the buttocks. Eight patients had diabetes, and seven had rheumatoid arthritis. The pedicles were not fully isolated to prevent spasms or twisting. Results All the flaps survived completely, except for one case with partial necrosis of the flap, which necessitated another perforator-based island flap for coverage. There were two cases of wound dehiscence, which were re-closed after meticulous debridement. There were no recurrences of the masses during follow-up periods of 8.1 months (range, 6-12 months). Conclusions In patients with large epidermal cysts and underlying medical disorders, regional perforator-based island flaps can be the solution to coverage of the defects after excision. PMID:24665422

  16. Novel Evidence-Based Classification of Cavernous Venous Occlusive Disease.

    PubMed

    Pathak, Ram A; Rawal, Bhupendra; Li, Zhuo; Broderick, Gregory A

    2016-10-01

    The primary aim of our study was to determine whether an evidence-based rationale could categorize cavernous venous occlusive disease into mild, moderate and severe erectile dysfunction. A total of 863 patients underwent color duplex Doppler ultrasound from January 2010 to June 2013 performed by a single urologist. We identified a cohort of 75 patients (8.7%) with a diagnosis of cavernous venous occlusive disease based on a unilateral resistive index less than 0.9, and right and left peak systolic velocity 35 cm per second or less after visual sexual stimulation. At a median followup of 13 months patients were evaluated for treatment efficacy. A total of 75 patients with a median age of 60 years (range 19 to 83) and a mean body mass index of 26.3 kg/m(2) (range 19.0 to 39.3) satisfied the criteria of cavernous venous occlusive disease. When substratified into tertiles, resistive index cutoffs were obtained, including mild cavernous venous occlusive disease-81.6 to 94.0, moderate disease-72.6 to 81.5 and severe disease-59.5 to 72.5. Using these 3 groups the phosphodiesterase type 5-inhibitor failure rate (p = 0.017) and SHIM (Sexual Health Inventory for Men) score categories (1 to 10 vs 11 to 20, p = 0.030) were statistically significantly different for mild, moderate and severe cavernous venous occlusive disease. Treatment satisfaction was also statistically significantly different. Penile prosthetic placement was a more common outcome among patients with erectile dysfunction and more severe cavernous venous occlusive disease. Our retrospective analysis supports a correlation between the phosphodiesterase type 5 inhibitor failure rate, SHIM score and the rate of surgical intervention using resistive index values. Our data further suggest that an evidence-based classification of cavernous venous occlusive disease by color Doppler ultrasound is possible and can triage patients to penile prosthetic placement. Copyright © 2016 American Urological Association

  17. Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation.

    PubMed

    Bianchi, E; Ripandelli, G; Feher, J; Plateroti, A M; Plateroti, R; Kovacs, I; Plateroti, P; Taurone, S; Artico, M

    2015-01-01

    The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

  18. Early endovascular treatment of superior mesenteric occlusion secondary to thromboemboli.

    PubMed

    Jia, Z; Jiang, G; Tian, F; Zhao, J; Li, S; Wang, K; Wang, Y; Jiang, L; Wang, W

    2014-02-01

    To evaluate our early experience with endovascular revascularization in patients with acute thromboembolic occlusion of the superior mesenteric artery (SMA). A retrospective review was conducted of all patients who underwent endovascular revascularization for acute thromboembolic SMA occlusion from May 2005 to May 2012. Endovascular revascularization was performed using aspiration, intra-arterial thrombolysis, and adjunctive stent-placement techniques. Laparotomy was performed if the patient developed clinical signs of advanced bowel ischemia after endovascular procedure. Twenty-one patients underwent endovascular revascularization for acute thromboembolic SMA occlusion. All presented with acute-onset abdominal pain. Three patients had rebound tenderness before the procedure. Computed tomography angiography revealed complete occlusion in seven cases and incomplete occlusion in 14 cases, with no evidence of free gas or bowel necrosis. The median duration from onset of symptoms to revascularization was 8.7 ± 4.1 hours (range, 2-18 hours). Completely successful endovascular revascularization occurred in six cases (aspiration alone, 3 cases; combined aspiration and urokinase, 3 cases); partial success was achieved in 15 cases (aspiration alone, 4 cases; combined aspiration and urokinase, 10 cases; and combined aspiration, urokinase, and stent placement, 1 case). Laparotomy was required in five patients, all of whom had SMA main trunk complete occlusion and required small bowel resection. The 30-day mortality for all patients was 9.5%. During a median follow-up of 26 months, 15 patients remained asymptomatic, three patients reported occasional abdominal pain, and one patient had temporary short-bowel syndrome. Percutaneous revascularization is a promising alternative to surgery for acute SMA occlusion in selected patients who have no signs of advanced bowel ischemia. Early diagnosis followed by prompt endovascular intervention with close postprocedural monitoring is

  19. Effect of occlusal vertical dimension on lip positions at smile.

    PubMed

    Chou, Jang-Ching; Thompson, Geoffrey A; Aggarwal, Harshit A; Bosio, Jose A; Irelan, Jon P

    2014-09-01

    In complete mouth reconstructive dentistry, the occlusal vertical dimension may be increased to provide adequate restorative space or to improve esthetics. The effect of increasing the occlusal vertical dimension on the smile is not well understood. The purpose of this study was to evaluate the effect of increasing the occlusal vertical dimension on the dimensions of the smile. Thirty dental students, 12 men and 18 women between the ages of 21 and 30 years old, participated in this study. Polyvinyl siloxane occlusal registrations 2, 4, 6, and 8 mm in thickness were fabricated from articulated stone casts. Posed smile images at occlusal vertical dimension +0, +2, +4, +6, and +8 mm were made with a digital single lens reflex camera mounted on a tripod. A wall-mounted head-positioning device, modified from a cephalometric unit, was used to stabilize the head position. Interlabial gap height, intercommissural width, incisal edge to upper lip, and incisal edge-to-lower lip measurements were made with computer software. The smile index was obtained by dividing width by height. The display zone area was measured by using computer software tracing. One-way repeated measures ANOVA (α=.05) was used for statistical analysis. With an increase in the occlusal vertical dimension, the interlabial gap height, incisal edge to lower lip distance, and display zone area increased significantly (P<.001), whereas the smile index decreased significantly (P<.001). No significant changes were observed in the intercommissural width and incisal edge to upper lip distance. The interlabial gap height, incisal edge-to-lower lip distance, and display zone area increase with increased occlusal vertical dimension. The smile index decreases with increased occlusal vertical dimension. However, the width of the smile and the length of the upper lip tend to remain unchanged. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights

  20. Clinical Decision Support Model to Predict Occlusal Force in Bruxism Patients.

    PubMed

    Thanathornwong, Bhornsawan; Suebnukarn, Siriwan

    2017-10-01

    The aim of this study was to develop a decision support model for the prediction of occlusal force from the size and color of articulating paper markings in bruxism patients. We used the information from the datasets of 30 bruxism patients in which digital measurements of the size and color of articulating paper markings (12-µm Hanel; Coltene/Whaledent GmbH, Langenau, Germany) on canine protected hard stabilization splints were measured in pixels (P) and in red (R), green (G), and blue (B) values using Adobe Photoshop software (Adobe Systems, San Jose, CA, USA). The occlusal force (F) was measured using T-Scan III (Tekscan Inc., South Boston, MA, USA). The multiple regression equation was applied to predict F from the P and RGB. Model evaluation was performed using the datasets from 10 new patients. The patient's occlusal force measured by T-Scan III was used as a 'gold standard' to compare with the occlusal force predicted by the multiple regression model. The results demonstrate that the correlation between the occlusal force and the pixels and RGB of the articulating paper markings was positive (F = 1.62×P + 0.07×R -0.08×G + 0.08×B + 4.74; R 2 = 0.34). There was a high degree of agreement between the occlusal force of the patient measured using T-Scan III and the occlusal force predicted by the model (kappa value = 0.82). The results obtained demonstrate that the multiple regression model can predict the occlusal force using the digital values for the size and color of the articulating paper markings in bruxism patients.

  1. Clinical Decision Support Model to Predict Occlusal Force in Bruxism Patients

    PubMed Central

    Thanathornwong, Bhornsawan

    2017-01-01

    Objectives The aim of this study was to develop a decision support model for the prediction of occlusal force from the size and color of articulating paper markings in bruxism patients. Methods We used the information from the datasets of 30 bruxism patients in which digital measurements of the size and color of articulating paper markings (12-µm Hanel; Coltene/Whaledent GmbH, Langenau, Germany) on canine protected hard stabilization splints were measured in pixels (P) and in red (R), green (G), and blue (B) values using Adobe Photoshop software (Adobe Systems, San Jose, CA, USA). The occlusal force (F) was measured using T-Scan III (Tekscan Inc., South Boston, MA, USA). The multiple regression equation was applied to predict F from the P and RGB. Model evaluation was performed using the datasets from 10 new patients. The patient's occlusal force measured by T-Scan III was used as a ‘gold standard’ to compare with the occlusal force predicted by the multiple regression model. Results The results demonstrate that the correlation between the occlusal force and the pixels and RGB of the articulating paper markings was positive (F = 1.62×P + 0.07×R –0.08×G + 0.08×B + 4.74; R2 = 0.34). There was a high degree of agreement between the occlusal force of the patient measured using T-Scan III and the occlusal force predicted by the model (kappa value = 0.82). Conclusions The results obtained demonstrate that the multiple regression model can predict the occlusal force using the digital values for the size and color of the articulating paper markings in bruxism patients. PMID:29181234

  2. Effectiveness of various toothpastes on dentine tubule occlusion.

    PubMed

    Arnold, W H; Prange, M; Naumova, E A

    2015-04-01

    Dentine hypersensitivity is an increasing problem in dentistry. Several products are available that claim to occlude open dentine tubules and to reduce dentine hypersensitivity. The aim of this study was to investigate the effectiveness of several different products on dentine tubule occlusion using qualitative and quantitative methods. Dentine discs were prepared from extracted human premolars and molars. The dentine discs were brushed with 6 different experimental toothpastes, 1 positive control toothpaste and 1 negative control without toothpaste; the brushing simulated a total brushing time of 1 year. Half of the discs were etched with lemon juice after toothpaste application. Standardized scanning electron microphotographs were taken and converted into binary black and white images. The black pixels, which represented the open dentine tubules, were counted and statistically evaluated. Then, half of the dentine discs were broken, and the occlusion of the dentine tubules was investigated using energy dispersive X-ray spectroscopy (EDS). The number of open dentine tubules decreased significantly after brushing with 5 of the 6 tested toothpastes. A significant effect was observed after acid erosion for 3 of the 6 tested toothpastes. EDS revealed partly closed dentine tubules after brushing with 3 toothpastes; however, no partly closed dentine tubules were observed after acid erosion. Some toothpastes are capable of partial dentine tubule occlusion. This occlusion is unstable and can be removed with acid erosion. Desensitizing toothpastes are the most common products that are used against dentine hypersensitivity, and these toothpastes affect dentine tubule occlusion. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis.

    PubMed

    Barbieri, M Alejandro; Kong, Chen; Chen, Pin-I; Horazdovsky, Bruce F; Stahl, Philip D

    2003-08-22

    Activated epidermal growth factor receptors (EGFRs) recruit intracellular proteins that mediate receptor signaling and endocytic trafficking. Rin1, a multifunctional protein, has been shown to regulate EGFR internalization (1). Here we show that EGF stimulation induces a specific, rapid, and transient membrane recruitment of Rin1 and that recruitment is dependent on the Src homology 2 (SH2) domain of Rin1. Immunoprecipitation of EGFR is accompanied by co-immunoprecipitation of Rin1 in a time- and ligand-dependent manner. Association of Rin1 and specifically the SH2 domain of Rin1 with the EGFR was dependent on tyrosine phosphorylation of the intracellular domain of the EGFR. The recruitment of Rin1, observed by light microscopy, indicated that although initially cytosolic, Rin1 was recruited to both plasma membrane and endosomes following EGF addition. Moreover, the expression of the SH2 domain of Rin1 substantially impaired the internalization of EGF without affecting internalization of transferrin. Finally, we found that Rin1 co-immunoprecipitated with a number of tyrosine kinase receptors but not with cargo endocytic receptors. These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a.

  4. Laparoscopic uterine artery occlusion for symptomatic leiomyomas.

    PubMed

    Lichtinger, Moises; Hallson, Laurey; Calvo, Patricia; Adeboyejo, Ghea

    2002-05-01

    To describe a laparoscopic technique that safely occludes both uterine arteries, overcoming an altered surgical field resulting from scarring and/or uterine leiomyomatous growth. Prospective analysis (Canadian Task Force classification II-2). Nonprofit community hospital. Eight women with leiomyomas with abnormal uterine bleeding, pelvic pain or pressure, and/or anemia. Bilateral laparoscopic retroperitoneal uterine artery occlusion. Occlusion at the initial track of the uterine artery was performed by laparoscopic coated ligature in six patients. In two obese patients with deep retroperitoneal space, vascular clips were placed endoscopically using the same dissecting technique. All patients were discharged within 20 hours after the procedure. All five women with abnormal bleeding reported satisfactory decrease; none reported amenorrhea. Of eight with preoperative pain or pressure, seven reported complete disappearance and one significant relief. All three patients with anemia had normal red cell counts after 1 month. Laparoscopic uterine artery occlusion using a lateral retroperitoneal technique is safe and effective in women with pelvic scarring and altered pelvic anatomy.

  5. Direct observation of mineral–organic composite formation reveals occlusion mechanism

    DOE PAGES

    Cho, Kang Rae; Kim, Yi -Yeoun; Yang, Pengcheng; ...

    2016-01-06

    Manipulation of inorganic materials with organic macromolecules enables organisms to create biominerals such as bones and seashells, where occlusion of biomacromolecules within individual crystals generates superior mechanical properties. Current understanding of this process largely comes from studying the entrapment of micron-size particles in cooling melts. Here, by investigating micelle incorporation in calcite with atomic force microscopy and micromechanical simulations, we show that different mechanisms govern nanoscale occlusion. By simultaneously visualizing the micelles and propagating step edges, we demonstrate that the micelles experience significant compression during occlusion, which is accompanied by cavity formation. This generates local lattice strain, leading to enhancedmore » mechanical properties. Furthermore, these results give new insight into the formation of occlusions in natural and synthetic crystals, and will facilitate the synthesis of multifunctional nanocomposite crystals.« less

  6. Reconstruction-Based Digital Dental Occlusion of the Partially Edentulous Dentition.

    PubMed

    Zhang, Jian; Xia, James J; Li, Jianfu; Zhou, Xiaobo

    2017-01-01

    Partially edentulous dentition presents a challenging problem for the surgical planning of digital dental occlusion in the field of craniomaxillofacial surgery because of the incorrect maxillomandibular distance caused by missing teeth. We propose an innovative approach called Dental Reconstruction with Symmetrical Teeth (DRST) to achieve accurate dental occlusion for the partially edentulous cases. In this DRST approach, the rigid transformation between two symmetrical teeth existing on the left and right dental model is estimated through probabilistic point registration by matching the two shapes. With the estimated transformation, the partially edentulous space can be virtually filled with the teeth in its symmetrical position. Dental alignment is performed by digital dental occlusion reestablishment algorithm with the reconstructed complete dental model. Satisfactory reconstruction and occlusion results are demonstrated with the synthetic and real partially edentulous models.

  7. Reconstruction-based Digital Dental Occlusion of the Partially Edentulous Dentition

    PubMed Central

    Zhang, Jian; Xia, James J.; Li, Jianfu; Zhou, Xiaobo

    2016-01-01

    Partially edentulous dentition presents a challenging problem for the surgical planning of digital dental occlusion in the field of craniomaxillofacial surgery because of the incorrect maxillomandibular distance caused by missing teeth. We propose an innovative approach called Dental Reconstruction with Symmetrical Teeth (DRST) to achieve accurate dental occlusion for the partially edentulous cases. In this DRST approach, the rigid transformation between two symmetrical teeth existing on the left and right dental model is estimated through probabilistic point registration by matching the two shapes. With the estimated transformation, the partially edentulous space can be virtually filled with the teeth in its symmetrical position. Dental alignment is performed by digital dental occlusion reestablishment algorithm with the reconstructed complete dental model. Satisfactory reconstruction and occlusion results are demonstrated with the synthetic and real partially edentulous models. PMID:26584502

  8. Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery.

    PubMed

    Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kawamoto, Chiaki; Uchida, Eiji; Kumita, Shin-Ichiro

    2017-06-01

    To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.

  9. Endovascular management of inferior vena cava filter thrombotic occlusion.

    PubMed

    Branco, Bernardino C; Montero-Baker, Miguel F; Espinoza, Eduardo; Gamero, Maria; Zea-Vera, Rodrigo; Labropoulos, Nicos; Leon, Luis R

    2018-01-01

    Objective Inferior vena cava occlusion is a potentially life-threatening complication related to caval filters. We present our experience with filter-induced inferior vena cava occlusion in order to assess the feasibility, safety, and effectiveness of endovascular management. Methods A retrospective review of all patients undergoing inferior vena cava filter placement over a 60-month study period was performed. From this cohort, a total of 10 cases of inferior vena cava occlusion after filter placement were identified. Demographics, clinical data, procedures, and outcomes were extracted. Patients were followed to the last clinic visit or until they died. Results One-hundred eighty filters were placed by our group practice during the study period. Of those, a total of 10 patients were identified. Overall, there were 7 males; the mean age was 57.1 years (25-78 years). The median time between inferior vena cava filter placement and filter occlusion was 105 days (range 5-4745 days). All patients were clinically symptomatic at the time of their presentation. Nine out of 10 patients were successfully managed endovascularly. Trellis™-8 thrombectomy was the most common endovascular strategy performed ( n = 9). Four patients had balloon angioplasty, two of those with stent placement for chronically occluded inferior vena cava/iliac veins. No thromboembolic complications developed during a median follow-up period of 233 days (range 4-1083 days). Conclusions Endovascular management of inferior vena cava occlusion is feasible, safe, and effective in decreasing thrombus burden in the presence of an inferior vena cava filter. Further studies evaluating long-term inferior vena cava patency and optimal surveillance regimen after endovascular management of filter-related inferior vena cava occlusion are warranted.

  10. The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity.

    PubMed

    Boglev, Yeliz; Wilanowski, Tomasz; Caddy, Jacinta; Parekh, Vishwas; Auden, Alana; Darido, Charbel; Hislop, Nikki R; Cangkrama, Michael; Ting, Stephen B; Jane, Stephen M

    2011-01-15

    The Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays essential roles in epidermal morphogenesis during embryonic development, with deficient mice exhibiting failed skin barrier formation, defective wound repair, and loss of eyelid fusion. Despite sharing significant sequence homology, overlapping expression patterns, and an identical core consensus DNA binding site, the other members of the Grhl family (Grhl1 and -2) fail to compensate for the loss of Grhl3 in these processes. Here, we have employed diverse genetic models, coupled with biochemical studies, to define the inter-relationships of the Grhl factors in epidermal development. We show that Grhl1 and Grhl3 have evolved complete functional independence, as evidenced by a lack of genetic interactions in embryos carrying combinations of targeted alleles of these genes. In contrast, compound heterozygous Grhl2/Grhl3 embryos displayed failed wound repair, and loss of a single Grhl2 allele in Grhl3-null embryos results in fully penetrant eyes open at birth. Expression of Grhl2 from the Grhl3 locus in homozygous knock-in mice corrects the wound repair defect, but these embryos still display a complete failure of skin barrier formation. This functional dissociation is due to unexpected differences in target gene specificity, as both GRHL2 and GRHL3 bind to and regulate expression of the wound repair gene Rho GEF 19, but regulation of the barrier forming gene, Transglutaminase 1 (TGase1), is unique to GRHL3. Our findings define the mechanisms underpinning the unique and cooperative roles of the Grhl genes in epidermal development. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Clinical and microscopic characteristics of canine toxic epidermal necrolysis.

    PubMed

    Banovic, F; Olivry, T; Bazzle, L; Tobias, J R; Atlee, B; Zabel, S; Hensel, N; Linder, K E

    2015-03-01

    Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug reaction, traditionally has been described as full-thickness devitalization of the epidermis with minimal dermal inflammation; however, few reports detail the histologic findings. We characterize the clinical features and histologic variations of 3 canine TEN patients. Clinically, irregular erythematous and purpuric macules evolved into widespread and severely painful erosions. The number of eroded mucosae varied; however, periocular and perilabial mucocutaneous junctions frequently were affected. Thirteen of 17 biopsies were evaluated. Apoptosis at multiple epidermal levels was the most common pattern of epidermal necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis was present less often (7/13 biopsies, 52%). Lymphocytic interface dermatitis was the predominant inflammatory pattern, and intraepidermal lymphocytes, along with fewer histiocytes, were present to some degree in all samples along with lymphocytic satellitosis of apoptotic keratinocytes. The sequence of changes points to lymphocyte-mediated keratinocyte apoptosis as an early step in lesion development with subsequent variation in progression to coagulation necrosis among patients. Histopathologic changes overlapped with those reported for erythema multiforme, in contrast to traditional histologic descriptions of canine TEN. A specific algorithm for assessment of drug causality in epidermal necrolysis (ALDEN) was applied for each patient; carprofen was associated with a probable score for causality in 1 dog. Clinicians should be encouraged to take multiple biopsies in TEN suspect cases as nearly 25% of all biopsies lacked epithelium and were not diagnostic. © The Author(s) 2014.

  12. A role for calcium in the regulation of ATP-binding cassette, sub-family C, member 3 (ABCC3) gene expression in a model of epidermal growth factor-mediated breast cancer epithelial-mesenchymal transition.

    PubMed

    Stewart, Teneale A; Azimi, Iman; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2015-03-13

    Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The mechanisms of intrarenal hemodynamic changes following acute arterial occlusion.

    DOT National Transportation Integrated Search

    1963-10-01

    The hemodynamic response of the kidney to acute arterial occlusion is poorly understood. The purpose of the present study was to determine intrarenal hemodynamic changes in intact and isolated kidneys following arterial occlusion. : The relative role...

  14. [A Project to Reduce the Occlusion Rate in Hemodialysis Arteriovenous Access].

    PubMed

    Huang, Jia-Ling; Jang, Jeng-Fong; Lee, Kun-Feng; Shie, Yu-Ting; Jin, Mei-Hua

    2015-06-01

    Vascular occlusions in patients frequently necessitate that duty nurses work overtime to manage related vascular problems. For patients, vascular occlusions require invasive treatments that are painful, take time to heal, and increase anxiety. Furthermore, vascular occlusions seriously influence the effectiveness of hemodialysis. This project worked to reduce the rates of occlusion from 18.6% to < 15% for hemodialysis arteriovenous grafts (AVGs) and from 5.2% to < 2.6% for arteriovenous fistulas (AVFs). This project was conducted between September 1st, 2012 and July 31th, 2013. Our approach used a retrospective study, literature review, meeting discussions, and data compilation. The four main problems identified as associated with occlusion were: (1) low blood pressure during hemodialysis; (2) successive fistula puncture sites were located too close to one another; (3) abnormal blood flow; and (4) poor moisture control. Our solutions included: 1) adjusting and creating forms; 2) adjusting related nursing procedures; and 3) organizing a related lecture for our department. The occlusion rates of AVG and AVF decreased from 18.6% to 7.4% and 5.2% to 0.9%, respectively. We significantly reduced AVG and AVF occlusion rates by using simple methods such as using a tourniquet ruler, designing big-print, illustrated patient instruction sheets on preventing low blood pressure, creating a simplified fistula puncture site series chart, creating a moisture control card, and scheduling follow-up visits for patients with abnormal blood flow at the OPD. This project provides a reference for other hemodialysis departments.

  15. Effect of occlusal trauma on healing of periapical pathoses: report of two cases.

    PubMed

    Harn, W M; Chen, M C; Chen, Y H; Liu, J W; Chung, C H

    2001-10-01

    To present two clinical cases and demonstrate that occlusal trauma may affect healing of periapical pathoses. Two teeth with periradicular disease did not respond successfully to conventional root canal treatment or endodontic surgery. Occlusal adjustment was finally performed on both cases. After occlusal adjustment, uncomplicated healing and periapical repair occurred in both cases. The findings in these two cases suggest that occlusal trauma may play a role in the healing of periapical pathoses. Occlusal trauma is positively correlated with changes in periodontal tissues. Although experiments in animals have shown that application of forces to teeth will not induce further periodontal destruction, we believe that some failures of root canal treatment may be due to the presence of occlusal trauma modulating the responses of inflamed periapical tissues or apical pathoses with persistent infection.

  16. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    PubMed

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

    PubMed

    Mulder, Gemma M; Nijboer, Willemijn N; Seelen, Marc A; Sandovici, Maria; Bos, Eelke M; Melenhorst, Wynand B W H; Trzpis, Monika; Kloosterhuis, Niels J; Visser, Lydia; Henning, Rob H; Leuvenink, Henri G D; Ploeg, Rutger J; Sunnarborg, Susan W; van Goor, Harry

    2010-06-01

    The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

  18. A Study of Parallelism of the Occlusal Plane and Ala-Tragus Line

    PubMed Central

    Sadr, Katayoun; Sadr, Makan

    2009-01-01

    Background and aims Orientation of the occlusal plane is one of the most important clinical procedures in prostho-dontic rehabilitation of edentulous patients. The aim of this study was to define the best posterior reference point of ala-tragus line for orientation of occlusal plane for complete denture fabrication. Materials and methods Fifty-three dental students (27 females and 26 males) with complete natural dentition and Angel’s Class I occlusal relationship were selected. The subjects were photographed in natural head position while clenching on a Fox plane. After tracing the photographs, the angles between the following lines were measured: the occlusal plane (Fox plane) and the superior border of ala-tragus, the occlusal plane (Fox plane) and the middle of ala-tragus as well as the occlusal plane (Fox plane) and the inferior border of ala-tragus. Descriptive statistics, one sample t-test and independent t-test were used. P value less than 0.05 was considered significant. Results There was no parallelism between the occlusal plane and ala-tragus line with three different posterior ends and one sample t-test showed that the angles between them were significantly different from zero (p<0.05). However, the supe-rior border of ala-tragus line had the lowest mean angle, 1.80° (3.12) and was almost parallel to the occlusal plane. Conclusion The superior border of the tragus is suggested as the posterior reference for ala-tragus line. PMID:23230496

  19. Effect of endovascular reperfusion in relation to site of arterial occlusion.

    PubMed

    Lemmens, Robin; Hamilton, Scott A; Liebeskind, David S; Tomsick, Tom A; Demchuk, Andrew M; Nogueira, Raul G; Marks, Michael P; Jahan, Reza; Gralla, Jan; Yoo, Albert J; Yeatts, Sharon D; Palesch, Yuko Y; Saver, Jeffrey L; Pereira, Vitor M; Broderick, Joseph P; Albers, Gregory W; Lansberg, Maarten G

    2016-02-23

    To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7). The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials. © 2016 American Academy of Neurology.

  20. Psychosocial distress of part-time occlusion in children with intermittent exotropia.

    PubMed

    Kim, Ungsoo Samuel; Park, Subin; Yoo, Hee Jeong; Hwang, Jeong-Min

    2013-01-01

    To evaluate the psychosocial distress of part-time occlusion therapy in intermittent exotropia. A total of 25 children (15 males and 10 females, aged 3 to 7 years, mean age 4.7 years) with intermittent exotropia were enrolled. Behavioral and psychosocial problems were assessed by the Korean Child Behavior Checklist (K-CBCL), which consists of eight categories of withdrawal, somatic problems, depression/anxiety, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior, and the Amblyopia Treatment Index (ATI). The ATI was designed to evaluate the three factors of compliance, adverse effect, and social stigma. The Parenting Stress Index (PSI) is a parent self-report designed to identify potentially dysfunctional parent-child systems. The K-CBCL was obtained before and after occlusion therapy, and the ATI and PSI were taken from parents only after occlusion therapy. We evaluated the change on the K-CBCL and the correlation between the K-CBCL and ATI. The attention problem assessed by the K-CBCL significantly decreased after occlusion therapy. On the ATI, the social stigma was relatively lower than compliance and adverse effect factors (Likert scale 2.64, 3.11, and 3.11, respectively). The somatic problem assessed by the K-CBCL and compliance on the ATI were significantly correlated (p = 0.014). There was no significant change in percentile scores of each subscale (parental dominant scale and child dominant scale) of the PSI. Total stress index before and after occlusion therapy was 97.16 ± 8.38 and 97.00 ± 8.16 respectively (p = 0.382). Occlusion therapy may influence the psychosocial impact on intermittent exotropia patients. Part-time occlusion significantly decreased the attention problem in children with intermittent strabismus. Children with a high somatic problem score on the KCBCL showed poor compliance to the part-time occlusion.

  1. Evidence Relating Subjective Contours and Interpretations Involving Occlusion.

    DTIC Science & Technology

    1981-06-01

    This article describes a patient with visual agnosia who is both unable to make the usual occlusion interpretations and is unable to see subjective...article describes a patient with visual agnosia who is both unable to make the usual occlusion interpretions and is unable to see subjective contours...Dr. Howard Gardner for providing access to the facilities at Boston Veterans Administration Hospital for examination of the agnosia patient J.R. Also

  2. Retinal artery occlusion during carotid artery stenting with distal embolic protection device.

    PubMed

    Kohara, Kotaro; Ishikawa, Tatsuya; Kobayashi, Tomonori; Kawamata, Takakazu

    2018-01-01

    Retinal artery occlusion associated with carotid artery stenosis is well known. Although it can also occur at the time of carotid artery stenting, retinal artery occlusion via the collateral circulation of the external carotid artery is rare. We encountered two cases of retinal artery occlusion that were thought to be caused by an embolus from the external carotid artery during carotid artery stenting with a distal embolic protection device for the internal carotid artery. A 71-year-old man presented with central retinal artery occlusion after carotid artery stenting using the Carotid Guardwire PS and a 77-year-old man presented with branch retinal artery occlusion after carotid artery stenting using the FilterWire EZ. Because additional new cerebral ischaemic lesions were not detected in either case by postoperative diffusion-weighted magnetic resonance imaging, it was highly likely that the debris that caused retinal artery occlusion passed through not the internal carotid artery but collaterals to retinal arteries from the external carotid artery, which was not protected by a distal embolic protection device. It is suggested that a distal protection device for the internal carotid artery alone cannot prevent retinal artery embolisation during carotid artery stenting and protection of the external carotid artery is important to avoid retinal artery occlusion.

  3. The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways*

    PubMed Central

    Kovacevic, Zaklina; Menezes, Sharleen V.; Sahni, Sumit; Kalinowski, Danuta S.; Bae, Dong-Hun; Lane, Darius J. R.; Richardson, Des R.

    2016-01-01

    N-MYC downstream-regulated gene-1 (NDRG1) is a potent growth and metastasis suppressor that acts through its inhibitory effects on a wide variety of cellular signaling pathways, including the TGF-β pathway, protein kinase B (AKT)/PI3K pathway, RAS, etc. To investigate the hypothesis that its multiple effects could be regulated by a common upstream effector, the role of NDRG1 on the epidermal growth factor receptor (EGFR) and other members of the ErbB family, namely human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3), was examined. We demonstrate that NDRG1 markedly decreased the expression and activation of EGFR, HER2, and HER3 in response to the epidermal growth factor (EGF) ligand, while also inhibiting formation of the EGFR/HER2 and HER2/HER3 heterodimers. In addition, NDRG1 also decreased activation of the downstream MAPKK in response to EGF. Moreover, novel anti-tumor agents of the di-2-pyridylketone class of thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, which markedly up-regulate NDRG1, were found to inhibit EGFR, HER2, and HER3 expression and phosphorylation in cancer cells. However, the mechanism involved appeared dependent on NDRG1 for di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, but was independent of this metastasis suppressor for di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone. This observation demonstrates that small structural changes in thiosemicarbazones result in marked alterations in molecular targeting. Collectively, these results reveal a mechanism for the extensive downstream effects on cellular signaling attributed to NDRG1. Furthermore, this study identifies a novel approach for the treatment of tumors resistant to traditional EGFR inhibitors. PMID:26534963

  4. A cephalometric study to determine the plane of occlusion in completely edentulous patients.

    PubMed

    Hindocha, Amit D; Vartak, Vikas N; Bhandari, Aruna J; Dudani, Mohit T

    2013-01-01

    Determination of the plane of occlusion in completely edentulous patients with the help of the ala-tragus line (Camper's plane) may be questioned. An attempt to devise an alternative method to determine the orientation of the plane of occlusion was made. Cephalometric analysis was used to identify whether a correlation exists between the plane of occlusion of dentulous Indian individuals and other stable cranial landmarks. A negative correlation was found to exist between the occlusal Plane-FH plane angle and the porion-nasion-anterior nasal spine (PoNANS) angle. From the derived mathematical correlation, it was concluded that the angulation of the occlusal plane in completely edentulous subjects may be determined by taking a cephalogram at the diagnostic stage. Further, the clinical applicability of the derived mathematical formula (while determining the plane of occlusion) was tested on completely edentulous patients.

  5. An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

    PubMed Central

    El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

    2015-01-01

    We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

  6. Zebrafish grainyhead-like1 is a common marker of different non-keratinocyte epidermal cell lineages, which segregate from each other in a Foxi3-dependent manner

    PubMed Central

    JÄNICKE, MARTINA; RENISCH, BJÖRN; HAMMERSCHMIDT, MATTHIAS

    2012-01-01

    Grainyhead/CP2 transcription factor family members are widely conserved among the animal kingdom and have been implicated in different developmental processes. Thus far, nothing has been known about their roles in zebrafish. Here we identify seven zebrafish grainyhead-like (grhl) / cp2 genes, with focus on grhl1, which is expressed in the periderm and in epidermal ionocyte progenitors, but downregulated when ionocytes differentiate. In addition, expression was detected in other “non-keratinocyte” cell types of the epidermis, such as pvalb8-expressing cells, which according to our lineage tracing experiments are derived from the same pool of progenitor cells like keratinocytes and ionocytes. Antisense morpholino oligonucleotide-based loss-of-function analysis revealed that grhl1 is dispensable for the development and function of all investigated epidermal cell types, but required as a negative regulator of its own transcription during ionocyte differentiation. Knockdown of the transcription factor Foxi3a, which is expressed in a subset of the grhl1 population, caused a loss of ionocytes and a corresponding increase in the number of pvalb8-expressing cells, while leaving the number of grhl1-positive cells unaltered. We propose that grhl1 is a novel common marker of all or most “non-keratinocyte” epidermal progenitors, and that the sub-functionalisation of these cells is regulated by differential positive and negative effects of Foxi3 factors. PMID:19757382

  7. Interdisciplinary treatment of bruxism with an occlusal splint and cognitive behavioral therapy.

    PubMed

    Trindade, Marilene; Orestes-Cardoso, Silvana; de Siqueira, Teresa Cristina

    2015-01-01

    The etiology of bruxism is associated with exogenous factors, such as occlusal interference, stress, and anxiety, as well as endogenous factors involving neurotransmitters of the basal ganglia. Due to the multifactorial etiology of bruxism, interdisciplinary treatment involving professionals from different healthcare fields has been proposed. The aim of the present study was to compare 2 groups of patients with bruxism (11 in each group) treated with either an occlusal splint combined with cognitive behavioral therapy or an occlusal splint alone. Surface electromyography of the masseter and anterior temporal muscles at rest was performed before and after treatment. The mean amplitude of activity of all muscles was lower after treatment, except for the right anterior temporal muscle in the group treated with an occlusal splint alone. Mean amplitudes were greater in the anterior temporal muscles than in the masseter muscles. Significantly greater improvement was found in the group exposed to cognitive behavioral therapy (P < 0.05; analysis of variance and Student t tests). Therefore, the combination of occlusal splint and psychological therapy was more effective at achieving muscle relaxation than occlusal splint use alone.

  8. Reduction of deviation angle during occlusion therapy: in partially accommodative esotropia with moderate amblyopia.

    PubMed

    Chun, Bo Young; Kwon, Soon Jae; Chae, Sun Hwa; Kwon, Jung Yoon

    2007-09-01

    To evaluate changes in ocular alignment in partially accommodative esotropic children age ranged from 3 to 8 years during occlusion therapy for amblyopia. Angle measurements of twenty-two partially accommodative esotropic patients with moderate amblyopia were evaluated before and at 2 years after occlusion therapy. Mean deviation angle with glasses at the start of occlusion treatment was 19.45+/-5.97 PD and decreased to 12.14+/-12.96 PD at 2 years after occlusion therapy (p<0.01). After occlusion therapy, 9 (41%) cases were indications of surgery for residual deviation but if we had planned surgery before occlusion treatment, 18 (82%) of patients would have had surgery. There was a statistical relationship between increase of visual acuity ratio and decrease of deviation angle (r=-0.479, p=0.024). There was a significant reduction of deviation angle of partially accommodative esotropic patients at 2 years after occlusion therapy. Our results suggest that occlusion therapy has an influence on ocular alignment in partially accommodative esotropic patients with amblyopia.

  9. Reduction of Deviation Angle During Occlusion Therapy: In Partially Accommodative Esotropia with Moderate Amblyopia

    PubMed Central

    Chun, Bo Young; Kwon, Soon Jae; Chae, Sun Hwa

    2007-01-01

    Purpose To evaluate changes in ocular alignment in partially accommodative esotropic children age ranged from 3 to 8 years during occlusion therapy for amblyopia. Methods Angle measurements of twenty-two partially accommodative esotropic patients with moderate amblyopia were evaluated before and at 2 years after occlusion therapy. Results Mean deviation angle with glasses at the start of occlusion treatment was 19.45±5.97 PD and decreased to 12.14±12.96 PD at 2 years after occlusion therapy (p<0.01). After occlusion therapy, 9 (41%) cases were indications of surgery for residual deviation but if we had planned surgery before occlusion treatment, 18 (82%) of patients would have had surgery. There was a statistical relationship between increase of visual acuity ratio and decrease of deviation angle (r=-0.479, p=0.024). Conclusions There was a significant reduction of deviation angle of partially accommodative esotropic patients at 2 years after occlusion therapy. Our results suggest that occlusion therapy has an influence on ocular alignment in partially accommodative esotropic patients with amblyopia. PMID:17804922

  10. A comprehensive pathway map of epidermal growth factor receptor signaling

    PubMed Central

    Oda, Kanae; Matsuoka, Yukiko; Funahashi, Akira; Kitano, Hiroaki

    2005-01-01

    The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells. Reflecting this importance, it is one of the best-investigated signaling systems, both experimentally and computationally, and several computational models have been developed for dynamic analysis. A map of molecular interactions of the EGFR signaling system is a valuable resource for research in this area. In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. The map reveals that the overall architecture of the pathway is a bow-tie (or hourglass) structure with several feedback loops. The map is created using CellDesigner software that enables us to graphically represent interactions using a well-defined and consistent graphical notation, and to store it in Systems Biology Markup Language (SBML). PMID:16729045

  11. Transcatheter vessel occlusion: angiographic results versus clinical success

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feldman, L.; Greenfield, A.J.; Waltman, A.C.

    1983-04-01

    A review was made of 219 transcatheter vessel occlusion procedures performed over a ten-year period for control of hemorrhage, tumor palliation, or blood supply redistribution prior to intra-arterial chemotherapy. Complete angiographic success was obtained in 85% of the procedures, with partial success in 8%; complete clinical success was achieved in 53% of patients, with partial success in 23%. the most satisfactory clinical results were obtained with hemorrhagic gastritis and pelvic trauma. Embolizations for duodenal ulcer hemorrhage and transhepatic variceal occlusion were the least clinically successful, although isobutyl-cyanoacrylate appeared to be a significant improvement in angiographic therapy for duodenal ulcer. Themore » overall complication rate was 13%, with one third of the complications clinically silent. These results indicate that transcatheter vessel occlusion is a relatively safe and effective method for control of hemorrhage or tumor infarction.« less

  12. Implications of Natural Occlusion of Ventilated Racks on Ammonia and Sanitation Practices

    PubMed Central

    Creamer, Michelle A; Petty, Joann; Martin, Tara; Bergdall, Valerie; Hickman-Davis, Judy M

    2014-01-01

    Examination of ventilated rat racks prior to semiannual sanitation revealed silicone nozzles and ventilation ports that were partially or completely occluded with granular debris. We subsequently sought to document performance standards for rack sanitation and investigate the effect of ventilation port occlusion on rack function and animal husbandry practices. We hypothesized that individually ventilated cages with occluded airflow would require more frequent cage changes, comparable to those for static cages (that is, every 3 to 4 d). Sprague–Dawley rats were housed under one of 4 conditions: no airflow occlusion, occluded air-supply inlet, occluded air-exhaust outlet, and occlusion of both inlet and outlet. Cages were changed when daily ammonia concentration exceeded 20 ppm or after 14 d had elapsed. Most cages with unoccluded or partial airflow occlusion remained below the 20 ppm limit until day 12 or 13. Cages with occlusion of both inlet and outlet exceeded 20 ppm ammonia by as early as day 5. Airflow was significantly lower in cages with occlusion of both inlet and outlet airflow. Weekly inspection revealed that occlusion of ventilation ports was detectable by 3 mo after semiannual sanitation. This study demonstrates that silicone nozzles should be removed prior to rack sanitation to improve the effectiveness of cleaning ventilation ports and nozzles. While the rack is in use, silicone nozzles and ventilation ports should be inspected regularly to identify occlusion that is likely to diminish environmental quality in the cage. Intracage ammonia levels are significantly higher when both inlet and outlet airflow are occluded. PMID:24602544

  13. Implications of natural occlusion of ventilated racks on ammonia and sanitation practices.

    PubMed

    Creamer, Michelle A; Petty, Joann; Martin, Tara; Bergdall, Valerie; Hickman-Davis, Judy M

    2014-03-01

    Examination of ventilated rat racks prior to semiannual sanitation revealed silicone nozzles and ventilation ports that were partially or completely occluded with granular debris. We subsequently sought to document performance standards for rack sanitation and investigate the effect of ventilation port occlusion on rack function and animal husbandry practices. We hypothesized that individually ventilated cages with occluded airflow would require more frequent cage changes, comparable to those for static cages (that is, every 3 to 4 d). Sprague-Dawley rats were housed under one of 4 conditions: no airflow occlusion, occluded air-supply inlet, occluded air-exhaust outlet, and occlusion of both inlet and outlet. Cages were changed when daily ammonia concentration exceeded 20 ppm or after 14 d had elapsed. Most cages with unoccluded or partial airflow occlusion remained below the 20 ppm limit until day 12 or 13. Cages with occlusion of both inlet and outlet exceeded 20 ppm ammonia by as early as day 5. Airflow was significantly lower in cages with occlusion of both inlet and outlet airflow. Weekly inspection revealed that occlusion of ventilation ports was detectable by 3 mo after semiannual sanitation. This study demonstrates that silicone nozzles should be removed prior to rack sanitation to improve the effectiveness of cleaning ventilation ports and nozzles. While the rack is in use, silicone nozzles and ventilation ports should be inspected regularly to identify occlusion that is likely to diminish environmental quality in the cage. Intracage ammonia levels are significantly higher when both inlet and outlet airflow are occluded.

  14. The role of the epidermis in the control of scarring: evidence for mechanism of action for silicone gel.

    PubMed

    Tandara, Andrea A; Mustoe, Thomas A

    2008-10-01

    Hypertrophic scars can be reduced by the application of silicone dressing; however, the detailed mechanism of silicone action is still unknown. It is known that silicone gel sheets cause a hydration of the epidermal layer of the skin. An in vitro co-culture experiment has shown that hydration of keratinocytes has a suppressive effect on the metabolism of the underlying fibroblasts resulting in reduced collagen deposition. We tested the hypothesis that silicone sheeting in vivo has a beneficial effect on scarring by reducing keratinocyte stimulation, with a resulting decrease in dermal thickness, hence scar hypertrophy. Silicone adhesive gel sheets were applied to scars in our rabbit ear model of hypertrophic scarring 14 days postwounding for a total of 16 days. Scarring was measured in this model by the scar elevation index (SEI), a ratio of the area of newly formed dermis to the area of the dermis of unwounded skin, and the epidermal thickness index (ETI), a ratio of the averaged epidermal height of the scar to the epidermal thickness of normal epidermis. Specific staining [anti-PCNA (proliferating cell nuclear antigen) and Masson trichrome] was performed to reveal differences in scar morphology. SEIs were significantly reduced after silicone gel sheet application versus untreated scars corresponding to a 70% reduction in scar hypertrophy. Total occlusion reduced scar hypertrophy by 80% compared to semi-occlusion. ETIs of untreated scars were increased by more than 100% compared to uninjured skin. Silicone gel treatment significantly reduced epidermal thickness by more than 30%. Our findings demonstrate that 2 weeks of silicone gel application at a very early onset of scarring reduces dermal and epidermal thickness which appears to be due to a reduction in keratinocyte stimulation. Oxygen can be ruled out as a mechanism of action of silicone occlusive treatment. Hydration of the keratinocytes seems to be the key stimulus.

  15. SNPing at the Epidermal Barrier.

    PubMed

    Kelsell, David P; Byrne, Carolyn

    2011-08-01

    Filaggrin variants are well-established risk factors for atopic eczema (AE). Recent studies suggest additional epidermal differentiation complex (EDC) gene associations with AE. In this issue, Marenholz and colleagues confirm this prediction and show that a small proline-rich protein 3 (SPRR3) variant confers susceptibility to AE. This finding suggests that further genetic and functional characterization of SPRR3 should be performed in patients with AE.

  16. Repeated arterial occlusion, delta-opioid receptor (DOR) plasticity and vagal transmission within the sinoatrial node of the anesthetized dog.

    PubMed

    Deo, Shekhar H; Barlow, Matthew A; Gonzalez, Leticia; Yoshishige, Darice; Caffrey, James L

    2009-01-01

    Brief interruptions in coronary blood flow precondition the heart, engage delta-opioid receptor (DOR) mechanisms and reduce the damage that typically accompanies subsequent longer coronary occlusions. Repeated short occlusions of the sinoatrial (SA) node artery progressively raised nodal methionine-enkephalin-arginine-phenylalanine (MEAP) and improved vagal transmission during subsequent long occlusions in anesthetized dogs. The DOR type-1 (DOR-1) antagonist, BNTX reversed the vagotonic effect. Higher doses of enkephalin interrupted vagal transmission through a DOR-2 mechanism. The current study tested whether the preconditioning (PC) protocol, the later occlusion or a combination of both was required for the vagotonic effect. The study also tested whether evolving vagotonic effects included withdrawal of competing DOR-2 vagolytic influences. Vagal transmission progressively improved during successive SA nodal artery occlusions. The vagotonic effect was absent in sham animals and after DOR-1 blockade. After completing the PC protocol, exogenously applied vagolytic doses of MEAP reduced vagal transmission under both normal and occluded conditions. The magnitude of these DOR-2 vagolytic effects was small compared to controls and repeated MEAP challenges rapidly eroded vagolytic responses further. Prior DOR-1 blockade did not alter the PC mediated, progressive loss of DOR-2 vagolytic responses. In conclusion, DOR-1 vagotonic responses evolved from signals earlier in the PC protocol and erosion of competing DOR-2 vagolytic responses may have contributed to an unmasking of vagotonic responses. The data support the hypothesis that PC and DOR-2 stimulation promote DOR trafficking, and down regulation of the vagolytic DOR-2 phenotype in favor of the vagotonic DOR-1 phenotype. DOR-1 blockade may accelerate the process by sequestering newly emerging receptors.

  17. CPK3-phosphorylated RhoGDI1 is essential in the development of Arabidopsis seedlings and leaf epidermal cells

    PubMed Central

    Wu, Yan

    2013-01-01

    The regulation of Rho of plants (ROP) in morphogenesis of leaf epidermal cells has been well studied, but the roles concerning regulators of ROPs such as RhoGDIs are poorly understood. This study reports that AtRhoGDI1 (GDI1) acts as a versatile regulator to modulate development of seedlings and leaf pavement cells. In mutant gdi1, leaf pavement cells showed shorter lobes in comparison with those in wild type. In GDI1-14 seedlings (GDI1-overexpression line) the growth of lobes in pavement cells was severely suppressed and the development of seedlings was altered. These results indicate that GDI1 plays an essential role in morphogenesis of epidermal pavement cells through modulating the ROP signalling pathways. The interaction between GDI1 and ROP2 or ROP6 was detected in the leaf pavement cells using FRET analysis. Dominant negative, not constitutively active, DN-rop6 could weaken the effect caused by overexpression of GDI1; because the pleiotropic phenotype of GDI1-14 plants was eliminated in the hybrid line GDI1-14 DN-rop6. GDI1 could be phosphorylated by CPK3. Three conserved Ser/Thr residues in GDI1 were determined as targeted amino acids for CPK3. Overexpression of GDI1(3D), not GDI1(3A), could rescue the abnormal growth phenotypes of gdi1-1 seedlings, demonstrating the impact of GDI1 phosphorylation in the development of Arabidopsis. In summary, these results suggest that GDI1 regulation in morphogenesis of seedlings and leaf pavement cells could be undergone through modulating the ROP signalling pathways and the phosphorylation of GDI1 by CPK3 was required for the developmental modulation in Arabidopsis. PMID:23846874

  18. Visual Acuity Improvement in Continuous vs Divided Occlusion in Anisometropic Amblyopia

    PubMed Central

    Irfani, Irawati; Feriyanto, Feri; Oktarima, Primawita; Kartasasmita, Arief

    2018-01-01

    Purpose: To compare visual acuity improvement between continuous and split part-time occlusion for the treatment of moderate and severe anisometropic amblyopia. Methods: Randomised clinical trials in 6 – 13 y.o children with moderate and severe anisometropic amblyopia. Each patient was consecutively selected with continuous or split part-time occlusion. Best corrected visual acuity’s improvement was followed up to six weeks and statistical data were analyzed using chi square and unpaired t-test. Results: Best corrected visual acuity’s improvement was comparable between continuous and split part-time occlusion (0.20±0.27 vs 0.21±0.25; p = 0.79). Conclusion: Split part-time occlusion may be considered as an alternative treatment for moderate and severe anisometropic amblyopia treatment. PMID:29515681

  19. Occlus-o-Guide® versus Andresen activator appliance: neuromuscular evaluation.

    PubMed

    Farronato, Giampietro; Giannini, Lucia; Galbiati, Guido; Grillo, Elena; Maspero, Cinzia

    2013-05-20

    The aim of the present study was to assess the muscular variations at the electromyography (EMG) level for the anterior temporalis muscles and masseter muscles during treatment with Occlus-o-Guide® and Andresen activator appliances. Eighty-two patients (35 males and 47 females) aged between 8 and 12 years (mean age, 10.5±0.8 years) participated in the study. Fifty patients underwent treatment with an Occlus-o-Guide® and 32 patients with an Andresen activator. All patients underwent EMG examination using a Freely EMG (De Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of appliance use. Statistical analysis showed that both at T0 and T2, the percent overlapping coefficient (POC) of the anterior temporalis muscles was not statistically different between the appliance groups. At T0, the POC of the masseter muscles was significantly lower for the Andresen appliance as compared to the Occlus-o-Guide® (p=0.02), while at T2 this significance was lost. At insertion of an appliance, all patients show neuromuscular balance that does not correspond to orthognathic occlusion. Both appliances work by creating muscular imbalance. With the appliances in situ, EMG responses were generally analogous for the Occlus-o-Guide® and the Andresen activator; however, the imbalance was greater and the recovery of the orthological muscular balance was slower in patients under treatment with the Andresen activator as compared to those with the Occlus-o-Guide®.

  20. Recent advances in managing vascular occlusions in the cardiac catheterization laboratory

    PubMed Central

    Qureshi, Athar M.; Mullins, Charles E.; Latson, Larry A.

    2018-01-01

    Vascular occlusions continue to be a significant cause of morbidity and mortality. The management of vascular occlusions in patients is complex, requiring specialized expertise in the cardiac catheterization laboratory and from other disciplines. Knowledge of currently available tools at the operator’s disposal is important to optimize the success of these procedures. In this review, we discuss some of the recent advances in recanalization procedures of vascular occlusions and thrombotic lesions in the cardiac catheterization laboratory. PMID:29770200

  1. Electro-acupuncture up-regulates astrocytic MCT1 expression to improve neurological deficit in middle cerebral artery occlusion rats.

    PubMed

    Lu, Yan; Zhao, Haijun; Wang, Yuan; Han, Bingbing; Wang, Tong; Zhao, Hong; Cui, Kemi; Wang, Shijun

    2015-08-01

    Cerebral ischemia is one of the common diseases treated by electro-acupuncture (EA). Although the clinical efficacy has been widely affirmed, the mechanisms of action leading to the health benefits are not understood. In this study, the role of EA in modulating the lactate energy metabolism and lactate transportation was explored on the middle cerebral artery occlusion (MCAO) ischemic rat model. Repeated EA treatments once daily for 7 days were applied to the MCAO rats and neurological function evaluation was performed. Brain tissues were harvested for lactate concentration examination, immunohistochemical staining, Western blot and qRT-PCR analyses for the expressions of lactate transporter (monocarboxylate transporter 1, MCT1) and glial fibrillary acidic protein (GFAP). The animal behavioral tests showed that the 7-day EA treatments significantly promoted the recovery of neurological deficits in the MCAO rats, which correlated with the enhanced lactate energy metabolism in the ischemic brain. In the cortical ischemic area of the MCAO rats, EA treatments led to the activation of astrocytes, and induced a further increase of lactate transporter (monocarboxylate transporter 1, MCT1) expression in astrocytes at both protein and mRNA levels. Our results suggest that the EA treatments activated lactate metabolism in the resident astrocytes around the ischemic area and up-regulated the expression of MCT1 in these astrocytes which facilitated the transfer of intracellular lactate to extracellular domain to be utilized by injured neurons to improve the neurological deficit. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

    PubMed Central

    Walko, Gernot; Woodhouse, Samuel; Pisco, Angela Oliveira; Rognoni, Emanuel; Liakath-Ali, Kifayathullah; Lichtenberger, Beate M.; Mishra, Ajay; Telerman, Stephanie B.; Viswanathan, Priyalakshmi; Logtenberg, Meike; Renz, Lisa M.; Donati, Giacomo; Quist, Sven R.; Watt, Fiona M.

    2017-01-01

    Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2. PMID:28332498

  3. Occlusion and Temporomandibular Function among Subjects with Mandibular Distal Extension Removable Partial Dentures

    PubMed Central

    Creugers, N. H. J.; Witter, D. J.; Van 't Spijker, A.; Gerritsen, A. E.; Kreulen, C. M.

    2010-01-01

    Objective. To quantify effects on occlusion and temporomandibular function of mandibular distal extension removable partial dentures in shortened dental arches. Methods. Subjects wearing mandibular extension removable partial dentures (n = 25) were compared with subjects with shortened dental arches without extension (n = 74) and with subjects who had worn a mandibular extension removable partial denture in the past (n = 19). Subjects with complete dentitions (n = 72) were controls. Data were collected at baseline and at 3-, 6-, and 9-year observations. Results. Occlusal activity in terms of reported awareness of bruxism and occlusal tooth wear of lower anterior teeth did not differ significantly between the groups. In contrast, occlusal tooth wear of premolars in shortened dental arches with or without extension dentures was significantly higher than in the controls. Differences amongst groups with respect to signs and symptoms related to temporomandibular disorders were not found. Occlusal support of the dentures did not influence anterior spatial relationship. Occlusal contacts of the denture teeth decreased from 70% for second premolars via 50% for first molars, to 30% for second molars. Conclusions. Mandibular distal extension removable partial dentures in moderate shortened dental arches had no effects on occlusion and temporomandibular function. PMID:20671961

  4. Occlusal enamel complexity in middle miocene to holocene equids (Equidae: Perissodactyla) of North America.

    PubMed

    Famoso, Nicholas A; Davis, Edward Byrd

    2014-01-01

    Four groups of equids, "Anchitheriinae," Merychippine-grade Equinae, Hipparionini, and Equini, coexisted in the middle Miocene, but only the Equini remains after 16 Myr of evolution and extinction. Each group is distinct in its occlusal enamel pattern. These patterns have been compared qualitatively but rarely quantitatively. The processes influencing the evolution of these occlusal patterns have not been thoroughly investigated with respect to phylogeny, tooth position, and climate through geologic time. We investigated Occlusal Enamel Index, a quantitative method for the analysis of the complexity of occlusal patterns. We used analyses of variance and an analysis of co-variance to test whether equid teeth increase resistive cutting area for food processing during mastication, as expressed in occlusal enamel complexity, in response to increased abrasion in their diet. Results suggest that occlusal enamel complexity was influenced by climate, phylogeny, and tooth position through time. Occlusal enamel complexity in middle Miocene to Modern horses increased as the animals experienced increased tooth abrasion and a cooling climate.

  5. Occlusal status and prevalence of occlusal malocclusion traits among 9-year-old schoolchildren.

    PubMed

    Lux, Christopher J; Dücker, Britta; Pritsch, Maria; Komposch, Gerda; Niekusch, Uwe

    2009-06-01

    The aim of this study was to provide detailed information concerning clinically relevant occlusal traits and the prevalence of occlusal anomalies in an orthodontically relevant period of dental development. Four hundred and ninety-four German schoolchildren (237 males and 257 females), median age 9 years, were orthodontically examined. Overjet and overbite were measured to the nearest 0.5 mm, and sagittal molar relationships were registered clinically to the nearest quarter unit. In addition, crossbites, scissor bites, and midline displacements were evaluated. Descriptive statistics was complemented by testing gender differences and differences between groups with Class I and Class II anomalies (Mann-Whitney U-test) as well as a statistical evaluation of differences between the three dental stages (Kruskal-Wallis test). Overjet exhibited an extreme range between -2 and 12 mm (median values 3-3.5 mm). An increased overjet was more prevalent than a reduced or reverse overjet, and a severely increased overjet greater than 6 mm was a common finding affecting around 5-10 per cent of the children. Similarly, overbite showed considerable variations of between -1 and 9 mm (medians 3-3.5 mm) and males exhibited a significantly larger overbite than females. In Class II malocclusion subjects, overbite was significantly enlarged (on average between 0.5 and 1 mm) when compared with those with a Class I malocclusion. Traumatic contact of the gingiva affected every 14th child. A Class II molar relationship of three-quarter units or more was a frequent finding affecting more than one child in five. In addition, at 9 years of age, 3 per cent of the children exhibited a Class III molar relationship of at least a half unit. The wide range of orthodontically relevant occlusal traits found in the present study underlines the need for orthodontic screening at 9 years of age (or earlier).

  6. Relative contributions of occlusion, maximum bite force, and chewing cycle kinematics to masticatory performance.

    PubMed

    Lepley, Casey R; Throckmorton, Gaylord S; Ceen, Richard F; Buschang, Peter H

    2011-05-01

    The purpose of this study was to explore the contributions of occlusion, maximum bite force, and chewing cycle kinematics to masticatory performance. A prospective cross-sectional study was performed on 30 subjects with Class I occlusion. Masticatory performance was measured with the test food Cuttersil (Heraeus Kulzer, South Bend, Ind) and the fractional-sieve technique. Blu-Mousse (Parkell Biomaterials, Farmingdale, NY) bite registrations were used to measure occlusal contact areas. The American Board of Orthodontics occlusal discrepancies were measured on the subjects' dental models. Maximum bite forces were recorded with a custom transducer, and 3-dimensional chewing cycle kinematics were tracked with an opto-electric computer system and Optotrak software (Northern Digital, Waterloo, Ontario, Canada). Masticatory performance was most closely correlated with occlusal contact area, indicating larger contact areas in subjects with better performance. Occlusal contact area and occlusal discrepancies were also related to bite force and chewing cycle kinematics. Maximum bite force was positively related with masticatory performance. Although masticatory performance is related, both directly and indirectly, to a number of morphologic and functional factors, it is most closely related to occlusal factors. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  7. Mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors sensitize reduced glucocorticoid response mediated by TNFalpha in human epidermal keratinocytes (HaCaT).

    PubMed

    Onda, Kenji; Nagashima, Masahiro; Kawakubo, Yo; Inoue, Shota; Hirano, Toshihiko; Oka, Kitaro

    2006-12-08

    Glucocorticoids (GCs) are essential drugs administered topically or systematically for the treatment of autoimmune skin diseases such as pemphigus. However, a certain proportion of patients does not respond well to GCs. Although studies on the relationship between cytokines and GC insensitivity in local tissues have attracted attention recently, little is known about the underlying mechanism(s) for GC insensitivity in epidermal keratinocytes. Here, we report that tumor necrosis factor (TNF) alpha reduces GC-induced transactivation of endogenous genes as well as a reporter plasmid which contains GC responsive element (GRE) in human epidermal keratinocyte cells (HaCaT). The GC insensitivity by TNFalpha was not accompanied by changes in mRNA expressions of GR isoforms (alpha or beta). However, we observed that mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors (PD98059 and U0126) significantly sensitized the GC-induced transactivation of anti-inflammatory genes (glucocorticoid-induced leucine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP)-1) and FK506 binding protein (FKBP) 51 gene in the presence of TNFalpha. Additionally, we observed that TNFalpha reduced prednisolone (PSL)-dependent nuclear translocation of GR, which was restored by pre-treatment of MEK-1 inhibitors. This is the first study demonstrating a role of the MEK-1/ERK cascade in TNFalpha-mediated GC insensitivity. Our data suggest that overexpression of TNFalpha leads to topical GC insensitivity by reducing GR nuclear translocation in keratinocytes, and our findings also suggest that inhibiting the MEK-1/ERK cascade may offer a therapeutic potential for increasing GC efficacy in epidermis where sufficient inflammatory suppression is required.

  8. Management of Retinal Vein Occlusion, Who Is Responsible?

    PubMed

    Aghamirsalim, Mohamadreza; Sorbi, Reza; Naderian, Mohammadreza; Cugati, Sudha; Shahsuvaryan, Marianne Levon; Ghazizadeh Hashemi, Maryam

    2016-11-01

    Retinal vein occlusion (RVO) is a common retinal vascular occlusive disorder and is associated with a variety of systemic risk factors. The aim of this study was to investigate whether the underlying diseases were evaluated and managed appropriately by ophthalmologists. We performed a study of 1344 patients with retinal vein occlusion (RVO). Patients were evaluated with a questionnaire including ten closed questions to determine whether ophthalmologists evaluated and informed their patients about the underlying systemic diseases. None of the patients' homocysteine levels were measured. Only a small percentage of the patients were asked about the history of thrombotic diseases or family history of thrombotic diseases. We believe that most ophthalmologists are still not entirely convinced of their responsibility of managing the underlying predisposing factors of RVO. Ophthalmologists should either manage or engage other healthcare providers in the management of RVO to guarantee the patient the best care.

  9. The dental literature on occlusion and myogenous orofacial pain: application of critical thinking.

    PubMed

    Solow, Roger Alan

    2016-09-01

    To enhance the reader's critical thinking when reading the dental literature on the relationship of occlusion and myogenous orofacial pain (MOP). Representative journal articles and systematic reviews from the dental literature confirming and denying a relationship of occlusion to MOP were analyzed and reviewed. Studies using computerized occlusal analysis (COA) consistently find a relationship of the occlusion to MOP. Studies that do not confirm this relationship have problems with invalid primary source conclusions, unstated assumptions, bias, and errors in logic that disqualify their conclusion. This review explains four categories of problems with the dental literature that denies occlusion has a relationship with MOP. When the reader understands these examples of flaws in this literature, they can apply this critical thinking to future studies. Correct interpretation of the literature on occlusion and MOP requires a foundation of basic and clinical scientific knowledge as well as an understanding of the details of the primary source articles.

  10. Ambient occlusion effects for combined volumes and tubular geometry.

    PubMed

    Schott, Mathias; Martin, Tobias; Grosset, A V Pascal; Smith, Sean T; Hansen, Charles D

    2013-06-01

    This paper details a method for interactive direct volume rendering that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube-shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The algorithm extends the recently presented the directional occlusion shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. Stream tube geometries are computed using an effective spline-based interpolation and approximation scheme that avoids self-intersection and maintains coherent orientation of the stream tube segments to avoid surface deforming twists. Furthermore, strategies to reduce the geometric and specular aliasing of the stream tubes are discussed.

  11. Ambient Occlusion Effects for Combined Volumes and Tubular Geometry

    PubMed Central

    Schott, Mathias; Martin, Tobias; Grosset, A.V. Pascal; Smith, Sean T.; Hansen, Charles D.

    2013-01-01

    This paper details a method for interactive direct volume rendering that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube-shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The algorithm extends the recently presented the directional occlusion shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. Stream tube geometries are computed using an effective spline-based interpolation and approximation scheme that avoids self-intersection and maintains coherent orientation of the stream tube segments to avoid surface deforming twists. Furthermore, strategies to reduce the geometric and specular aliasing of the stream tubes are discussed. PMID:23559506

  12. Effect of occlusal interference on habitual activity of human masseter.

    PubMed

    Michelotti, A; Farella, M; Gallo, L M; Veltri, A; Palla, S; Martina, R

    2005-07-01

    It has been suggested that occlusal interference may increase habitual activity in the jaw muscles and may lead to temporomandibular disorders (TMD). We tested these hypotheses by means of a double-blind randomized crossover experiment carried out on 11 young healthy females. Strips of gold foil were glued either on a selected occlusal contact area (active interference) or on the vestibular surface of the same tooth (dummy interference) and left for 8 days each. Electromyographic masseter activity was recorded in the natural environment by portable recorders under interference-free, dummy-interference, and active-interference conditions. The active occlusal interference caused a significant reduction in the number of activity periods per hour and in their mean amplitude. The EMG activity did not change significantly during the dummy-interference condition. None of the subjects developed signs and/or symptoms of TMD throughout the whole study, and most of them adapted fairly well to the occlusal disturbance.

  13. Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study.

    PubMed

    Overbeek, Maria J; Boonstra, Anco; Voskuyl, Alexandre E; Vonk, Madelon C; Vonk-Noordegraaf, Anton; van Berkel, Maria P A; Mooi, Wolter J; Dijkmans, Ben A C; Hondema, Laurens S; Smit, Egbert F; Grünberg, Katrien

    2011-04-14

    Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation. Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity. All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals. PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity

  14. Barrier Requirements as the Evolutionary “Driver” of Epidermal Pigmentation in Humans

    PubMed Central

    ELIAS, PETER M.; MENON, GOPINATHAN; WETZEL, BRUCE K.; WILLIAMS, JOHN (JACK) W.

    2011-01-01

    Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand-alone hypotheses. Accordingly, we assessed instead whether xeric- and UV-B-induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have “driven” the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [≈1.5–0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV-B, correlating with genetic evidence that pigment developed ≈1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more-acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte-derived signals (stem cell factor⇒KIT; FOXn1⇒FGF2; IL-1α, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. PMID:20209486

  15. Single-cell gene expression profiling reveals functional heterogeneity of undifferentiated human epidermal cells

    PubMed Central

    Tan, David W. M.; Jensen, Kim B.; Trotter, Matthew W. B.; Connelly, John T.; Broad, Simon; Watt, Fiona M.

    2013-01-01

    Human epidermal stem cells express high levels of β1 integrins, delta-like 1 (DLL1) and the EGFR antagonist LRIG1. However, there is cell-to-cell variation in the relative abundance of DLL1 and LRIG1 mRNA transcripts. Single-cell global gene expression profiling showed that undifferentiated cells fell into two clusters delineated by expression of DLL1 and its binding partner syntenin. The DLL1+ cluster had elevated expression of genes associated with endocytosis, integrin-mediated adhesion and receptor tyrosine kinase signalling. Differentially expressed genes were not independently regulated, as overexpression of DLL1 alone or together with LRIG1 led to the upregulation of other genes in the DLL1+ cluster. Overexpression of DLL1 and LRIG1 resulted in enhanced extracellular matrix adhesion and increased caveolin-dependent EGFR endocytosis. Further characterisation of CD46, one of the genes upregulated in the DLL1+ cluster, revealed it to be a novel cell surface marker of human epidermal stem cells. Cells with high endogenous levels of CD46 expressed high levels of β1 integrin and DLL1 and were highly adhesive and clonogenic. Knockdown of CD46 decreased proliferative potential and β1 integrin-mediated adhesion. Thus, the previously unknown heterogeneity revealed by our studies results in differences in the interaction of undifferentiated basal keratinocytes with their environment. PMID:23482486

  16. Comparison of occlusion break responses and vacuum rise times of phacoemulsification systems.

    PubMed

    Sharif-Kashani, Pooria; Fanney, Douglas; Injev, Val

    2014-07-30

    Occlusion break surge during phacoemulsification cataract surgery can lead to potential surgical complications. The purpose of this study was to quantify occlusion break surge and vacuum rise time of current phacoemulsification systems used in cataract surgery. Occlusion break surge at vacuum pressures between 200 and 600 mmHg was assessed with the Infiniti® Vision System, the WhiteStar Signature® Phacoemulsification System, and the Centurion® Vision System using gravity-fed fluidics. Centurion Active FluidicsTM were also tested at multiple intraoperative pressure target settings. Vacuum rise time was evaluated for Infiniti, WhiteStar Signature, Centurion, and Stellaris® Vision Enhancement systems. Rise time to vacuum limits of 400 and 600 mmHg was assessed at flow rates of 30 and 60 cc/minute. Occlusion break surge was analyzed by 2-way analysis of variance. The Centurion system exhibited substantially less occlusion break surge than the other systems tested. Surge area with Centurion Active Fluidics was similar to gravity fluidics at an equivalent bottle height. At all Centurion Active Fluidics intraoperative pressure target settings tested, surge was smaller than with Infiniti and WhiteStar Signature. Infiniti had the fastest vacuum rise time and Stellaris had the slowest. No system tested reached the 600-mmHg vacuum limit. In this laboratory study, Centurion had the least occlusion break surge and similar vacuum rise times compared with the other systems tested. Reducing occlusion break surge may increase safety of phacoemulsification cataract surgery.

  17. Filamin A Modulates Kinase Activation and Intracellular Trafficking of Epidermal Growth Factor Receptors in Human Melanoma Cells

    PubMed Central

    Fiori, Jennifer L.; Zhu, Tie-Nian; O'Connell, Michael P.; Hoek, Keith S.; Indig, Fred E.; Frank, Brittany P.; Morris, Christa; Kole, Sutapa; Hasskamp, Joanne; Elias, George; Weeraratna, Ashani T.; Bernier, Michel

    2009-01-01

    The actin-binding protein filamin A (FLNa) affects the intracellular trafficking of various classes of receptors and has a potential role in oncogenesis. However, it is unclear whether FLNa regulates the signaling capacity and/or down-regulation of the activated epidermal growth factor receptor (EGFR). Here it is shown that partial knockdown of FLNa gene expression blocked ligand-induced EGFR responses in metastatic human melanomas. To gain greater insights into the role of FLNa in EGFR activation and intracellular sorting, we used M2 melanoma cells that lack endogenous FLNa and a subclone in which human FLNa cDNA has been stably reintroduced (M2A7 cells). Both tyrosine phosphorylation and ubiquitination of EGFR were significantly lower in epidermal growth factor (EGF)-stimulated M2 cells when compared with M2A7 cells. Moreover, the lack of FLNa interfered with EGFR interaction with the ubiquitin ligase c-Cbl. M2 cells exhibited marked resistance to EGF-induced receptor degradation, which was very active in M2A7 cells. Despite comparable rates of EGF-mediated receptor endocytosis, internalized EGFR colocalized with the lysosomal marker lysosome-associated membrane protein-1 in M2A7 cells but not M2 cells, in which EGFR was found to be sequestered in large vesicles and subsequently accumulated in punctated perinuclear structures after EGF stimulation. These results suggest the requirement of FLNa for efficient EGFR kinase activation and the sorting of endocytosed receptors into the degradation pathway. PMID:19213840

  18. Occlusion assessment of intracranial aneurysms treated with the WEB device.

    PubMed

    Caroff, Jildaz; Mihalea, Cristian; Tuilier, Titien; Barreau, Xavier; Cognard, Christophe; Desal, Hubert; Pierot, Laurent; Arnoux, Armelle; Moret, Jacques; Spelle, Laurent

    2016-09-01

    The Woven EndoBridge (WEB) system is an innovative device under evaluation for its capacity to treat wide-neck bifurcation intracranial aneurysms. The purpose of this study is to evaluate the use of the different occlusion scales available in clinical practice. Seven WEB-experienced neurointerventionalists were provided with 30 angiographic follow-up data sets and asked to grade each evaluation point according to the Bicêtre Occlusion Scale Score (BOSS), firstly based on DSA images only then using additional C-Arm VasoCT analysis. This BOSS evaluation was then converted into the WEB Occlusion Scale (WOS) and into a dichotomized scale (complete occlusion or not). To estimate the inter-rater agreement among the seven raters, an overall kappa coefficient [1] and its standard error (SE) were computed. Using the five-grade BOSS, raters showed "moderate" agreement (kappa = 0.56). Using the three-grade WOS, agreement appeared slightly better (kappa = 0.59). Strongest inter-rater agreement was observed with a dichotomized version of the scale (complete occlusion or not), which enabled an "almost perfect" agreement (kappa = 0.88). VasoCT consistently enhanced the agreement particularly with regards depicting intra-WEB residual filling. The WOS is a consistent means to angiographically evaluate the WEB device efficiency. But the five-grade BOSS scale allows to identify aneurysm subgroups with differing risks of recurrence and/or rehemorrhage, which needs to be separated especially at the initial phase of evaluation of this innovative device. The additional use of VasoCT allows better inter-rater agreement in evaluating occlusion and specially in depicting intra-WEB persistent filling.

  19. Occlus-o-Guide® versus Andresen activator appliance: neuromuscular evaluation

    PubMed Central

    2013-01-01

    Background The aim of the present study was to assess the muscular variations at the electromyography (EMG) level for the anterior temporalis muscles and masseter muscles during treatment with Occlus-o-Guide® and Andresen activator appliances. Methods Eighty-two patients (35 males and 47 females) aged between 8 and 12 years (mean age, 10.5 ± 0.8 years) participated in the study. Fifty patients underwent treatment with an Occlus-o-Guide® and 32 patients with an Andresen activator. All patients underwent EMG examination using a Freely EMG (De Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of appliance use. Results Statistical analysis showed that both at T0 and T2, the percent overlapping coefficient (POC) of the anterior temporalis muscles was not statistically different between the appliance groups. At T0, the POC of the masseter muscles was significantly lower for the Andresen appliance as compared to the Occlus-o-Guide® (p = 0.02), while at T2 this significance was lost. Conclusions At insertion of an appliance, all patients show neuromuscular balance that does not correspond to orthognathic occlusion. Both appliances work by creating muscular imbalance. With the appliances in situ, EMG responses were generally analogous for the Occlus-o-Guide® and the Andresen activator; however, the imbalance was greater and the recovery of the orthological muscular balance was slower in patients under treatment with the Andresen activator as compared to those with the Occlus-o-Guide®. PMID:24325935

  20. Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30.

    PubMed

    Quinn, Jeffrey A; Graeber, C Thomas; Frackelton, A Raymond; Kim, Minsoo; Schwarzbauer, Jean E; Filardo, Edward J

    2009-07-01

    Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERalpha and ERbeta. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17beta-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin alpha5beta1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin alpha5beta1 complexes. Function-blocking antibodies directed against integrin alpha5beta1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin beta1-deficient GE11 cells, whereas reintroduction of integrin beta1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin alpha5beta1 complexes, yet this mutant did not prevent endogenous Shc-integrin alpha5beta1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin alpha5beta1.

  1. Could tight junctions regulate the barrier function of the aged skin?

    PubMed

    Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš

    2016-03-01

    The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. DNA methylation down-regulates EGFR expression in chicken

    USDA-ARS?s Scientific Manuscript database

    The epidermal growth factor receptor (EGFR), a growth-factor-receptor tyrosine kinase, was found up-regulated in numerous tumors, which provides a good target for cancer therapy. Although it was documented that oncoviruses are responsible for the activation of EGFR in tumors, the impact of Marek’s d...

  3. Occlusal Enamel Complexity in Middle Miocene to Holocene Equids (Equidae: Perissodactyla) of North America

    PubMed Central

    Famoso, Nicholas A.; Davis, Edward Byrd

    2014-01-01

    Four groups of equids, “Anchitheriinae,” Merychippine-grade Equinae, Hipparionini, and Equini, coexisted in the middle Miocene, but only the Equini remains after 16 Myr of evolution and extinction. Each group is distinct in its occlusal enamel pattern. These patterns have been compared qualitatively but rarely quantitatively. The processes influencing the evolution of these occlusal patterns have not been thoroughly investigated with respect to phylogeny, tooth position, and climate through geologic time. We investigated Occlusal Enamel Index, a quantitative method for the analysis of the complexity of occlusal patterns. We used analyses of variance and an analysis of co-variance to test whether equid teeth increase resistive cutting area for food processing during mastication, as expressed in occlusal enamel complexity, in response to increased abrasion in their diet. Results suggest that occlusal enamel complexity was influenced by climate, phylogeny, and tooth position through time. Occlusal enamel complexity in middle Miocene to Modern horses increased as the animals experienced increased tooth abrasion and a cooling climate. PMID:24587267

  4. Evaluation of recovery in lip closing pressure and occlusal force and contact area after orthognathic surgery.

    PubMed

    Ueki, Koichiro; Moroi, Akinori; Sotobori, Megumi; Ishihara, Yuri; Marukawa, Kohei; Iguchi, Ran; Kosaka, Akihiko; Ikawa, Hiroumi; Nakazawa, Ryuichi; Higuchi, Masatoshi

    2014-10-01

    The purpose of this study was to evaluate the relationship between lip closing force, occlusal contact area and occlusal force after orthognathic surgery in skeletal Class III patients. The subjects consisted of 54 patients (28 female and 26 male) diagnosed with mandibular prognathism who underwent sagittal split ramus osteotomy with and without Le Fort I osteotomy. Maximum and minimum lip closing forces, occlusal contact area and occlusal force were measured pre-operatively, 6 months and 1 year post-operative. Maximum and minimum lip closing forces, occlusal contact area and occlusal force increased with time after surgery, however a significant increase was not found in the occlusal contact area in women. In increased ratio (6 months/pre-operative and 1 year/pre-operative), the maximum lip closing force was significantly correlated with the occlusal contact area (P < 0.0001). This study suggested that orthognathic surgery could improve the occlusal force, contact area and lip closing force, and an increase ratio in maximum lip closing force was associated with an increased ratio in occlusal contact area. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  5. Morphological and functional studies on the epidermal cells of amphioxus ( Branchiostoma belcheri tsingtauense) at different developmental stages

    NASA Astrophysics Data System (ADS)

    Mao, Bing-Yu; Sun, Xiao-Yang; Zhang, Hong-Wei; Zhang, Shi-Cui; Wu, Xian-Han

    1997-09-01

    Epidermal cells of amphioxus at different developmental stages were investigated by electron microscopy and colloidal carbon tracing experiments. Amphioxus epidermal cells showed different ultrastructural characteristics at larval and adult stages. The epidermal cells at all larval stages studied (24 96 h) had numerous vesicles containing electron dense materials in their apical cytoplasm. In tracing experiments, carbon particles were found in apical vesicles and interoellular spaces. Under scanning electron microscope, many crater-like protrusions were observed on the surface of the cells. These results indicated that amphioxus larval epidermal cells may be capable of endocytosis. The epidermal cells of 3-month and adult amphioxus were obviously secretory ones characterized by well-developed peripheral filaments, a prominent Golgi apparatus and abundant apical secretory vesicles. This study also showed that adult amphioxus body surface mucus contained lectin that could agglutinate human red blood cells. The authors propose that the epidermal cells of amphioxus larva and adult may contribute to the immune defense of the amimal by different means.

  6. Reversal of myopic anisometropic amblyopia with occlusion therapy in a 25 year old.

    PubMed

    Megbelayin, E; Ekpenyong, S M; Azunobi, J; Ejiro, G

    2014-03-01

    To report a reversal of myopic anisometropic amblyopia with occlusion therapy in a 25 year old. Case report. Eye clinic of a University Teaching Hospital in a metropolitan city. an index patient. Occlusion therapy. Post occlusion visual acuity. Presenting unaided visual acuity of right eye: 6/6, left eye: 4/60. Refraction result was: right eye: -0.50DS (6/6), left eye: -3.50DS (6/18). Following day time occlusion therapy of at least 6 hours for about 4 weeks, subjective refraction was: right eye: -0.5DS (6/5), left eye: -3.50DS (6/6(+3)). The remarkable improvement in vision at age 25 years of a patient with myopic anisometropic amblyopia shows that occlusion therapy might still be useful long after amblyogenic period.

  7. Veno-occlusive disease and primary hepatic vein thrombosis in Israeli Arabs.

    PubMed

    Ghanem, J; Hershko, C

    1981-05-01

    In a survey of nine major Israeli hospitals, 29 patients diagnosed between 1955 and 1975 as suffering from hepatic vein thrombosis were identified. Fifteen of the patients were Jews and 14 were Arabs. In contrast to the Jewish patients, all of whom were adults, the majority of the Arab patients were children below 10 years of age. Primary hepatic vein occlusion was 2.4 times more common among Arab than among Jewish patients. Of the 11 Arab patients with primary hepatic vein occlusion, three had histological changes typical of veno-occlusive disease; whereas in five others, thrombotic occlusion of large hepatic veins or of the vena cava was documented. Although no plant alkaloids could be directly implicated in any of the Arab patients, circumstantial evidence strongly supports such an etiology. All of our Arab patients originated from small agricultural communities where ancient methods of winnowing, which expose the home-ground wheat to a high risk of contamination by grains containing pyrrolizidine alkaloids, are still in use. This report confirms the world-wide distribution of veno-occlusive disease, and under-lines the need for a systematic search for possible sources of poisoning by pyrrolizidine alkaloids.

  8. The effect of occlusion therapy on motion perception deficits in amblyopia.

    PubMed

    Giaschi, Deborah; Chapman, Christine; Meier, Kimberly; Narasimhan, Sathyasri; Regan, David

    2015-09-01

    There is growing evidence for deficits in motion perception in amblyopia, but these are rarely assessed clinically. In this prospective study we examined the effect of occlusion therapy on motion-defined form perception and multiple-object tracking. Participants included children (3-10years old) with unilateral anisometropic and/or strabismic amblyopia who were currently undergoing occlusion therapy and age-matched control children with normal vision. At the start of the study, deficits in motion-defined form perception were present in at least one eye in 69% of the children with amblyopia. These deficits were still present at the end of the study in 55% of the amblyopia group. For multiple-object tracking, deficits were present initially in 64% and finally in 55% of the children with amblyopia, even after completion of occlusion therapy. Many of these deficits persisted in spite of an improvement in amblyopic eye visual acuity in response to occlusion therapy. The prevalence of motion perception deficits in amblyopia as well as their resistance to occlusion therapy, support the need for new approaches to amblyopia treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification.

    PubMed

    Chang, Wing Y; Bryce, Dawn M; D'Souza, Sudhir J A; Dagnino, Lina

    2004-12-03

    The epidermis is a stratified epithelium constantly replenished through the ability of keratinocytes in its basal layer to proliferate and self-renew. The epidermis arises from a single-cell layer ectoderm during embryogenesis. Large proliferative capacity is central to ectodermal cell and basal keratinocyte function. DP-1, a heterodimeric partner of E2F transcription factors, is highly expressed in the ectoderm and all epidermal layers during embryogenesis. To investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A promoter is predominantly bound in proliferating keratinocytes by complexes containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes in organotypic culture and observed that DP-1 inhibition negatively affected stratification of these cells. Likewise, expression of dnDP-1 in embryonic ectoderm explants produced extensive disorganization of subsequently formed epidermal basal and suprabasal layers, interfering with normal epidermal formation. We conclude that DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition.

  10. Choice of biomaterials—Do soft occlusal splints influence jaw-muscle activity during sleep? A preliminary report

    NASA Astrophysics Data System (ADS)

    Arima, Taro; Takeuchi, Tamiyo; Tomonaga, Akio; Yachida, Wataru; Ohata, Noboru; Svensson, Peter

    2012-12-01

    -material occlusal splint does not seem to inhibit jaw-muscle activity during sleep. Within the limitation of the study, it appears that the choice of biomaterials for occlusal splints may have a significant impact on the neurobiological regulation of jaw-muscle activity during sleep.

  11. Guide wire extension for shape memory polymer occlusion removal devices

    DOEpatents

    Maitland, Duncan J [Pleasant Hill, CA; Small, IV, Ward; Hartman, Jonathan [Sacramento, CA

    2009-11-03

    A flexible extension for a shape memory polymer occlusion removal device. A shape memory polymer instrument is transported through a vessel via a catheter. A flexible elongated unit is operatively connected to the distal end of the shape memory polymer instrument to enhance maneuverability through tortuous paths en route to the occlusion.

  12. Computerized classification of proximal occlusion in the left anterior descending coronary artery.

    PubMed

    Gregg, Richard E; Nikus, Kjell C; Zhou, Sophia H; Startt Selvester, Ronald H; Barbara, Victoria

    2010-01-01

    Proximal occlusion within the left anterior descending (LAD) coronary artery in patients with acute myocardial infarction leads to higher mortality than does nonproximal occlusion. We evaluated an automated program to detect proximal LAD occlusion. All patients with suspected acute coronary syndrome (n = 7,710) presenting consecutively to the emergency department of a local hospital with a coronary angiogram–confirmed flow-limiting lesion and notation of occlusion site were included in the study (n = 711). Electrocardiograms (ECGs) that met ST-segment elevation myocardial infarction (STEMI) criteria were included in the training set (n = 183). Paired angiographic location of proximal LAD and ECGs with ST elevation in the anterolateral region were used for the computer program development (n = 36). The test set was based on ECG criteria for anterolateral STEMI only without angiographic reports (n = 162). Tested against 2 expert cardiologists' agreed reading of proximal LAD occlusion, the algorithm has a sensitivity of 95% and a specificity of 82%. The algorithm is designed to have high sensitivity rather than high specificity for the purpose of not missing any proximal LAD in the STEMI population. Our preliminary evaluation suggests that the algorithm can detect proximal LAD occlusion as an additional interpretation to STEMI detection with similar accuracy as cardiologist readers.

  13. Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis

    PubMed Central

    Zilberman, Yuliya; Abrams, Joshua; Anderson, Dorian C.

    2017-01-01

    During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis. PMID:28903999

  14. 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

  15. Retinal vein occlusion: current treatment.

    PubMed

    Lattanzio, Rosangela; Torres Gimeno, Ana; Battaglia Parodi, Maurizio; Bandello, Francesco

    2011-01-01

    Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management. Copyright © 2010 S. Karger AG, Basel.

  16. The impact of occlusal plane cant along with gingival display on smile attractiveness.

    PubMed

    Kaya, B; Uyar, R

    2016-05-01

    To evaluate the influence of occlusal plane cant in conjunction with maxillary gingival display on perception of smile attractiveness by orthodontists, dentists, and laypersons. Faculty of Dentistry at Baskent University. A total of 204 raters for smile attractiveness. A frontal intra-oral photograph of aligned teeth was modified using image processing software. Six different occlusal lines representing 0° to 5° cants were obtained by tilting the photographs. Each occlusal cant was adjusted in five manners resulting in five different gingival display amounts. Attractiveness of the 30 different smiles was evaluated by 204 raters divided into three groups (n = 68 in each group). Both occlusal cant (p < 0.001) and gingival display amount (p < 0.001) had a statistically significant influence on smile attractiveness. Smile attractiveness scores with reference to amount of gingival display showed a significant difference between rater groups (p < 0.001). Orthodontists preferred 1-mm coverage of upper central incisors by the upper lip, whereas dentists and laypersons preferred 2 mm. Significant (p < 0.001) interaction was observed between occlusal cant and gingival display amount, which influenced smile attractiveness. Increase in both occlusal plane cant and gingival display negatively influences smile attractiveness. The influence of occlusal plane cant becomes less when gingival display increases, whereas the influence of gingival display decreases when occlusal cant increases. Dentists are more generous than orthodontists, while laypersons are the most generous regarding smile attractiveness scores. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. IL-15 Enhances Activation and IGF-1 Production of Dendritic Epidermal T Cells to Promote Wound Healing in Diabetic Mice.

    PubMed

    Wang, Yangping; Bai, Yang; Li, Yashu; Liang, Guangping; Jiang, Yufeng; Liu, Zhongyang; Liu, Meixi; Hao, Jianlei; Zhang, Xiaorong; Hu, Xiaohong; Chen, Jian; Wang, Rupeng; Yin, Zhinan; Wu, Jun; Luo, Gaoxing; He, Weifeng

    2017-01-01

    Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL-15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and IGF-1 were positively correlated in wounded epidermis. Together, our data indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic wound repair, suggesting IL-15 as a potential therapeutic agent for managing diabetic wound healing.

  18. Real-time three-dimensional imaging of epidermal splitting and removal by high-definition optical coherence tomography.

    PubMed

    Boone, Marc; Draye, Jean Pierre; Verween, Gunther; Pirnay, Jean-Paul; Verbeken, Gilbert; De Vos, Daniel; Rose, Thomas; Jennes, Serge; Jemec, Gregor B E; Del Marmol, Véronique

    2014-10-01

    While real-time 3-D evaluation of human skin constructs is needed, only 2-D non-invasive imaging techniques are available. The aim of this paper is to evaluate the potential of high-definition optical coherence tomography (HD-OCT) for real-time 3-D assessment of the epidermal splitting and decellularization. Human skin samples were incubated with four different agents: Dispase II, NaCl 1 M, sodium dodecyl sulphate (SDS) and Triton X-100. Epidermal splitting, dermo-epidermal junction, acellularity and 3-D architecture of dermal matrices were evaluated by High-definition optical coherence tomography before and after incubation. Real-time 3-D HD-OCT assessment was compared with 2-D en face assessment by reflectance confocal microscopy (RCM). (Immuno) histopathology was used as control. HD-OCT imaging allowed real-time 3-D visualization of the impact of selected agents on epidermal splitting, dermo-epidermal junction, dermal architecture, vascular spaces and cellularity. RCM has a better resolution (1 μm) than HD-OCT (3 μm), permitting differentiation of different collagen fibres, but HD-OCT imaging has deeper penetration (570 μm) than RCM imaging (200 μm). Dispase II and NaCl treatments were found to be equally efficient in the removal of the epidermis from human split-thickness skin allografts. However, a different epidermal splitting level at the dermo-epidermal junction could be observed and confirmed by immunolabelling of collagen type IV and type VII. Epidermal splitting occurred at the level of the lamina densa with dispase II and above the lamina densa (in the lamina lucida) with NaCl. The 3-D architecture of dermal papillae and dermis was more affected by Dispase II on HD-OCT which corresponded with histopathologic (orcein staining) fragmentation of elastic fibres. With SDS treatment, the epidermal removal was incomplete as remnants of the epidermal basal cell layer remained attached to the basement membrane on the dermis. With Triton X-100 treatment

  19. [Integrated therapeutic strategy in large bowel neoplastic occlusion. An innovative therapeutic protocol].

    PubMed

    Gattai, Riccardo; Mascitelli, Erminia Macera; Bechi, Paolo; Pace, Marcello

    2007-01-01

    Occlusive complication is a common event in the colo-rectal cancer (20-30% of cases). Operative mortality and 5 yrs survival of not occlusive cancer vs occlusive cancer is 11% vs 23% and 45% vs 25% rispectively. In occlusive cancer the level of parietal infiltration affects considerably the local and peritoneal recurrence. 50% of all patients underwent a surgical re-operation for colo-rectal cancer have peritoneal neoplastic implant. The resolution of occlusive complication in immediate or delayed urgency with decompressive derivation, it allows to perform an integrated treatment of choice that it could guarantee the oncological radical procedure. RATIONALE-METHODS: The intraperitoneal hyperthermic chemotherapy (IPHC) combined with radical or cytoriductive surgery performs its action through sinergistic effects of high dosage and concentration of drugs and hyperthermia. These agents perform a cell killing with a direct contact against micro and/or macroscopic neoplastic residue. In radical surgery with curative intent, the association with IPHC ("preventive" adjuvant) has got as objective the distruction of microscopic local or peritoneal metastasis. In occlusive cancer with synchronous or metachronous peritoneal carcinomatosis, the performance of the cytoreductive surgery with IPHC ("therapeutic" adjuvant) is the only treatment that improves the survival and the quality of remainig life. The clinical results reported by many Istitutions indicates that the 2-5 yrs survivals are 45-60% and 20-30% rispectively. These data lead us to believe that an optimal eradication of micro and/or macroscopic peritoneal spreading could be optained also in occlusive colo-rectal cancer.

  20. Comparison of occlusion break responses and vacuum rise times of phacoemulsification systems

    PubMed Central

    2014-01-01

    Background Occlusion break surge during phacoemulsification cataract surgery can lead to potential surgical complications. The purpose of this study was to quantify occlusion break surge and vacuum rise time of current phacoemulsification systems used in cataract surgery. Methods Occlusion break surge at vacuum pressures between 200 and 600 mmHg was assessed with the Infiniti® Vision System, the WhiteStar Signature® Phacoemulsification System, and the Centurion® Vision System using gravity-fed fluidics. Centurion Active FluidicsTM were also tested at multiple intraoperative pressure target settings. Vacuum rise time was evaluated for Infiniti, WhiteStar Signature, Centurion, and Stellaris® Vision Enhancement systems. Rise time to vacuum limits of 400 and 600 mmHg was assessed at flow rates of 30 and 60 cc/minute. Occlusion break surge was analyzed by 2-way analysis of variance. Results The Centurion system exhibited substantially less occlusion break surge than the other systems tested. Surge area with Centurion Active Fluidics was similar to gravity fluidics at an equivalent bottle height. At all Centurion Active Fluidics intraoperative pressure target settings tested, surge was smaller than with Infiniti and WhiteStar Signature. Infiniti had the fastest vacuum rise time and Stellaris had the slowest. No system tested reached the 600-mmHg vacuum limit. Conclusions In this laboratory study, Centurion had the least occlusion break surge and similar vacuum rise times compared with the other systems tested. Reducing occlusion break surge may increase safety of phacoemulsification cataract surgery. PMID:25074069

  1. Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes.

    PubMed

    Choi, Mi-Ra; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lim, Seul Ki; Kim, Dong-Il; Lee, Young Ho; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

    2015-01-01

    Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1β and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis.

  2. Protein profiling of single epidermal cell types from Arabidopsis thaliana using surface-enhanced laser desorption and ionization technology.

    PubMed

    Ebert, Berit; Melle, Christian; Lieckfeldt, Elke; Zöller, Daniela; von Eggeling, Ferdinand; Fisahn, Joachim

    2008-08-25

    Here, we describe a novel approach for investigating differential protein expression within three epidermal cell types. In particular, 3000 single pavement, basal, and trichome cells from leaves of Arabidopsis thaliana were harvested by glass micro-capillaries. Subsequently, these single cell samples were joined to form pools of 100 individual cells and analyzed using the ProteinChip technology; SELDI: surface-enhanced laser desorption and ionization. As a result, numerous protein signals that were differentially expressed in the three epidermal cell types could be detected. One of these proteins was characterized by tryptical digestion and subsequent identification via tandem quadrupole-time of flight (Q-TOF) mass spectrometry. Down regulation of this sequenced small subunit precursor of ribulose-1,5 bisphosphate carboxylase(C) oxygenase(O) (RuBisCo) in trichome and basal cells indicates the sink status of these cell types that are located on the surface of A. thaliana source leaves. Based on the obtained protein profiles, we suggest a close functional relationship between basal and trichome cells at the protein level.

  3. Regenerative and reparative effects of human chorion-derived stem cell conditioned medium on photo-aged epidermal cells

    PubMed Central

    Li, Qiankun; Chen, Yan; Ma, Kui; Zhao, Along; Zhang, Cuiping; Fu, Xiaobing

    2016-01-01

    ABSTRACT Epidermal cells are an important regenerative source for skin wound healing. Aged epidermal cells have a low ability to renew themselves and repair skin injury. Ultraviolet (UV) radiation, particularly UVB, can cause photo-aging of the skin by suppressing the viability of human epidermal cells. A chorion-derived stem cell conditioned medium (CDSC-CNM) is thought to have regenerative properties. This study aimed to determine the regenerative effects of CDSC-CNM on UVB-induced photo-aged epidermal cells. Epidermal cells were passaged four times and irradiated with quantitative UVB, and non-irradiated cells served as a control group. Cells were then treated with different concentrations of CDSC-CNM. Compared to the non-irradiated group, the proliferation rates and migration rates of UVB-induced photo-aged epidermal cells significantly decreased (p < 0.05) with increasing intracellular radical oxygen species (ROS) generation and DNA damage. After treatment with CDSC-CNM, photo-aged epidermal cells significantly improved their viability, and their ROS generation and DNA damage decreased. The secretory factors in CDSC-CNM, including epidermal growth factor (EGF), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-8 and the related signaling pathway protein levels, increased compared to the control medium (CM). The potential regenerative and reparative effects of CDSC-CNM indicate that it may be a candidate material for the treatment of prematurely aged skin. The functions of the secretory factors and the mechanisms of CDSC-CNM therapy deserve further attention. PMID:27097375

  4. Ventilation Increases with Lower Extremity Venous Occlusion in Young Adults

    PubMed Central

    Keller-Ross, Manda L.; Cowl, Andrielle L.; Cross, Troy; Johnson, Bruce D.; Olson, Thomas P.

    2015-01-01

    Introduction Venous distention via sub-systolic occlusion of the lower limbs may augment ventilation via stimulation of group III/IV afferent neurons. Purpose The purpose of this study was to examine the ventilatory response to graded lower extremity venous occlusion during exercise in healthy adults. Methods Nineteen adults (9 men, 25±5 yr) completed two visits. Visit 1: a maximal cycle ergometry exercise test. Visit 2 included a 30% peak workload cycle exercise with randomized inflations of bilateral thigh pressure tourniquets to 20, 40, 60, 80, 100 mmHg for 2 min each, separated by 2 min of deflation. Three min of cycling occurred prior to cuffing (CTL). Expired minute ventilation (VE), whole body gas exchange, rating of perceived exertion and dyspnea were measured during each session. Results VE increased significantly from the control condition (exercise only, control, CTL) to each occlusion pressure (p<0.05) with the greatest increase at 100 mmHg (CTL to 100 mmHg: 31.5±6.6 to 40.1±10.7 L/min). Respiratory rate (RR) increased as well (CTL to 100 mmHg: 24.8±6.0 to 30.9±11.5 breaths/min, p<0.05, condition effect) with no change in tidal volume (p>0.05). Tidal volume to inspiratory time (VT/TI) increased significantly from the CTL condition to each occlusion pressure (CTL to 100 mmHg: 1.5±0.3 to 1.8±0.4 L/min, p<0.05, all pressures). Dyspnea and RPE increased with all occlusion pressures from CTL exercise (p<0.05, all pressures). Conclusion Our findings suggest that mild-to-moderate venous occlusion of the lower extremity evokes a tachypneic breathing pattern which, in turn, augments VE and perceived breathing effort during exercise. PMID:26484951

  5. Neural substrates of dynamic object occlusion.

    PubMed

    Shuwairi, Sarah M; Curtis, Clayton E; Johnson, Scott P

    2007-08-01

    In everyday environments, objects frequently go out of sight as they move and our view of them becomes obstructed by nearer objects, yet we perceive these objects as continuous and enduring entities. Here, we used functional magnetic resonance imaging with an attentive tracking paradigm to clarify the nature of perceptual and cognitive mechanisms subserving this ability to fill in the gaps in perception of dynamic object occlusion. Imaging data revealed distinct regions of cortex showing increased activity during periods of occlusion relative to full visibility. These regions may support active maintenance of a representation of the target's spatiotemporal properties ensuring that the object is perceived as a persisting entity when occluded. Our findings may shed light on the neural substrates involved in object tracking that give rise to the phenomenon of object permanence.

  6. Mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors sensitize reduced glucocorticoid response mediated by TNF{alpha} in human epidermal keratinocytes (HaCaT)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Onda, Kenji; Nagashima, Masahiro; Kawakubo, Yo

    2006-12-08

    Glucocorticoids (GCs) are essential drugs administered topically or systematically for the treatment of autoimmune skin diseases such as pemphigus. However, a certain proportion of patients does not respond well to GCs. Although studies on the relationship between cytokines and GC insensitivity in local tissues have attracted attention recently, little is known about the underlying mechanism(s) for GC insensitivity in epidermal keratinocytes. Here, we report that tumor necrosis factor (TNF) {alpha} reduces GC-induced transactivation of endogenous genes as well as a reporter plasmid which contains GC responsive element (GRE) in human epidermal keratinocyte cells (HaCaT). The GC insensitivity by TNF{alpha} wasmore » not accompanied by changes in mRNA expressions of GR isoforms ({alpha} or {beta}). However, we observed that mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors (PD98059 and U0126) significantly sensitized the GC-induced transactivation of anti-inflammatory genes (glucocorticoid-induced leucine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP)-1) and FK506 binding protein (FKBP) 51 gene in the presence of TNF{alpha}. Additionally, we observed that TNF{alpha} reduced prednisolone (PSL)-dependent nuclear translocation of GR, which was restored by pre-treatment of MEK-1 inhibitors. This is the first study demonstrating a role of the MEK-1/ERK cascade in TNF{alpha}-mediated GC insensitivity. Our data suggest that overexpression of TNF{alpha} leads to topical GC insensitivity by reducing GR nuclear translocation in keratinocytes, and our findings also suggest that inhibiting the MEK-1/ERK cascade may offer a therapeutic potential for increasing GC efficacy in epidermis where sufficient inflammatory suppression is required.« less

  7. Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia.

    PubMed

    Derenne, J P; Couture, J; Iscoe, S; Whitelaw, A; Milic-Emili, J

    1976-05-01

    The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.

  8. 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.

  9. [Epidermal cyst and osteolysis of the cranial vault].

    PubMed

    Guillaud, V; Rémond, J; Balme, B; Moulin, G

    1992-01-01

    In a 40-year old man undergoing, under local anaesthesia, excision of an epidermal cyst located in the frontal region, at the border of the scalp, the operator had difficulties in removing the deep part of the cyst and perceived an underlying bone depression. The depression was caused by a 2 x 1.3 cm wide lacuna in the calvarium, which was subsequently treated by neurosurgeons. Histology showed only fragments of a simple epidermal cyst wall and no evidence of dermoid cyst. The causes of osteolysis associated with congenital or acquired skin lesions are reviewed. In this case, the old age and volume of the cyst may explain the osteolysis by mechanical compression. This case is exceptional since we were unable to find other examples in the literature, apart from dermoid and trichilemmal cysts.

  10. [A cephalometric study on determining the orientation of occlusal plane].

    PubMed

    Xie, J; Zhao, Y; Chao, Y; Luo, W

    1993-12-01

    A study of the parallel relationship between the occlusal plane and the line connecting nasal alar and tragus was made in 90 dentulous cases by using cephalometry. The results show that the line connecting the inferior point of nasal alar and the mid-point of tragus runs much more parallel with the occlusal plane. The regression equation reveals a "line of closest fitting". It was used in the prosthetic treatment for 50 edentulous patients with good clinical results. The line connecting the inferior point of nasal alar and the mid-point of tragus therefore represents a proper reference plane for determining occlusal plane and hence should be still a valuable index in clinical dentistry.

  11. A Novel Nitinol Spherical Occlusion Device for Liver Cancer

    PubMed Central

    Hsiao, Hao-Ming; Wang, Yi-Ping; Ko, Chun-Yi; Cheng, Yu-Han; Lee, Han-Yu

    2016-01-01

    Liver cancer or hepatic cancer is a cancer that originates in the liver. It is formed from either the liver itself or from structures within the liver, including blood vessels or the bile duct. Liver cancer can be a life-threatening condition, but it may be cured if found early. Hepatic artery embolization is one of the treatment options involving the injection of substances to reduce the blood flow to cancer cells in the livers of patients with tumors that cannot be removed by surgery; however, this treatment has some limitations. In this paper, we propose a novel nitinol “spherical occlusion device” concept, the first of its kind in the world. Our proposed spherical occlusion device is able to reduce the blood flow to cancer cells by deploying it in the upstream hepatic artery supplying blood to the liver. Moreover, it could carry multiple chemotherapy or radioactive drugs for delivery directly to the target site. Nitinol alloy was chosen as the device material due to its excellent super-elastic property. Computational models were developed to predict the mechanical response of the device during manufacturing and deployment procedures, as well as its hemodynamic behavior. Simulation results showed that the presence of the spherical occlusion device with 14%–27% metal density deployed at the upstream location of the right hepatic artery had significant occlusion effects, with the average blood flow rate cut down by 30%–50%. A pulsed fiber laser and a series of expansions and heat treatments were developed to make the first prototype of the spherical occlusion device for the demonstration of our novel concept. PMID:28787820

  12. Incidence and Determinants of Port Occlusions in Cancer Outpatients: A Prospective Cohort Study.

    PubMed

    Milani, Alessandra; Mazzocco, Ketti; Gandini, Sara; Pravettoni, Gabriella; Libutti, Livio; Zencovich, Claudia; Sbriglia, Ada; Pari, Chiara; Magon, Giorgio; Saiani, Luisa

    Normal saline is considered a safe alternative for heparin as a locking solution in totally implantable venous access devices. The incidence rate of partial occlusion with the use of normal saline (easy injection, impossible aspiration) is estimated at 4%. The aim of this study was to investigate determinants of partial occlusions with the use of normal saline solution and the maintenance of positive pressure in the catheter. We enrolled 218 patients with different solid tumors who underwent pharmacologic treatment through the port with different frequencies: from once every week to at least once every month. The port was flushed with normal saline solution keeping a positive pressure in the catheter. We performed 4111 observations and documented normal port functioning in 99% of observations (n = 4057) and partial occlusions in 1% of observations (n = 54). Partial occlusions were significantly associated with frequency of port flushing (P < .05), chemotherapy (P < .001), and blood sample collection (P < .001). The use of positive pressure in addition to normal saline reduces the incidence rate of partial occlusions. The type of treatment, blood sample collection, and treatment schedule are important determinants of partial occlusions. Nurses play a key role in maintaining a functioning port using positive pressure during the flushing techniques. Certain risk factors must be monitored to prevent partial occlusions, and certain patients are more likely to present with port-related problems.

  13. Liver size, bodyweight, and tolerance to acute complete occlusion of congenital extrahepatic portosystemic shunts in dogs.

    PubMed

    Doran, Ivan P; Barr, Frances J; Hotston Moore, Alasdair; Knowles, Toby G; Holt, Peter E

    2008-10-01

    To investigate the relationship between preoperative liver size, bodyweight, and tolerance to shunt occlusion in dogs with congenital extrahepatic portosystemic shunt(s) (CPSS). Longitudinal cohort study. Dogs with CPSS (n=35). Ultrasonography was used to measure preoperative maximum transverse dimension of the liver (TS) of each dog. Intraoperative portal pressures were measured, before and after CPSS occlusion, via a jejunal vein catheter. Tolerance to shunt occlusion was judged on gross visceral observations, and on changes in portal pressure, central venous and mean arterial pressures. TS was significantly related to bodyweight (P<.05). Mean ratios for TS/bodyweight were calculated for dogs tolerant and intolerant of acute complete shunt occlusion. Dogs tolerant to occlusion had significantly higher TS/bodyweight ratios than dogs intolerant to occlusion (P=.025). Dogs with a TS/bodyweight ratio of >7 were more likely to tolerate CPSS occlusion than dogs with a TS/bodyweight ratio of <5 (P=.036). A model was generated to predict portal pressure rise after shunt occlusion, based on liver dimensions and bodyweight (R=0.668). Intestinal oxygenation did not correlate significantly with tolerance to CPSS occlusion (P=.29). In dogs with CPSS, liver size (relative to bodyweight) is significantly greater (P=.025) in dogs that are tolerant of full ligation than intolerant of occlusion. Preoperative measurement of bodyweight and liver size help indicate the likelihood of tolerance to acute complete occlusion of CPSS in dogs.

  14. Hybrid Enhanced Epidermal SpaceSuit Design Approaches

    NASA Astrophysics Data System (ADS)

    Jessup, Joseph M.

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

  15. Grhl3 and Lmo4 play coordinate roles in epidermal migration.

    PubMed

    Hislop, Nikki R; Caddy, Jacinta; Ting, Stephen B; Auden, Alana; Vasudevan, Sumitha; King, Sarah L; Lindeman, Geoffrey J; Visvader, Jane E; Cunningham, John M; Jane, Stephen M

    2008-09-01

    In addition to its role in formation of the epidermal barrier, the mammalian transcription factor Grainy head-like 3 (Grhl3) is also essential for neural tube closure and wound repair, processes that are dependent in part on epidermal migration. Here, we demonstrate that the LIM-only domain protein, LMO4 serves as a functional partner of GRHL3 in its established roles, and define a new cooperative role for these factors in another developmental epidermal migration event, eyelid fusion. GRHL3 and LMO4 interact biochemically and genetically, with mutant mice exhibiting fully penetrant exencephaly, thoraco-lumbo-sacral spina bifida, defective skin barrier formation, and a co-incident eyes-open-at-birth (EOB) phenotype, which is not observed in the original individual null lines. The two genes are co-expressed in the surface ectoderm of the migrating eyelid root, and electron microscopy of Grhl3/Lmo4-null eyes reveals a failure in epithelial extension and a lack of peridermal clump formation at the eyelid margins. Accumulation of actin fibers is also absent in the circumference of these eyelids, and ERK1/2 phosphorylation is lost in the epidermis and eyelids of Grhl3(-/-)/Lmo4(-/-) embryos. Keratinocytes from mutant mice fail to "heal" in in vitro scratch assays, consistent with a general epidermal migratory defect that is dependent on ERK activation and actin cable formation.

  16. Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.

    PubMed

    Hu, Lizhi; Mauro, Theodora M; Dang, Erle; Man, George; Zhang, Jing; Lee, Dale; Wang, Gang; Feingold, Kenneth R; Elias, Peter M; Man, Mao-Qiang

    2017-06-01

    Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Occlusal plane rotation: aesthetic enhancement in mandibular micrognathia.

    PubMed

    Rosen, H M

    1993-06-01

    Patients afflicted with extreme degrees of mandibular micrognathia typically have vertically deficient rami as well as sagittally deficient mandibular bodies. This results in deficient posterior facial height, an obtuse gonial angle, excessively steep occlusal and mandibular planes, and a compensatory increase in anterior facial height. The entire maxillomandibular complex is overrotated in a clockwise direction. Standard orthognathic surgical correction fails to address this rotational deformity. As a consequence, the achieved projection of the lower face is inadequate, posterior facial height is further reduced, and occlusal and mandibular planes remain steep. Eleven patients with severe mandibular micrognathia underwent a surgical correction involving occlusal plane rotation to its normal orientation relative to Frankfort horizontal. This was accomplished by Le Fort I osteotomy to shorten the anterior maxilla (creating open bites in seven patients and making preexisting open bites worse in four patients) and sagittal split ramus osteotomies to advance and rotate the mandibular body counterclockwise, thus closing the surgically produced open bite. Counterclockwise rotation of the mandible afforded significantly greater sagittal displacement at the B point (mean 17 mm) than at the first molar (mean 10 mm) and produced adequate degrees of projection of the lower face when accompanied by a modest sliding genioplasty (mean 6.9 mm). Total advancement at the pogonion was a mean of 25.2 mm. In addition, posterior facial height was preserved, and mandibular and occlusal planes were normalized to mean angles of 27 and 10 degrees, respectively. At follow-up, which ranged from 9 to 24 months with a mean of 14.1 months, the mean sagittal relapse at the B point was 1.9 mm. Although heretofore considered unstable and therefore not clinically accepted, maxillomandibular counterclockwise rotation to normalize the occlusal plane rotational deformity provides stable, aesthetically

  18. The peripheral clock regulates human pigmentation.

    PubMed

    Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

    2015-04-01

    Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies.

  19. Amplatzer vascular plug for arteriovenous hemodialysis access occlusion: initial experience.

    PubMed

    Bui, J T; Gaba, R C; Knuttinen, M G; West, D L; Owens, C A

    2009-01-01

    The Amplatzer Vascular Plug (AVP; AGA Medical, Golden Valley, MN) is a recently developed self-expanding metallic device indicated for peripheral vascular embolizations. Herein, we describe use of this device in the treatment of vascular complications related to arteriovenous hemodialysis fistulas and grafts. This HIPAA compliant retrospective study was approved by the institutional review board with informed consent waived. Six patients with problematic arteriovenous access underwent access occlusion using the AVP. Procedure indications included vascular steal syndrome in five patients, and enlarging vascular aneurysms in one patient. Contraindications for surgical correction were determined by the referring surgeon. AVP embolizations were performed using devices oversized by 50% introduced through vascular sheaths positioned within vein segments just beyond the arteriovenous anastomoses. Noninvasive evaluation of the involved extremity was performed pre- and post-embolization in addition to clinical follow-up examinations. Measured outcomes included success of angiographic occlusion, improvement in distal arterial flow, AVP number, AVP diameter, time to access occlusion, and clinical symptomatic improvement. Technical success was 100%, with complete arteriovenous access occlusion accomplished in all cases, with an average of 1.5 AVPs used per patient. Mean time to access occlusion was 19.3 minutes. Angiographic improvement in distal arterial flow was immediately evident and resolution of clinical symptoms occurred in all patients, with mean long-term follow-up of 16 months. No procedure-related complications were encountered. The Amplatzer Vascular Plug provides a minimally invasive and efficacious method for embolization of problematic arteriovenous hemodialysis access.

  20. Patching compliance with full-time vs. part-time occlusion therapy.

    PubMed

    Kane, Jessica; Biernacki, Ron; Fraine, Lisa; Fukuda, Neva; Haskins, Kelsie; Morrison, David G

    2013-01-01

    Amblyopia is commonly treated with part-time occlusion (PTO) therapy. We have made two anecdotal observations regarding this therapy. First, children undergoing full-time occlusion seem to have better success and compliance rates. Secondly, a subset of children exists that fail PTO but can improve with more aggressive therapy. A retrospective review where treatment, visual outcome, and compliance scores were recorded. Compliance was graded on percent adherence reported by family. Patients scored “1” (for no compliance), “2” (for 1–25% of prescribed treatment performed), “3” (for 26–50%), “4” (for 51–75%), or “5” (for 76–100%). Seventy-six children were enrolled in the study: forty-five were treated with part-time occlusion, twenty-two were treated with full time occlusion (FTO), and nine had a history of failed PTO and were subsequently treated with FTO. Visual outcomes for FTO versus PTO were not statistically significant (P = 0.82). However, compliance rates in FTO were significantly better (P = 0.02). Of the nine patients that failed PTO, four improved an average of three lines with full-time occlusion, and five had no change with more aggressive patching. This study confirms previous reports of similar visual outcomes between PTO and FTO. However, compliance rates for FTO seem to be higher and some children who have failed PTO may improve with FTO.

  1. In vivo THz imaging of human skin: Accounting for occlusion effects.

    PubMed

    Sun, Qiushuo; Parrott, Edward P J; He, Yuezhi; Pickwell-MacPherson, Emma

    2018-02-01

    In vivo terahertz (THz) imaging of human skin needs to be done in reflection geometry due to the high attenuation of THz light by water in the skin. To aid the measurement procedure, there is typically an imaging window onto which the patient places the area of interest. The window enables better pulse alignment and helps keep the patient correctly positioned during the measurement. In this paper, we demonstrate how the occlusion caused by the skin contact with the imaging window during the measurement affects the THz response. By studying both rapid point measurements and imaging over an area of a human volar forearm, we find that even 5 seconds of occlusion affects the THz response. As the occlusion time increases, the skin surface water content increases, resulting in the reduction of the amplitude of the reflected THz pulse, especially in the first 3 minutes. Furthermore, it was found that the refractive index of the volar forearm increased by 10% to 15% after 20 minutes of occlusion. In this work, we examine and propose a model for the occlusion effects due to the quartz window with a view to compensating for its influence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Temporary Arterial Balloon Occlusion as an Adjunct to Yttrium-90 Radioembolization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hagspiel, Klaus D., E-mail: kdh2n@virginia.edu; Nambiar, Ashwin, E-mail: uvashwin@gmail.com; Hagspiel, Lauren M., E-mail: lmh4gg@virginia.edu

    2013-06-15

    Purpose. This study was designed to describe the technique of arterial occlusion using a temporary occlusion balloon system as an alternative to coil occlusion during Yttrium-90 radioembolization of hepatic tumors. Methods. Review of charts, angiography, and follow-up imaging studies of consecutive patients undergoing oncological embolization procedures in which a HyperForm system (ev3 Neurovascular, Irvine, CA) was used. Intraprocedural target vessel occlusion and patency of the target vessel on follow-up were recorded. Clinical data and Bremsstrahlung scans were reviewed for evidence of nontarget embolization. Results. Four radioembolization procedures were performed in three patients (all female, age 48-54 (mean 52) years). Fivemore » arteries were temporarily occluded (three gastroduodenal arteries, one right gastric artery, and one cystic artery). All radioembolization procedures were successfully completed. Follow-up imaging (either digital subtraction angiography (DSA) or computed tomography angiography (CTA)) was available for all patients between 28-454 (mean 183) days following the procedure, demonstrating all five vessels to be patent. No clinical or imaging evidence for nontarget embolization was found. Conclusions. Temporary balloon occlusion of small and medium-sized arteries during radioembolization allows safe therapy with preserved postprocedural vessel patency on early and midterm follow-up.« less

  3. Evaluation of in-vehicle HMI using occlusion techniques: experimental results and practical implications.

    PubMed

    Baumann, Martin; Keinath, Andreas; Krems, Josef F; Bengler, Klaus

    2004-05-01

    Despite the usefulness of new on-board information systems one has to be concerned about the potential distraction effects that they impose on the driver. Therefore, methods and procedures are necessary to assess the visual demand that is connected to the usage of an on-board system. The occlusion-method is considered a strong candidate as a procedure for evaluating display designs with regard to their visual demand. This paper reports results from two experimental studies conducted to further evaluate this method. In the first study, performance in using an in-car navigation system was measured under three conditions: static (parking lot), occlusion (shutter glasses), and driving. The results show that the occlusion-procedure can be used to simulate visual requirements of real traffic conditions. In a second study the occlusion method was compared to a global evaluation criterion based on the total task time. It can be demonstrated that the occlusion method can identify tasks which meet this criterion, but are yet irresolvable under driving conditions. It is concluded that the occlusion technique seems to be a reliable and valid method for evaluating visual and dialogue aspects of in-car information systems.

  4. Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion

    PubMed Central

    Zhou, Minglong; Widmer, R. Jay; Xie, Wei; Jimmy Widmer, A.; Miller, Matthew W.; Schroeder, Friedhelm; Parker, Janet L.

    2010-01-01

    Exercise training enhances agonist-mediated relaxation in both control and collateral-dependent coronary arteries of hearts subjected to chronic occlusion, an enhancement that is mediated in part by nitric oxide. The purpose of the present study was to elucidate exercise training-induced adaptations in specific cellular mechanisms involved in the regulation of endothelial nitric oxide synthase (eNOS) in coronary arteries of ischemic hearts. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniature swine. Eight weeks postoperatively, animals were randomized into sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) protocols. Coronary artery segments (∼1.0 mm luminal diameter) were isolated from collateral-dependent (LCX) and control (nonoccluded left anterior descending) arteries 22 wk after ameroid placement. Endothelial cells were enzymatically dissociated, and intracellular Ca2+ responses (fura 2) to bradykinin stimulation were studied. Immunofluorescence and laser scanning confocal microscopy were used to quantify endothelial cell eNOS and caveolin-1 cellular distribution under basal and bradykinin-stimulated conditions. Immunoblot analysis was used to determine eNOS, phosphorylated (p)-eNOS, protein kinase B (Akt), pAkt, and caveolin-1 protein levels. Bradykinin-stimulated nitrite plus nitrate (NOx; nitric oxide metabolites) levels were assessed via HPLC. Exercise training resulted in significantly enhanced bradykinin-mediated increases in endothelial Ca2+ levels, NOx levels, and the distribution of eNOS-to-caveolin-1 ratio at the plasma membrane in endothelial cells of control and collateral-dependent arteries. Exercise training also significantly increased total eNOS and phosphorylated levels of eNOS (pSer1179) in collateral-dependent arteries. Total eNOS protein levels were also significantly increased in collateral-dependent arteries of sedentary

  5. Differences between Subjective Balanced Occlusion and Measurements Reported With T-Scan III

    PubMed Central

    Lila-Krasniqi, Zana; Shala, Kujtim; Krasniqi, Teuta Pustina; Bicaj, Teuta; Ahmedi, Enis; Dula, Linda; Dragusha, Arlinda Tmava; Guguvcevski, Ljuben

    2017-01-01

    BACKGROUND: The aetiology of Temporomandibular disorder is multifactorial, and numerous studies have addressed that occlusion may be of great importance in the pathogenesis of Temporomandibular disorder. AIM: The aim of this study is to determine if any direct relationship exists between balanced occlusion and Temporomandibular disorder and to evaluate the differences between subjective balanced occlusion and measurements reported with T-scan III electronic system. MATERIAL AND METHODS: A total of 54 subjects were divided into three groups, selection based on anamnesis-responded to a Fonseca questionnaire and clinical measurements analysed with electronic system T-scan III. In the I study group were participants with fixed dentures with prosthetic ceramic restorations. In the II study group were symptomatic participants with TMD. In the third control group were healthy participants with full arch dentition that completed a subjective questionnaire that documented the absence of jaw pain, joint noise, locking and subjects without a history of TMD. The occlusal balance was reported subjectively through Fonseca questionnaire and compared with occlusion analysed with electronic system T-scan III. RESULTS: For attributive data were used percentage of the structure. Differences in P < 0.05 were considered significant. After distributing attributive data of occlusal balance subjectively reported and compared with measurements analysed with electronic system T-scan III were found significant difference P < 0.001 in all three groups. CONCLUSION: In our study, it was concluded that there were statistically significant differences of balanced occlusion in all three groups. Also it was concluded that subjective data are not exact with measurements reported with electronic device T-scan III. PMID:28932311

  6. Comparative study to evaluate the accuracy of polyether occlusal bite registration material and occlusal registration wax as a guide for occlusal reduction during tooth preparation.

    PubMed

    Joshi, Niranjan; Shetty, Sridhar N; Prasad, Krishna D

    2013-01-01

    The use of different materials and techniques has been studied to decide the safest quantum of reduction of the occlusal surfaces. However, these methods provide limited information as to the actual amount of reduction with limitations in accuracy, accessibility and complexity. The objective of this study was to compare and evaluate the reliability of the most commonly used occlusal registration wax that with polyether bite registration material as a guide for occlusal reduction required during tooth preparations. For the purpose of this study, 25 abutment teeth requiring tooth preparation for fixed prosthesis were selected and tooth preparations carried out. Modeling wax strips of specific dimensions were placed onto the cast of prepared tooth, which was mounted on maximum intercuspation on the articulator and the articulator was closed. The thickness of the wax registration was measured at three zones namely two functional cusps and central fossa. Similar measurements were made using the polyether bite registration material and prosthesis at the same zones. The data was tabulated and was subjected to statistical analysis using anova test and Tukey honestly significant difference test. The differences in thickness between wax record and prosthesis by 0.1346 mm, whereas the difference between polyether and prosthesis was 0.02 mm with a P value of 0.042, which is statistically significant. This means that the wax record was 8.25% larger than the prosthesis while polyether was just 1.27% larger than the prosthesis. The clinical significance of the above analysis is that Ramitec polyether bite registration material is most suitable material when compared with commonly used modeling wax during the tooth preparation.

  7. Pleiotropic phenotypes of the sticky peel mutant provide new insight into the role of CUTIN DEFICIENT2 in epidermal cell function in tomato.

    PubMed

    Nadakuduti, Satya Swathi; Pollard, Mike; Kosma, Dylan K; Allen, Charles; Ohlrogge, John B; Barry, Cornelius S

    2012-07-01

    Plant epidermal cells have evolved specialist functions associated with adaptation to stress. These include the synthesis and deposition of specialized metabolites such as waxes and cutin together with flavonoids and anthocyanins, which have important roles in providing a barrier to water loss and protection against UV radiation, respectively. Characterization of the sticky peel (pe) mutant of tomato (Solanum lycopersicum) revealed several phenotypes indicative of a defect in epidermal cell function, including reduced anthocyanin accumulation, a lower density of glandular trichomes, and an associated reduction in trichome-derived terpenes. In addition, pe mutant fruit are glossy and peels have increased elasticity due to a severe reduction in cutin biosynthesis and altered wax deposition. Leaves of the pe mutant are also cutin deficient and the epicuticular waxes contain a lower proportion of long-chain alkanes. Direct measurements of transpiration, together with chlorophyll-leaching assays, indicate increased cuticular permeability of pe leaves. Genetic mapping revealed that the pe locus represents a new allele of CUTIN DEFICIENT2 (CD2), a member of the class IV homeodomain-leucine zipper gene family, previously only associated with cutin deficiency in tomato fruit. CD2 is preferentially expressed in epidermal cells of tomato stems and is a homolog of Arabidopsis (Arabidopsis thaliana) ANTHOCYANINLESS2 (ANL2). Analysis of cuticle composition in leaves of anl2 revealed that cutin accumulates to approximately 60% of the levels observed in wild-type Arabidopsis. Together, these data provide new insight into the role of CD2 and ANL2 in regulating diverse metabolic pathways and in particular, those associated with epidermal cells.

  8. Interobserver variability in the assessment of aneurysm occlusion with the WEB aneurysm embolization system.

    PubMed

    Fiorella, David; Arthur, Adam; Byrne, James; Pierot, Laurent; Molyneux, Andy; Duckwiler, Gary; McCarthy, Thomas; Strother, Charles

    2015-08-01

    The WEB (WEB aneurysm embolization system, Sequent Medical, Aliso Viejo, California, USA) is a self-expanding, nitinol, mesh device designed to achieve aneurysm occlusion after endosaccular deployment. The WEB Occlusion Scale (WOS) is a standardized angiographic assessment scale for reporting aneurysm occlusion achieved with intrasaccular mesh implants. This study was performed to assess the interobserver variability of the WOS. Seven experienced neurovascular specialists were trained to apply the WOS. These physicians independently reviewed angiographic image sets from 30 patients treated with the WEB under blinded conditions. No additional clinical information was provided. Raters graded each image according to the WOS (complete occlusion, residual neck or residual aneurysm). Final statistics were calculated using the dichotomous outcomes of complete occlusion or incomplete occlusion. The interobserver agreement was measured by the generalized κ statistic. In this series of 30 test case aneurysms, observers rated 12-17 as completely occluded, 3-9 as nearly completely occluded, and 9-11 as demonstrating residual aneurysm filling. Agreement was perfect across all seven observers for the presence or absence of complete occlusion in 22 of 30 cases. Overall, interobserver agreement was substantial (κ statistic 0.779 with a 95% CI of 0.700 to 0.857). The WOS allows a consistent means of reporting angiographic occlusion for aneurysms treated with the WEB device. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. miR-203 modulates epithelial differentiation of human embryonic stem cells towards epidermal stratification.

    PubMed

    Nissan, Xavier; Denis, Jérôme Alexandre; Saidani, Manoubia; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

    2011-08-15

    The molecular mechanisms controlling the differentiation of human basal keratinocyte stem cells towards the epidermis are well characterized, whereas the earliest process leading to the specification of embryonic stem cells into keratinocytes is still not well understood. MicroRNAs are regulators of many cellular events, but evidence for microRNA acting on the differentiation of human embryonic stem cells into a specific lineage has been elusive. By using our recent protocol for obtaining functional keratinocytes from hESC, we attempted to analyze the role of microRNAs in the early stages of epidermal differentiation. Thus, we identified a set of 5 microRNAs, namely miR-200a, miR-200b, miR-203, miR-205 and miR-429, that are specifically overexpressed during the early stages of the differentiation process. Interestingly, our functional analyses revealed an instrumental role of miR-203, which had been previously shown to play a key role during the formation of the pluristratified epidermis by basal keratinocyte stem cells, in the early keratinocyte commitment. These results highlight the determinant and unique role of miR-203 during the entire process of epidermal development by extending its spectrum of action from the early commitment of embryonic stem cells to ultimate differentiation of the organ. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. An Investigation of the Posterior Component of Occlusal Force

    DTIC Science & Technology

    1994-05-01

    of the hemostat allowed subjects to consistently orient the bite force transducer parallel to the occIusal plane , thus allowing the bite force to be...the anterior component of occlusal force was influenced by the steepness of the occlusal plane . Southard et al (1989) was the first to quantify the...young adult males yielded higher mean maximum bite forces at 20 mm opening and at 40 mm opening. The authors suggested that orientation and function of

  11. Dental Occlusion and Ophthalmology: A Literature Review

    PubMed Central

    Marchili, Nicola; Ortu, Eleonora; Pietropaoli, Davide; Cattaneo, Ruggero; Monaco, Annalisa

    2016-01-01

    Stomatognathic system is strictly correlated to other anatomical regions; many studies investigated relationship between temporomandibular joint and posture, several articles describe cranio-facial pain from dental causes, such as trigger points. Until now less interest has been given to connections between dental occlusion and ophthalmology, even if they are important and involving. Clinical experience in dental practice claims that mandibular latero-deviation is connected both to eye dominance and to defects of ocular convergence. The trigeminal nerve is the largest and most complex of the twelve cranial nerves. The trigeminal system represents the connection between somitic structures and those derived from the branchial arches, collecting the proprioception from both somitic structures and oculomotor muscles. The intermedius nucleus of the medulla is a small perihypoglossal brainstem nucleus, which acts to integrate information from the head and neck and relays it on to the nucleus of the solitary tract where autonomic responses are generated. This intriguing neurophysiological web led our research group to investigate anatomical and functional associations between dental occlusion and vision. In conclusion, nervous system and functional pathways strictly connect vision and dental occlusion, and in the future both dentists and oculists should be more and more aware of this correlation for a better diagnosis and therapy. PMID:27733873

  12. Sperm characteristics and teratology in rats following vas deferens occlusion with RISUG and its reversal.

    PubMed

    Lohiya, N K; Suthar, R; Khandelwal, A; Goyal, S; Ansari, A S; Manivannan, B

    2010-02-01

    The functional success of the reversal of vas occlusion by styrene maleic anhydride (RISUG), using the solvent vehicle, Dimethyl Sulphoxide (DMSO), has been investigated. Reversal with DMSO was carried out in Wistar albino rats 90 days after bilateral vas occlusion. The body weight, organ weight, sperm characteristics, fertility test and teratology, including skeletal morphology were evaluated in vas occlusion and reversal animals and in F(1) progenies to assess the functional success of the occlusion and reversal. Body weight, organ weight and the cauda epididymal sperm characteristics of vas occlusion and reversal animals and of F(1) progenies were comparable to control. Ejaculated spermatozoa in the vaginal smear showed detached head/tail, acrosomal damage, bent midpiece, bent tail and morphological aberrations in sperm head after vas occlusion, which returned to normal, 90 days after reversal. Monthly fertility test, post-injection showed 0% fertility, which improved gradually and 100% fertility was achieved 90 days after reversal. The fertility/pregnancy/implantation record and skeletal morphology of the offspring were comparable to control. The results suggest functional success and safety of vas occlusion reversal by DMSO.

  13. Occlusal characteristics of children with hypertrophied adenoids in Nigeria.

    PubMed

    Osiatuma, Vivien Ijeoma; Otuyemi, Olayinka Donald; Kolawole, Kikelomo Adebanke; Ogunbanjo, Babatunde Ogunbiyi; Amusa, Yemisi Bola

    2015-03-01

    Nasorespiratory function and its relation to craniofacial growth are of great interest because of the basic biological relationship between form and function, and the accumulating findings of the relationship between mode of breathing, craniofacial growth and orthodontic treatment. The aim of this study was to evaluate the effect of adenoid hypertrophy and sociodemographic variables on the occlusion of children. A total of 180 subjects aged 3-12 years were selected at the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria. Ninety subjects had hypertrophied adenoids while 90 normal children served as the control group. Orthodontic examinations were carried out and impressions for study models taken. Occlusion was assessed in the anterior-posterior, transverse and vertical planes. Class I relationship was the most prevalent occlusion in both adenoid and control subjects (55.6% and 72.2%, respectively). The occurrence of class II division 1 was significantly higher among adenoid than control subjects (P=0.003). Posterior crossbites occurred significantly more in adenoid subjects in the 9-12 years category. In the vertical plane, the occurrence of deep bite was significantly greater in male than female adenoid subjects. Age had a statistically significant but weak correlation with anterior open bite (r=0.37). Age and BMI also had significant though weak correlations with posterior crossbite in female adenoid subjects (r=0.39 and r=0.36, respectively). Regression analysis also showed that age had a significant effect on the occurrence of anterior open bite, while BMI had a significant effect on the occurrence of class II occlusion in adenoid subjects (P<0.05). The presence of hypertrophied adenoids affects the occlusion in the three planes. Age and BMI have significant effects on the occurrence of anterior open bite and class II division 1 malocclusion respectively in adenoid subjects. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Root growth regulation and gravitropism in maize roots does not require the epidermis

    NASA Technical Reports Server (NTRS)

    Bjorkman, T.; Cleland, R. E.

    1991-01-01

    We have earlier published observations showing that endogenous alterations in growth rate during gravitropism in maize roots (Zea mays L.) are unaffected by the orientation of cuts which remove epidermal and cortical tissue in the growing zone (Bjorkman and Cleland, 1988, Planta 176, 513-518). We concluded that the epidermis and cortex are not essential for transporting a growth-regulating signal in gravitropism or straight growth, nor for regulating the rate of tissue expansion. This conclusion has been challenged by Yang et al. (1990, Planta 180, 530-536), who contend that a shallow girdle around the entire perimeter of the root blocks gravitropic curvature and that this inhibition is the result of a requirement for epidermal cells to transport the growth-regulating signal. In this paper we demonstrate that the entire epidermis can be removed without blocking gravitropic curvature and show that the position of narrow girdles does not affect the location of curvature. We therefore conclude that the epidermis is not required for transport of a growth-regulating substance from the root cap to the growing zone, nor does it regulate the growth rate of the elongating zone of roots.

  15. SWIR reflectance imaging of demineralization on the occlusal surfaces of teeth beyond 1700 nm

    NASA Astrophysics Data System (ADS)

    Ng, Chung; Simon, Jacob C.; Fried, Daniel; Darling, Cynthia L.

    2018-02-01

    Most new lesions are found in the pits and fissures of the occlusal surface. Radiographs have extremely low sensitivity for early occlusal decay and by the time the lesion is severe enough on a radiograph it typically has penetrated well into the dentin and surgical intervention is required. The occlusal surfaces are heavily stained and visual and tactile methods for their detection also have poor sensitivity and specificity. Previous studies at wavelengths beyond 1300-nm have demonstrated that stains are not visible and demineralization on the occlusal surfaces can be viewed without interference from stains. New extended range InGaAs near- IR cameras allow access to wavelengths beyond 1700-nm. The objective of this study was to determine how the contrast of occlusal lesions varies with wavelength from the visible to 2350-nm. The lesion contrast was measured in 55 extracted teeth with suspected occlusal lesions using reflectance measurements from 400- 2350-nm using Si and InGaAs imaging arrays. The highest lesion contrast in reflectance was measured at wavelengths greater than 1700-nm. Stains interfered significantly at wavelengths shorter than 1150-nm. This study indicates that the optimum wavelengths for reflectance imaging decay in the occlusal surfaces are greater than 1700-nm.

  16. Hypophosphatemic rickets associated with epidermal nevus syndrome and giant hairy nevus.

    PubMed

    Chou, Yen-Yin; Chao, Sheau-Chiou; Shiue, Chiou-Nan; Tsai, Wen-Hui; Lin, Shio-Jean

    2005-01-01

    The association of hypophosphatemic rickets and epidermal nevus or giant hairy nevus is rare. We report two patients with hypophosphatemic rickets, one associated with epidermal nevus syndrome and the other with giant hairy nevus, and describe their clinical features and variable response to treatment. The abnormal nevus tissue may have contributed to the pathogenesis of hypophosphatemic rickets. We did not find a PHEX gene mutation in these two patients, and the mechanism for their rickets may be different from that in X-linked hypophosphatemic rickets.

  17. Internalization Mechanisms of the Epidermal Growth Factor Receptor after Activation with Different Ligands

    PubMed Central

    Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe; van Deurs, Bo; Grøvdal, Lene Melsæther

    2013-01-01

    The epidermal growth factor receptor (EGFR) regulates normal growth and differentiation, but dysregulation of the receptor or one of the EGFR ligands is involved in the pathogenesis of many cancers. There are eight ligands for EGFR, however most of the research into trafficking of the receptor after ligand activation focuses on the effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist. Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF) or betacellulin (BTC) was only partial. In contrast, clathrin knockdown fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand-induced endocytosis of the EGFR. We suggest that EGF and TGF-α lead to EGFR endocytosis mainly via the clathrin-mediated pathway. Furthermore, we suggest that HB-EGF and BTC also lead to EGFR endocytosis via a clathrin-mediated pathway, but can additionally use an unidentified internalization pathway or better recruit the small amount of clathrin remaining after clathrin knockdown. PMID:23472148

  18. Influence of occlusal plane inclination and mandibular deviation on esthetics

    PubMed Central

    Corte, Cristiane Cherobini Dalla; da Silveira, Bruno Lopes; Marquezan, Mariana

    2015-01-01

    Objective: The aim of this study was to assess the degree of perception of occlusal plane inclination and mandibular deviation in facial esthetics, assessed by laypeople, dentists and orthodontists. Methods: A woman with 5.88° of inclination and 5.54 mm of mandibular deviation was selected and, based on her original photograph, four new images were created correcting the deviations and creating more symmetric faces and smiles. Examiners assessed the images by means of a questionnaire. Their opinions were compared by qualitative and quantitative analyses. Results: A total of 45 laypeople, 27 dentists and 31 orthodontists filled out the questionnaires. All groups were able to perceive the asymmetry; however, orthodontists were more sensitive, identifying asymmetries as from 4.32° of occlusal plane inclination and 4.155 mm of mandibular deviation (p< 0.05). The other categories of evaluators identified asymmetries and assigned significantly lower grades, starting from 5.88° of occlusal plane inclination and 5.54 mm of mandibular deviation (p< 0.05). Conclusion: Occlusal plane inclination and mandibular deviation were perceived by all groups, but orthodontists presented higher perception of deviations. PMID:26560821

  19. The Antiaging Properties of Andrographis paniculata by Activation Epidermal Cell Stemness.

    PubMed

    You, Jiyoung; Roh, Kyung-Baeg; Li, Zidan; Liu, Guangrong; Tang, Jian; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

    2015-09-22

    Andrographis paniculata (A. paniculata, Chuanxinlian), a medicinal herb with an extremely bitter taste that is native to China and other parts of Southeast Asia, possesses immense therapeutic value; however, its therapeutic properties have rarely been applied in the field of skin care. In this study, we investigated the effect of an A. paniculata extract (APE) on human epidermal stem cells (EpSCs), and confirmed its anti-aging effect through in vitro, ex vivo, and in vivo study. An MTT assay was used to determine cell proliferation. A flow cytometric analysis, with propidium iodide, was used to evaluate the cell cycle. The expression of integrin β1 (CD29), the stem cell marker, was detected with antibodies, using flow cytometry in vitro, and immunohistochemical assays in ex vivo. Type 1 collagen and VEGF (vascular endothelial growth factor) were measured using an enzyme-linked immunosorbent assay (ELISA). During the clinical study, skin hydration, elasticity, wrinkling, sagging, and dermal density were evaluated before treatment and at four and eight weeks after the treatment with the test product (containing the APE) on the face. The proliferation of the EpSCs, treated with the APE, increased significantly. In the cell cycle analysis, the APE increased the G2/M and S stages in a dose-dependent manner. The expression of integrin β1, which is related to epidermal progenitor cell expansion, was up-regulated in the APE-treated EpSCs and skin explants. In addition, the production of VEGF in the EpSCs increased significantly in response to the APE treatment. Consistent with these results, the VEGF and APE-treated EpSCs conditioned medium enhanced the Type 1 collagen production in normal human fibroblasts (NHFs). In the clinical study, the APE improved skin hydration, dermal density, wrinkling, and sagging significantly. Our findings revealed that the APE promotes a proliferation of EpSCs, through the up-regulation of the integrin β1 and VEGF expression. The VEGF

  20. Branch retinal arterial occlusion.

    PubMed

    Subedi, S; Shrestha, C

    2010-01-01

    Retinal arterial occlusion is an ocular emergency in which visual prognosis is poor mostly due to late presentation of the patient and macular involvement. The casee described, in this report is ane incidence of Branch Retinal Arterial Occlusion in a 22 year old female with grade II Mitral Regurgitation. The patiente presented witha complaint of painless, diminution of vision in the right eyn. She also presented with perception of black shadow in the superior visual fiel n of the same eye5 for five days. There was no significant systemic ord personal history. Her visual acuity at presentation was 6/60 and 6/6 in the right and left eyes,y which did not improve with glasses or pin-hole. Anterior segment including papillary reaction was normal in both eyes while Fundus examination of the right eye revealed retinal whitening inside the inferotemporal vascular arcade that was encroaching foveolar avascular zone. Visual field defect was detected at superonasally inside arhade but Fundus Fluorescence Angiography was normal. An echoycardiograph revealed grade II Mitral Regurgitation. The patient was kept on observation and after two2 days of follow-up, vision in the right eye was improved to 6/6 unaided but visual field defect was remained same.

  1. Acute Central Retinal Vein Occlusion Secondary to Reactive Thrombocytosis after Splenectomy

    PubMed Central

    Oncel Acir, Nursen; Borazan, Mehmet

    2014-01-01

    The diagnosis and treatment of central retinal vein occlusion was reported in a young patient. Central retinal vein occlusion was probably related to secondary to reactive thrombocytosis after splenectomy. The patient was treated with steroids for papilledema and administered coumadin and aspirin. The symptoms resolved, and the findings returned to normal within three weeks. Current paper emphasizes that, besides other well-known thrombotic events, reactive thrombocytosis after splenectomy may cause central retinal vein occlusion, which may be the principal symptom of this risky complication. Thus, it can be concluded that followup for thrombocytosis and antithrombotic treatment, when necessary, are essential for these cases. PMID:25276452

  2. Retinal vein occlusion: pathophysiology and treatment options.

    PubMed

    Karia, Niral

    2010-07-30

    This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.

  3. [Retrospective analysis of patients with thrombocytopenia after patent ductus arteriosus interventional occlusion].

    PubMed

    Liao, Qi-wei; Zhang, Wei-hua; Guang, Xue-feng; Lu, Yi-bing

    2013-03-01

    To explore the risk factors of patent ductus arteriosus (PDA) patients with thrombocytopenia after PDA interventional occlusion. Thrombocytopenia occurred in 14 out of 350 patients underwent PDA occlusion. Age, gender, body weight, PDA size, occluder size, mean pulmonary arterial pressure, the dose of heparin, the manufacturer of occluder, residual shunt after operation were analyzed. The recovery time of different grades of thrombocytopenia was observed. Multivariate logistic regression showed that the PDA size (OR = 2.238, P < 0.05), the dose of heparin (OR = 3.247, P < 0.05), residual shunt after operation (OR = 1.912, P < 0.01) were the independent risk factors of thrombocytopenia after PDA occlusion. The recovery time of mild thrombocytopenia was (7 ± 2) days without treatment. The recovery time of moderate thrombocytopenia was (12 ± 4) days with glucocorticoids treatment. The recovery time of severe thrombocytopenia was (21 ± 7) days with platelet transfusion. The occluder size, dose of heparin, residual shunt are the independent risk factors of thrombocytopenia after PDA interventional occlusion. Recover time of thrombocytopenia after PDA interventional occlusion is closely related to the severity of thrombocytopenia.

  4. Influence of stabilization occlusal splint on craniocervical relationships. Part I: Cephalometric analysis.

    PubMed

    Moya, H; Miralles, R; Zuñiga, C; Carvajal, R; Rocabado, M; Santander, H

    1994-01-01

    This study was conducted in order to determine the effect of an occlusal splint on craniocervical relationships, in subjects with muscle spasms in the sternocleidomastoid and trapezius muscles. A full-arch maxillary stabilization occlusal splint was made for each of the 15 subjects. Two lateral craniocervical radiographs were taken for each subject, with and without an occlusal splint. Cephalometric analysis showed that the splint caused a significant extension of the head on the cervical spine. There was also a significant decrease in the cervical spine lordosis in the first, second and third cervical segment. These cervical changes could be a compensation mechanism caused by the extension of the cranium on the upper cervical spine. The change in the curvature implies that it is necessary to periodically evaluate the changes occurring in the craniocervical relationships after the occlusal splint has been inserted.

  5. Using occlusal wear information and finite element analysis to investigate stress distributions in human molars

    PubMed Central

    Benazzi, Stefano; Kullmer, Ottmar; Grosse, Ian R; Weber, Gerhard W

    2011-01-01

    Simulations based on finite element analysis (FEA) have attracted increasing interest in dentistry and dental anthropology for evaluating the stress and strain distribution in teeth under occlusal loading conditions. Nonetheless, FEA is usually applied without considering changes in contacts between antagonistic teeth during the occlusal power stroke. In this contribution we show how occlusal information can be used to investigate the stress distribution with 3D FEA in lower first molars (M1). The antagonistic crowns M1 and P2–M1 of two dried modern human skulls were scanned by μCT in maximum intercuspation (centric occlusion) contact. A virtual analysis of the occlusal power stroke between M1 and P2–M1 was carried out in the Occlusal Fingerprint Analyser (OFA) software, and the occlusal trajectory path was recorded, while contact areas per time-step were visualized and quantified. Stress distribution of the M1 in selected occlusal stages were analyzed in strand7, considering occlusal information taken from OFA results for individual loading direction and loading area. Our FEA results show that the stress pattern changes considerably during the power stroke, suggesting that wear facets have a crucial influence on the distribution of stress on the whole tooth. Grooves and fissures on the occlusal surface are seen as critical locations, as tensile stresses are concentrated at these features. Properly accounting for the power stroke kinematics of occluding teeth results in quite different results (less tensile stresses in the crown) than usual loading scenarios based on parallel forces to the long axis of the tooth. This leads to the conclusion that functional studies considering kinematics of teeth are important to understand biomechanics and interpret morphological adaptation of teeth. PMID:21615398

  6. RANKL, Osteopontin, and Osteoclast Homeostasis in a Hyper-Occlusion Mouse Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Walker, Cameron G.; Ito, Yoshihiro; Dangaria, Smit

    2010-11-15

    The biological mechanisms that maintain the position of teeth in their sockets establish a dynamic equilibrium between bone resorption and apposition. In order to reveal some of the dynamics involved in the tissue responses towards occlusal forces on periodontal ligament (PDL) and alveolar bone homeostasis, we developed the first mouse model of hyperocclusion. Swiss-Webster mice were kept in hyperocclusion for 0, 3, 6, and 9 d. Morphological and histological changes in the periodontium were assessed using micro-computed tomography (micro-CT) and ground sections with fluorescent detection of vital dye labels. Sections were stained for tartrate-resistant acid phosphatase, and the expression ofmore » receptor activator of nuclear factor-{kappa}B ligand (RANKL) and osteopontin (OPN) was analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). Traumatic occlusion resulted in enamel surface abrasion, inhibition of alveolar bone apposition, significant formation of osteoclasts at 3, 6 and 9 d, and upregulation of OPN and RANKL. Data from this study suggest that both OPN and RANKL contribute to the stimulation of bone resorption in the hyperocclusive state. In addition, we propose that the inhibition of alveolar bone apposition by occlusal forces is an important mechanism for the control of occlusal height that might work in synergy with RANKL-induced bone resorption to maintain normal occlusion.« less

  7. Lysophosphatidic acid stimulates epidermal growth factor-family ectodomain shedding and paracrine signaling from human lung fibroblasts.

    PubMed

    Shiomi, Tetsuya; Boudreault, Francis; Padem, Nurcicek; Higashiyama, Shigeki; Drazen, Jeffrey M; Tschumperlin, Daniel J

    2011-01-01

    Lysophospatidic acid (LPA) is a bioactive lipid mediator implicated in tissue repair and wound healing. It mediates diverse functional effects in fibroblasts, including proliferation, migration and contraction, but less is known about its ability to evoke paracrine signaling to other cell types involved in wound healing. We hypothesized that human pulmonary fibroblasts stimulated by LPA would exhibit ectodomain shedding of epidermal growth factor receptor (EGFR) ligands that signal to lung epithelial cells. To test this hypothesis, we used alkaline phosphatase-tagged EGFR ligand plasmids transfected into lung fibroblasts, and enzyme-linked immunosorbent assays to detect shedding of native ligands. LPA induced shedding of alkaline phosphatase-tagged heparin-binding epidermal growth factor (HB-EGF), amphiregulin, and transforming growth factor-a; non-transfected fibroblasts shed amphiregulin and HBEGF under baseline conditions, and increased shedding of HB-EGF in response to LPA. Treatment of fibroblasts with LPA resulted in elevated phosphorylation of extracellular signal-regulated kinase 1/2, enhanced expression of mRNA for c-fos, HB-EGF and amphiregulin, and enhanced proliferation at 96 hours. However, none of these fibroblast responses to LPA required ectodomain shedding or EGFR activity. To test the ability of LPA to stimulate paracrine signaling from fibroblasts, we transferred conditioned medium from LPA-stimulated cells, and found enhanced EGFR and extracellular signal-regulated kinase 1/2 phosphorylation in reporter A549 cells in excess of what could be accounted for by transferred LPA alone. These data show that LPA mediates EGF-family ectodomain shedding, resulting in enhanced paracrine signaling from lung fibroblasts to epithelial cells. © 2011 by the Wound Healing Society.

  8. Genetics Home Reference: pulmonary veno-occlusive disease

    MedlinePlus

    ... G, Humbert M. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine (Baltimore). 2008 Jul;87(4):220-33. doi: ...

  9. Minimally invasive per-catheter occlusion and dilation procedures for congenital cardiovascular abnormalities in dogs.

    PubMed

    Tobias, Anthony H; Stauthammer, Christopher D

    2010-07-01

    With ever-increasing sophistication of veterinary cardiology, minimally invasive per-catheter occlusion and dilation procedures for the treatment of various congenital cardiovascular abnormalities in dogs have become not only available, but mainstream. Much new information about minimally invasive per-catheter patent ductus arteriosus occlusion has been published and presented during the past few years. Consequently, patent ductus arteriosus occlusion is the primary focus of this article. Occlusion of other less common congenital cardiac defects is also briefly reviewed. Balloon dilation of pulmonic stenosis, as well as other congenital obstructive cardiovascular abnormalities is discussed in the latter part of the article.

  10. Occlusal Classification in Relation to Original Cleft Width in Patients With Unilateral Cleft Lip and Palate.

    PubMed

    Huang, Andrew H; Patel, Kamlesh B; Maschhoff, Clayton W; Huebener, Donald V; Skolnick, Gary B; Naidoo, Sybill D; Woo, Albert S

    2015-09-01

    To determine a correlation between the width of the cleft palate measured at the time of lip adhesion, definitive lip repair, and palatoplasty and the subsequent occlusal classification of patients born with unilateral cleft lip and palate. Retrospective, observational study. Referral, urban, children's hospital Participants : Dental models and records of 270 patients were analyzed. None. Angle occlusion classification. The mean age at which occlusal classification was determined was 11 ± 0.3 years. Of the children studies, 84 were diagnosed with Class I or II occlusion, 67 were diagnosed with Class III occlusion, and 119 were lost to follow up or transferred care. Mean cleft widths were significantly larger in subjects with Class III occlusion for all measures at time of lip adhesion and definitive lip repair (P < .02). At time of palatoplasty, cleft widths were significantly greater at the alveolus (P = .025) but not at the midportion of the hard palate (P = .35) or posterior hard palate (P = .10). Cleft widths from the lip through to the posterior hard palate are generally greater in children who are diagnosed with Class III occlusion later in life. Notably, the alveolar cleft width is significantly greater at each time point for patients who went on to develop Class III occlusion. There were no significant differences in cleft widths between patients diagnosed later with Class I and Class II occlusions.

  11. Comparison of NIRS, laser Doppler flowmetry, photoplethysmography, and pulse oximetry during vascular occlusion challenges.

    PubMed

    Abay, T Y; Kyriacou, P A

    2016-04-01

    Monitoring changes in blood volume, blood flow, and oxygenation in tissues is of vital importance in fields such as reconstructive surgery and trauma medicine. Near infrared spectroscopy (NIRS), laser Doppler (LDF) flowmetry, photoplethysmography (PPG), and pulse oximetry (PO) contribute to such fields due to their safe and noninvasive nature. However, the techniques have been rarely investigated simultaneously or altogether. The aim of this study was to investigate all the techniques simultaneously on healthy subjects during vascular occlusion challenges. Sensors were attached on the forearm (NIRS and LDF) and fingers (PPG and PO) of 19 healthy volunteers. Different degrees of vascular occlusion were induced by inflating a pressure cuff on the upper arm. The responses of tissue oxygenation index (NIRS), tissue haemoglobin index (NIRS), flux (LDF), perfusion index (PPG), and arterial oxygen saturation (PO) have been recorded and analyzed. Moreover, the optical densities were calculated from slow varying dc PPG, in order to distinguish changes in venous blood volumes. The indexes showed significant changes (p  <  0.05) in almost all occlusions, either venous or over-systolic occlusions. However, differentiation between venous and arterial occlusion by LDF may be challenging and the perfusion index (PI) may not be adequate to indicate venous occlusions. Optical densities may be an additional tool to detect venous occlusions by PPG.

  12. micro RNA 172 (miR172) signals epidermal infection and is expressed in cells primed for bacterial invasion in Lotus japonicus roots and nodules.

    PubMed

    Holt, Dennis B; Gupta, Vikas; Meyer, Dörte; Abel, Nikolaj B; Andersen, Stig U; Stougaard, Jens; Markmann, Katharina

    2015-10-01

    Legumes interact with rhizobial bacteria to form nitrogen-fixing root nodules. Host signalling following mutual recognition ensures a specific response, but is only partially understood. Focusing on the stage of epidermal infection with Mesorhizobium loti, we analysed endogenous small RNAs (sRNAs) of the model legume Lotus japonicus to investigate their involvement in host response regulation. We used Illumina sequencing to annotate the L. japonicus sRNA-ome and isolate infection-responsive sRNAs, followed by candidate-based functional characterization. Sequences from four libraries revealed 219 novel L. japonicus micro RNAs (miRNAs) from 114 newly assigned families, and 76 infection-responsive sRNAs. Unlike infection-associated coding genes such as NODULE INCEPTION (NIN), a micro RNA 172 (miR172) isoform showed strong accumulation in dependency of both Nodulation (Nod) factor and compatible rhizobia. The genetics of miR172 induction support the existence of distinct epidermal and cortical signalling events. MIR172a promoter activity followed a previously unseen pattern preceding infection thread progression in epidermal and cortical cells. Nodule-associated miR172a expression was infection-independent, representing the second of two genetically separable activity waves. The combined data provide a valuable resource for further study, and identify miR172 as an sRNA marking successful epidermal infection. We show that miR172 acts upstream of several APETALA2-type (AP2) transcription factors, and suggest that it has a role in fine-tuning AP2 levels during bacterial symbiosis. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  13. Retinal vein occlusion: pathophysiology and treatment options

    PubMed Central

    Karia, Niral

    2010-01-01

    This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms. PMID:20689798

  14. Near-IR and CP-OCT Imaging of Suspected Occlusal Caries Lesions

    PubMed Central

    Simon, Jacob C.; Kang, Hobin; Staninec, Michal; Jang, Andrew T.; Chan, Kenneth H.; Darling, Cynthia L.; Lee, Robert C.; Fried, Daniel

    2017-01-01

    Introduction Radiographic methods have poor sensitivity for occlusal lesions and by the time the lesions are radiolucent they have typically progressed deep into the dentin. New more sensitive imaging methods are needed to detect occlusal lesions. In this study, cross-polarization optical coherence tomography (CP-OCT) and near-IR imaging were used to image questionable occlusal lesions (QOC's) that were not visible on radiographs but had been scheduled for restoration on 30 test subjects. Methods Near-IR reflectance and transillumination probes incorporating a high definition InGaAs camera and near-IR broadband light sources were used to acquire images of the lesions before restoration. The reflectance probe utilized cross-polarization and operated at wavelengths from 1500–1700-nm where there is an increase in water absorption for higher contrast. The transillumination probe was operated at 1300-nm where the transparency of enamel is highest. Tomographic images (6×6×7 mm3) of the lesions were acquired using a high-speed swept-source CP-OCT system operating at 1300-nm before and after removal of the suspected lesion. Results Near-IR reflectance imaging at 1500–1700-nm yielded significantly higher contrast (p<0.05) of the demineralization in the occlusal grooves compared with visible reflectance imaging. Stains in the occlusal grooves greatly reduced the lesion contrast in the visible range yielding negative values. Only half of the 26 lesions analyzed showed the characteristic surface demineralization and increased reflectivity below the dentinal-enamel junction (DEJ) in 3D OCT images indicative of penetration of the lesion into the dentin. Conclusion This study demonstrates that near-IR imaging methods have great potential for improving the early diagnosis of occlusal lesions. PMID:28339115

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

    PubMed

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

    2016-06-01

    A long-standing research focus in phytology has been to understand how plants allocate leaf epidermal space to stomata in order to achieve an economic balance between the plant's carbon needs and water use. Here, we present a quantitative theoretical framework to predict allometric relationships between morphological stomatal traits in relation to leaf gas exchange and the required allocation of epidermal area to stomata. Our theoretical framework was derived from first principles of diffusion and geometry based on the hypothesis that selection for higher anatomical maximum stomatal conductance (gsmax ) involves a trade-off to minimize the fraction of the epidermis that is allocated to stomata. Predicted allometric relationships between stomatal traits were tested with a comprehensive compilation of published and unpublished data on 1057 species from all major clades. In support of our theoretical framework, stomatal traits of this phylogenetically diverse sample reflect spatially optimal allometry that minimizes investment in the allocation of epidermal area when plants evolve towards higher gsmax . Our results specifically highlight that the stomatal morphology of angiosperms evolved along spatially optimal allometric relationships. We propose that the resulting wide range of viable stomatal trait combinations equips angiosperms with developmental and evolutionary flexibility in leaf gas exchange unrivalled by gymnosperms and pteridophytes. © 2016 The Authors New Phytologist © 2016 New Phytologist Trust.

  16. Epidermal carbonic anhydrase activity and exoskeletal metal content during the molting cycle of the blue crab, Callinectes sapidus.

    PubMed

    Calhoun, Stacy; Zou, Enmin

    2016-03-01

    During the crustacean molting cycle, the exoskeleton is first mineralized in postmolt and intermolt and then presumably demineralized in premolt in order for epidermal retraction to occur. The mineralization process calls for divalent metal ions, such as Ca(2+) and Mg(2+) , and bicarbonate ions whereas protons are necessary for dissolution of carbonate salts. Carbonic anhydrase (CA) has been suggested to be involved in exoskeletal mineralization by providing bicarbonate ions through catalyzing the reaction of carbon dioxide hydration. However, results of earlier studies on the role of epidermal CA in metal incorporation in crustacean exoskeleton are not consistent. This study was aimed to provide further evidence to support the notion that epidermal CA is involved in exoskeletal mineralization using the blue crab, Callinectes sapidus (Rathbun 1896), as the model crustacean. Significant increases first in calcium and magnesium then in manganese post-ecdysis indicate significant metal deposition during postmolt and intermolt. Significant positive correlation between calcium or magnesium content and epidermal CA activity in postmolt and intermolt constitutes evidence that CA is involved in the mineralization of the crustacean exoskeleton. Additionally, we proposed a hypothetical model to describe the role of epidermal CA in both mineralization and demineralization of the exoskeleton based on the results of epidermal CA activity and exoskeletal metal content during the molting cycle. Furthermore, we found that the pattern of epidermal CA activity during the molting cycle of C. sapidus is similar to that of ecdysteroids reported for the same species, suggesting that epidermal CA activity may be under control of the molting hormones. © 2016 Wiley Periodicals, Inc.

  17. Epidermal keratinocytes initiate wound healing and pro-inflammatory immune responses following percutaneous schistosome infection

    PubMed Central

    Bourke, Claire D.; Prendergast, Catriona T.; Sanin, David E.; Oulton, Tate E.; Hall, Rebecca J.; Mountford, Adrian P.

    2015-01-01

    Keratinocytes constitute the majority of cells in the skin’s epidermis, the first line of defence against percutaneous pathogens. Schistosome larvae (cercariae) actively penetrate the epidermis to establish infection, however the response of keratinocytes to invading cercariae has not been investigated. Here we address the hypothesis that cercariae activate epidermal keratinocytes to promote the development of a pro-inflammatory immune response in the skin. C57BL/6 mice were exposed to Schistosoma mansoni cercariae via each pinna and non-haematopoietic cells isolated from epidermal tissue were characterised for the presence of different keratinocyte sub-sets at 6, 24 and 96 h p.i. We identified an expansion of epidermal keratinocyte precursors (CD45−, CD326−, CD34+) within 24 h of infection relative to naïve animals. Following infection, cells within the precursor population displayed a more differentiated phenotype (α6integrin−) than in uninfected skin. Parallel immunohistochemical analysis of pinnae cryosections showed that this expansion corresponded to an increase in the intensity of CD34 staining, specifically in the basal bulge region of hair follicles of infected mice, and a higher frequency of keratinocyte Ki67+ nuclei in both the hair follicle and interfollicular epidermis. Expression of pro-inflammatory cytokine and stress-associated keratin 6b genes was also transiently upregulated in the epidermal tissue of infected mice. In vitro exposure of keratinocyte precursors isolated from neonatal mouse skin to excretory/secretory antigens released by penetrating cercariae elicited IL-1α and IL-1β production, supporting a role for keratinocyte precursors in initiating cutaneous inflammatory immune responses. Together, these observations indicate that S.mansoni cercariae and their excretory/secretory products act directly upon epidermal keratinocytes, which respond by initiating barrier repair and pro-inflammatory mechanisms similar to those

  18. Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles

    PubMed Central

    Feng, Zhi-Gang; Cortina, Miguel; Chesnutt, Jennifer KW; Han, Hai-Chao

    2017-01-01

    Tortuous microvessels alter blood flow and stimulate thrombosis but the physical mechanisms are poorly understood. Both tortuous microvessels and abnormally large platelets are seen in diabetic patients. Thus, the objective of this study was to determine the physical effects of arteriole tortuosity and platelet size on the microscale processes of thrombotic occlusion in microvessels. A new lattice-Boltzmann method-based discrete element model was developed to simulate the fluid flow field with fluid-platelet coupling, platelet interactions, thrombus formation, and thrombotic occlusion in tortuous arterioles. Our results show that vessel tortuosity creates high shear stress zones that activate platelets and stimulate thrombus formation. The growth rate depends on the level of tortuosity and the pressure and flow boundary conditions. Once thrombi began to form, platelet collisions with thrombi and subsequent activations were more important than tortuosity level. Thrombus growth narrowed the channel and reduced the flow rate. Larger platelet size leads to quicker decrease of flow rate due to larger thrombi that occluded the arteriole. This study elucidated the important roles that tortuosity and platelet size play in thrombus formation and occlusion in arterioles. PMID:29327739

  19. Measurement of periapical pressure created by occlusal loading.

    PubMed

    Dobó-Nagy, C; Fejérdy, P; Angyal, J; Harasztosi, L; Daróczi, L; Beke, D; Wesselink, P R

    2003-10-01

    To develop an in vitro model in which the pressure in the periapical tissues can be measured during loading. Extracted human maxillary central incisors were embedded in resin blocks that had physical characteristics similar to those of bone and periodontal ligament. Each tooth was loaded with 20, 40, 50, 60, 75, 85, 100, 200, 300 and 450 N vertical forces from the incisal edge of the crown on three consecutive occasions. A minute resistor embedded in the periapical space was used to detect apical pressure changes during occlusal loading. The ratio of apical pressure changes (DeltaP) to the loading force changes (DeltaF) was calculated. The periapical pressure detected was in direct proportion to the loading force. The mean value of DeltaP/DeltaF was 5.994 kPa N-1 (SD = 2.04). Direct proportionality was found between the coronal loading and the apical hydrostatic pressure. The DeltaP/DeltaF ratio determined in this study makes it easier to estimate the apical hydrostatic pressure values during occlusal loading of single-rooted teeth. In this study, the apical pressure generated under occlusal loading was the same magnitude as that estimated with the finite element method.

  20. Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility.

    PubMed

    Cipolat, Sara; Hoste, Esther; Natsuga, Ken; Quist, Sven R; Watt, Fiona M

    2014-05-05

    Atopic dermatitis can result from loss of structural proteins in the outermost epidermal layers, leading to a defective epidermal barrier. To test whether this influences tumour formation, we chemically induced tumours in EPI-/- mice, which lack three barrier proteins-Envoplakin, Periplakin, and Involucrin. EPI-/- mice were highly resistant to developing benign tumours when treated with 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The DMBA response was normal, but EPI-/- skin exhibited an exaggerated atopic response to TPA, characterised by abnormal epidermal differentiation, a complex immune infiltrate and elevated serum thymic stromal lymphopoietin (TSLP). The exacerbated TPA response could be normalised by blocking TSLP or the immunoreceptor NKG2D but not CD4+ T cells. We conclude that atopy is protective against skin cancer in our experimental model and that the mechanism involves keratinocytes communicating with cells of the immune system via signalling elements that normally protect against environmental assaults.DOI: http://dx.doi.org/10.7554/eLife.01888.001. Copyright © 2014, Cipolat et al.

  1. Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells.

    PubMed

    Gekle, Michael; Freudinger, Ruth; Mildenberger, Sigrid; Silbernagl, Stefan

    2002-04-01

    Epidermal growth factor (EGF) regulates cell proliferation, differentiation, and ion transport by using extracellular signal-regulated kinase (ERK)1/2 as a downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G protein-coupled receptors, growth hormone, and cytokines by means of transactivation. It has been suggested that steroids interact with peptide hormones, in part, by rapid, potentially nongenomic, mechanisms. Previously, we have shown that aldosterone modulates Na(+)/H(+) exchange in Madin-Darby canine kidney (MDCK) cells by means of ERK1/2 in a way similar to growth factors. Here, we tested the hypothesis that aldosterone uses the EGF-R as a heterologous signal transducer in MDCK cells. Nanomolar concentrations of aldosterone induce a rapid increase in ERK1/2 phosphorylation, cellular Ca(2+) concentration, and Na(+)/H(+) exchange activity similar to increases induced by EGF. Furthermore, aldosterone induced a rapid increase in EGF-R-Tyr phosphorylation, and inhibition of EGF-R kinase abolished aldosterone-induced signaling. Inhibition of ERK1/2 phosphorylation reduced the Ca(2+) response, whereas prevention of Ca(2+) influx did not abolish ERK1/2 phosphorylation. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.

  2. Diminished survival of human cytotrophoblast cells exposed to hypoxia/reoxygenation injury and associated reduction of heparin-binding epidermal growth factor-like growth factor.

    PubMed

    Leach, Richard E; Kilburn, Brian A; Petkova, Anelia; Romero, Roberto; Armant, D Randall

    2008-04-01

    The antiapoptotic action of heparin-binding epidermal growth factor (HBEGF)-like growth factor and its regulation by O(2) constitutes a key factor for trophoblast survival. The hypothesis that cytotrophoblast survival is compromised by exposure to hypoxia-reoxygenation (H/R) injury, which may contribute to preeclampsia and some missed abortions, prompted us to investigate HBEGF regulation and its role as a survival factor during H/R in cytotrophoblast cells. A transformed human first-trimester cytotrophoblast cell line HTR-8/SVneo was exposed to H/R (2% O(2) followed by 20% O(2)) and assessed for HBEGF expression and cell death. Cellular HBEGF declined significantly within 30 minutes of reoxygenation after culture at 2% O(2). H/R significantly reduced proliferation and increased cell death when compared with trophoblast cells cultured continuously at 2% or 20% O(2). Restoration of cell survival also was achieved by adding recombinant HBEGF during reoxygenation. HBEGF inhibited apoptosis through its binding to either human epidermal receptor (HER)-1 or HER4, its cognate receptors. These results provide evidence that cytotrophoblast exposure to H/R induces apoptosis and decreased cell proliferation. HBEGF accumulation is diminished under these conditions, whereas restoration of HBEGF signaling improves trophoblast survival.

  3. The effect of resting blood flow occlusion on exercise tolerance and W'.

    PubMed

    Broxterman, Ryan M; Craig, Jesse C; Ade, Carl J; Wilcox, Samuel L; Barstow, Thomas J

    2015-09-15

    It has previously been postulated that the anaerobic work capacity (W') may be utilized during resting blood flow occlusion in the absence of mechanical work. We tested the hypothesis that W' would not be utilized during an initial range of time following the onset of resting blood flow occlusion, after which W' would be utilized progressively more. Seven men completed blood flow occlusion constant power severe intensity handgrip exercise to task failure following 0, 300, 600, 900, and 1,200 s of resting blood flow occlusion. The work performed above critical power (CP) was not significantly different between the 0-, 300-, and 600-s conditions and was not significantly different from the total W' available. Significantly less work was performed above CP during the 1,200-s condition than the 900-s condition (P < 0.05), while both conditions were significantly less than the 0-, 300-, and 600-s conditions (P < 0.05). The work performed above CP during these conditions was significantly less than the total W' available (P < 0.05). The utilization of W' during resting blood flow occlusion did not begin until 751 ± 118 s, after which time W' was progressively utilized. The current findings demonstrate that W' is not utilized during the initial ∼751 s of resting blood flow occlusion, but is progressively utilized thereafter, despite no mechanical work being performed. Thus, the utilization of W' is not exclusive to exercise, and a constant amount of work that can be performed above CP is not the determining mechanism of W'. Copyright © 2015 the American Physiological Society.

  4. Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models.

    PubMed

    Smits, Jos P H; Niehues, Hanna; Rikken, Gijs; van Vlijmen-Willems, Ivonne M J J; van de Zande, Guillaume W H J F; Zeeuwen, Patrick L J M; Schalkwijk, Joost; van den Bogaard, Ellen H

    2017-09-19

    The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). Stratum corneum permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for in vitro studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.

  5. Voxel-Space Ambient Occlusion

    DTIC Science & Technology

    2012-02-01

    a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. a...represents the BRDF of the surface material, for incoming direction ψ and an outgoing direction. L(y) is the incoming radiance in the direction ψ from a...10-1-0338). Models come from the Stanford repository. References [BS09] L. Bavoil, M.Sainz Multi-layer dual-resolution screen-space ambient occlusion

  6. [Vemurafenib-induced toxic epidermal necrolysis].

    PubMed

    Wantz, M; Spanoudi-Kitrimi, I; Lasek, A; Lebas, D; Quinchon, J-F; Modiano, P

    2014-03-01

    Herein we report the first case of toxic epidermal necrolysis (TEN) occurring with use of vemurafenib. A 75-year-old female patient was being treated with vemurafenib for stage IV melanoma with BRAF V600E mutation. She suddenly presented fever, diffuse pruriginous maculopapular erythema, palpebral edema, palmar bulla, conjunctivitis, cheilitis and mucosal ulceration. The condition progressed towards detachment affecting 50% of the skin area. Cutaneous biopsy revealed lichenoid dermatosis, chiefly vesicular with numerous eosinophils. Direct immunofluorescence (IFD) was negative. Vemurafenib was the only drug to which the reaction was ascribable and we concluded on vemurafenib-induced TEN. To our knowledge, this is the first reported case of vemurafenib-induced TEN, but this adverse effect, although already described in the BRIM-3 study, appears rare in clinical practice. Other severe skin reactions have been described in the literature. These include a case of Stevens-Johnson syndrome in a female patient treated with vemurafenib and previously receiving ipilimumab. A more common occurrence is cutaneous reactions involving efflorescence of benign hyperkeratotic lesions, occasionally accompanied by authentic epidermal carcinoma or keratoacanthoma, and requiring regular dermatological monitoring of patients treated with vemurafenib. If maculopapular exanthema occurs under vemurafenib, continuation of this treatment should be reassessed since the risk of progression to a more serious condition such as TEN, as seen in the present case, cannot be ruled out. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Effects of retraction force and anchorage reinforcement on occlusal force: a model study.

    PubMed

    Kim, MoonHee; Seol, Kyung-sim; Lee, Yoonjung; Park, Jiman; Kim, Minji; Chun, Youn-Sic

    2014-10-01

    The aim of this study was to investigate the effects of retraction force and anchorage reinforcement with orthodontic mini implants on occlusal force. A strain gauge was attached to the palatal surface of the maxillary right first molar on an en masse retraction model. Occlusal forces were measured from this model, according to different retraction forces that were generated by elastic chain, under varied compressive forces (simulating masticatory forces). This retraction experiment was then performed again, after using anchorage reinforcement with an orthodontic mini implant. Occlusal force decreased as retraction force increased. The decrease showed a significant difference above 150g of retraction force (P < 0.05) and was more definite under compressive force higher than 150 N (P < 0.001). After anchorage reinforcement with the orthodontic mini implant, however, occlusal force did not significantly decrease with increasing retraction force. Significant differences in occlusal force were noted between the conditions with and without anchorage reinforcement when the applied retraction force was greater than 200g. Occlusal force tends to decrease during retraction, and this decrease can be prevented by anchorage reinforcement with orthodontic mini implants. Further investigation on the actual masticatory process in humans is required for more clear clinical implication. © The Author 2013. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. [Clinical evaluation of preadjusted appliance based on Chinese normal occlusion].

    PubMed

    Chen, Lin; Gao, Xue-Mei; Zeng, Xiang-Long

    2008-02-01

    To evaluate the effect of the preadjusted appliance (Z1 appliance) based on Chinese normal occlusion. Thirty non-extraction patients were treated with Z1 appliance. No wire bending was made during treatment. The results of these 30 cases had been evaluated by five senior orthodontists. Models were analysed quantitatively to testify and evaluate the efficiency of the appliance. The average score for post-treatment models was 91.2 (total score was 100). The model measurements indicated that average projective distance on occlusal plane between proximal contact points of adjacent teeth was less than 0.3 mm, which demonstrated good alignment. The prominence of crowns was almost coincident with the data of Chinese normal occlusion. For the average tip of most teeth, there was no statistical difference between the study group and the normal control group. The crown torque variation tendency from anterior to posterior was similar to that in the subjects with normal occlusion. However, the cases treated with Z1 appliance achieved more negative torque in the lower posterior segment. The result of the non-extraction patients treated with Z1 appliance was quite satisfied. Wire bending could be reduced during treatment. It was necessary to adjust the crown torque values for lower posterior teeth.

  9. Etanercept therapy for toxic epidermal necrolysis.

    PubMed

    Paradisi, Andrea; Abeni, Damiano; Bergamo, Fabio; Ricci, Francesco; Didona, Dario; Didona, Biagio

    2014-08-01

    Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. To describe a case series of patients with TEN treated with a single dose of etanercept. We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan-Meier method. All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. This is a small, uncontrolled case series. These preliminary results suggest the possibility that tumor necrosis factor-alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  10. Central retinal artery occlusion in an ANCA negative Churg-Strauss syndrome patient.

    PubMed

    Türkçüoğlu, Peykan; Isik, Ahmet; Deniz, Nurettin; Turgut, Burak; Kan, Elif Kiliç

    2007-12-01

    To describe a central retinal artery occlusion in a patient with antineutrophil cytoplasmic antibody (ANCA) negative Churg-Strauss syndrome. Review of clinical and laboratory findings of a 44-year-old woman with ANCA negative Churg-Strauss syndrome that developed sudden vision loss in left eye. Left central retinal artery occlusion was diagnosed by retinal whitening, a cherry-red spot, and delayed arterial filling on fluorescein angiography. Perinuclear ANCA and cytoplasmic ANCA were negative. Central retinal artery occlusion can occur in ANCA negative Churg-Strauss syndrome. Patients with this diagnosis should be considered for prophylactic high dose corticosteroid, regardless of their ANCA status.

  11. OCT aspects of dental hard tissue changes induced by excessive occlusal forces

    NASA Astrophysics Data System (ADS)

    Scrieciu, Monica; Mercuţ, Veronica; Popescu, Sanda Mihaela; Tǎrâţǎ, Daniela; Osiac, Eugen

    2018-03-01

    The study purpose is to highlight dental hard tissues changes of a tooth with dental wear as a consequence of excessive occlusal forces, using OCT. Methods: a central incisor extracted for periodontal reason was cleaned and it was embedded in a black acrylic resin block. The block was sectioned along the longitudinal axis of the tooth and prepared for OCT analysis. Results: The OCT signal showed differences between the labial and palatal dental hard tissue structures, even in areas without excessive occlusal solicitations. Conclusion: The OCT signal highlights changes of dental hard tissues structures according to excessive occlusal solicitations areas.

  12. Occlusion therapy of unilateral amblyopia with botulinum toxin induced ptosis.

    PubMed

    Halkiadakis, Ioannis; Iliaki, Olga; Kalyvianaki, Maria I; Tsilimbaris, Miltiadis K

    2007-01-01

    In order to evaluate the role of botulinum toxin induced ptosis as an occlusion method to treat unilateral deep strabismic amblyopia in two uncooperative children, we injected 0.2 ml of diluted botulinum toxin in the levator palpaebrae; low sedation was necessary in one of the two children. In both cases a marked ptosis was achieved, which lasted about four weeks and then gradually resolved completely. The visual acuity of the ablyopic eye increased in both children, making patching easy thereafter. One child developed amblyopia in the injected eye, which was handled successfully using part-time occlusion. No other side effects were noted. Whether this new method could be a simple, safe and effective alternative method of occlusion for the treatment of deep amblyopia in uncooperative children needs to be proven with a larger series of children.

  13. Steroid hormone and epidermal growth factor receptors in meningiomas.

    PubMed

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  14. Optimal occlusion uniformly partitions red blood cells fluxes within a microvascular network

    PubMed Central

    Tu, Shenyinying; Liu, Yu-Hsiu; Savage, Van M.; Hsiai, Tzung K.; Roper, Marcus

    2017-01-01

    In animals, gas exchange between blood and tissues occurs in narrow vessels, whose diameter is comparable to that of a red blood cell. Red blood cells must deform to squeeze through these narrow vessels, transiently blocking or occluding the vessels they pass through. Although the dynamics of vessel occlusion have been studied extensively, it remains an open question why microvessels need to be so narrow. We study occlusive dynamics within a model microvascular network: the embryonic zebrafish trunk. We show that pressure feedbacks created when red blood cells enter the finest vessels of the trunk act together to uniformly partition red blood cells through the microvasculature. Using mathematical models as well as direct observation, we show that these occlusive feedbacks are tuned throughout the trunk network to prevent the vessels closest to the heart from short-circuiting the network. Thus occlusion is linked with another open question of microvascular function: how are red blood cells delivered at the same rate to each micro-vessel? Our analysis shows that tuning of occlusive feedbacks increase the total dissipation within the network by a factor of 11, showing that uniformity of flows rather than minimization of transport costs may be prioritized by the microvascular network. PMID:29244812

  15. p63 regulates glutaminase 2 expression

    PubMed Central

    Giacobbe, Arianna; Bongiorno-Borbone, Lucilla; Bernassola, Francesca; Terrinoni, Alessandro; Markert, Elke Katrin; Levine, Arnold J.; Feng, Zhaohui; Agostini, Massimilano; Zolla, Lello; Agrò, Alessandro Finazzi; Notterman, Daniel A.; Melino, Gerry; Peschiaroli, Angelo

    2013-01-01

    The transcription factor p63 is critical for many biological processes, including development and maintenance of epidermal tissues and tumorigenesis. Here, we report that the TAp63 isoforms regulate cell metabolism through the induction of the mitochondrial glutaminase 2 (GLS2) gene both in primary cells and tumor cell lines. By ChIP analysis and luciferase assay, we confirmed that TAp63 binds directly to the p53/p63 consensus DNA binding sequence within the GLS2 promoter region. Given the critical role of p63 in epidermal differentiation, we have investigated the regulation of GLS2 expression during this process. GLS2 and TAp63 expression increases during the in vitro differentiation of primary human keratinocytes, and depletion of GLS2 inhibits skin differentiation both at molecular and cellular levels. We found that GLS2 and TAp63 expression are concomitantly induced in cancer cells exposed to oxidative stresses. siRNA-mediated depletion of GLS2 sensitizes cells to ROS-induced apoptosis, suggesting that the TAp63/GLS2 axis can be functionally important as a cellular antioxidant pathway in the absence of p53. Accordingly, we found that GLS2 is upregulated in colon adenocarcinoma. Altogether, our findings demonstrate that GLS2 is a bona fide TAp63 target gene, and that the TAp63-dependent regulation of GLS2 is important for both physiological and pathological processes. PMID:23574722

  16. Occlusal stabilization splint therapy in orofacial pain and tension-type headache.

    PubMed

    Kostrzewa-Janicka, J; Mierzwinska-Nastalska, E; Rolski, D; Szczyrek, P

    2013-01-01

    Studies suggest an association between orofacial pain, accompanying temporomandibular disorders of myogenous origin, and headache, especially its tension-type. The occlusal appliance therapy is one of the options for the treatment of orofacial pain due to masticatory muscles tenderness. The aim of the present study was to assess the effectiveness of occlusal stabilization splint therapy in myofascial pain and tension-type headache in patients with sleep-disordered breathing. Forty three such patients were enrolled into the study group. The patients were treated with stabilization occlusal splint of vertical thickness at vertical jaw separation, established individually for each patient using a cephalometric analysis. The intensity of orofacial pain (numeric rating scale) and headache (analog rating scale), frequency of headache (%), and jaw qualitative function were assessed at baseline and after 2 and 6 months. Medians of headache and orofacial pain intensity were reduced after 6 months of treatment compared with baseline: 6.0 vs. 2.0 (p < 0.0001) and 6.0 vs. 1.0 (p < 0.0001), respectively. Pain decreased below 3 score points in 61.8 % of the patients with headache (p = 0.23) and in 85.3 % of patients with orofacial pain (p < 0.0001). Overall, the improvement in both signs and symptoms of orofacial pain was observed 81.4 % of patients after using occlusal stabilization splint for 6 months. We conclude that occlusal stabilization splint was effective in reducing painful symptoms of temporomandibular disorders of myogenous origin, a frequent feature of sleep disordered breathing.

  17. Large arterial occlusive strokes as a medical emergency: need to accurately predict clot location.

    PubMed

    Vanacker, Peter; Faouzi, Mohamed; Eskandari, Ashraf; Maeder, Philippe; Meuli, Reto; Michel, Patrik

    2017-10-01

    Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently shown to be effective. Timely knowledge of the presence, site, and extent of arterial occlusions in the ischemic territory has the potential to influence patient selection for endovascular treatment. We aimed to find predictors of large vessel occlusive strokes, on the basis of available demographic, clinical, radiological, and laboratory data in the emergency setting. Patients enrolled in ASTRAL registry with acute ischemic stroke and computed tomography (CT)-angiography within 12 h of stroke onset were selected and categorized according to occlusion site. Easily accessible variables were used in a multivariate analysis. Of 1645 patients enrolled, a significant proportion (46.2%) had a large vessel occlusion in the ischemic territory. The main clinical predictors of any arterial occlusion were in-hospital stroke [odd ratios (OR) 2.1, 95% confidence interval 1.4-3.1], higher initial National Institute of Health Stroke Scale (OR 1.1, 1.1-1.2), presence of visual field defects (OR 1.9, 1.3-2.6), dysarthria (OR 1.4, 1.0-1.9), or hemineglect (OR 2.0, 1.4-2.8) at admission and atrial fibrillation (OR 1.7, 1.2-2.3). Further, the following radiological predictors were identified: time-to-imaging (OR 0.9, 0.9-1.0), early ischemic changes (OR 2.3, 1.7-3.2), and silent lesions on CT (OR 0.7, 0.5-1.0). The area under curve for this analysis was 0.85. Looking at different occlusion sites, National Institute of Health Stroke Scale and early ischemic changes on CT were independent predictors in all subgroups. Neurological deficits, stroke risk factors, and CT findings accurately identify acute ischemic stroke patients at risk of symptomatic vessel occlusion. Predicting the presence of these occlusions may impact emergency stroke care in regions with limited access to noninvasive vascular imaging.

  18. A mitosis block links active cell cycle with human epidermal differentiation and results in endoreplication.

    PubMed

    Zanet, Jennifer; Freije, Ana; Ruiz, María; Coulon, Vincent; Sanz, J Ramón; Chiesa, Jean; Gandarillas, Alberto

    2010-12-20

    How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation.

  19. A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

    PubMed Central

    Zanet, Jennifer; Freije, Ana; Ruiz, María; Coulon, Vincent; Sanz, J. Ramón; Chiesa, Jean; Gandarillas, Alberto

    2010-01-01

    How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation. PMID:21187932

  20. Potent endogenous allelopathic compounds in Lepidium sativum seed exudate: effects on epidermal cell growth in Amaranthus caudatus seedlings.

    PubMed

    Iqbal, Amjad; Fry, Stephen C

    2012-04-01

    Many plants exude allelochemicals--compounds that affect the growth of neighbouring plants. This study reports further studies of the reported effect of cress (Lepidium sativum) seed(ling) exudates on seedling growth in Amaranthus caudatus and Lactuca sativa. In the presence of live cress seedlings, both species grew longer hypocotyls and shorter roots than cress-free controls. The effects of cress seedlings were allelopathic and not due to competition for resources. Amaranthus seedlings grown in the presence of cress allelochemical(s) had longer, thinner hypocotyls and shorter, thicker roots--effects previously attributed to lepidimoide. The active principle was more abundant in cress seed exudate than in seedling (root) exudates. It was present in non-imbibed seeds and releasable from heat-killed seeds. Release from live seeds was biphasic, starting rapidly but then continuing gradually for 24 h. The active principle was generated by aseptic cress tissue and was not a microbial digestion product or seed-treatment chemical. Crude seed exudate affected hypocotyl and root growth at ~25 and ~450 μg ml(-1) respectively. The exudate slightly (28%) increased epidermal cell number along the length of the Amaranthus hypocotyl but increased total hypocotyl elongation by 129%; it resulted in a 26% smaller hypocotyl circumference but a 55% greater epidermal cell number counted round the circumference. Therefore, the effect of the allelochemical(s) on organ morphology was imposed primarily by regulation of cell expansion, not cell division. It is concluded that cress seeds exude endogenous substances, probably including lepidimoide, that principally regulate cell expansion in receiver plants.