Sample records for major epidermal survival

  1. Epidermal Growth Factor Receptor Cell Survival Signaling Requires Phosphatidylcholine Biosynthesis

    Matt Crook


    Full Text Available Identification of pro-cell survival signaling pathways has implications for cancer, cardiovascular, and neurodegenerative disease. We show that the Caenorhabditis elegans epidermal growth factor receptor LET-23 (LET-23 EGFR has a prosurvival function in counteracting excitotoxicity, and we identify novel molecular players required for this prosurvival signaling. uv1 sensory cells in the C. elegans uterus undergo excitotoxic death in response to activation of the OSM-9/OCR-4 TRPV channel by the endogenous agonist nicotinamide. Activation of LET-23 EGFR can effectively prevent this excitotoxic death. We investigate the roles of signaling pathways known to act downstream of LET-23 EGFR in C. elegans and find that the LET-60 Ras/MAPK pathway, but not the IP3 receptor pathway, is required for efficient LET-23 EGFR activity in its prosurvival function. However, activation of LET-60 Ras/MAPK pathway does not appear to be sufficient to fully mimic LET-23 EGFR activity. We screen for genes that are required for EGFR prosurvival function and uncover a role for phosphatidylcholine biosynthetic enzymes in EGFR prosurvival function. Finally, we show that exogenous application of phosphatidylcholine is sufficient to prevent some deaths in this excitotoxicity model. Our work implicates regulation of lipid synthesis downstream of EGFR in cell survival and death decisions.

  2. FasL and TRAIL Induce Epidermal Apoptosis and Skin Ulceration Upon Exposure to Leishmania major

    Eidsmo, Liv; Fluur, Caroline; Rethi, Bence; Eriksson Ygberg, Sofia; Ruffin, Nicolas; De Milito, Angelo; Akuffo, Hannah; Chiodi, Francesca


    Receptor-mediated apoptosis is proposed as an important regulator of keratinocyte homeostasis in human epidermis. We have previously reported that Fas/FasL interactions in epidermis are altered during cutaneous leishmaniasis (CL) and that keratinocyte death through apoptosis may play a pathogenic role for skin ulceration. To further investigate the alterations of apoptosis during CL, a keratinocyte cell line (HaCaT) and primary human epidermal keratinocytes were incubated with supernatants from Leishmania major-infected peripheral blood mononuclear cells. An apoptosis-specific microarray was used to assess mRNA expression in HaCaT cells exposed to supernatants derived from L. major-infected cultures. Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression were significantly up-regulated, and apoptosis was detected in both HaCaT and human epidermal keratinocyte cells. The keratinocyte apoptosis was partly inhibited through blocking of Fas or FasL and even more efficiently through TRAIL neutralization. Up-regulation of Fas on keratinocytes in epidermis and the presence of FasL-expressing macrophages and T cells in dermis were previously reported by us. In this study, keratinocytes expressing TRAIL, as well as the proapoptotic receptor TRAIL-R2, were detected in skin biopsies from CL cases. We propose that activation of Fas and TRAIL apoptosis pathways, in the presence of inflammatory mediators at the site of infection, leads to tissue destruction and ulceration during CL. PMID:17200196

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

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


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

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

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


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

  5. Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation.

    Erdogan, Bulent; Kodaz, Hilmi; Karabulut, Senem; Cinkaya, Ahmet; Tozkir, Hilmi; Tanriverdi, Ozgur; Cabuk, Devrim; Hacioglu, Muhammed Bekir; Turkmen, Esma; Hacibekiroglu, Ilhan; Uzunoglu, Sernaz; Cicin, Irfan


    Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01).The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.

  6. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis

    List, Karin; Haudenschild, Christian C; Szabo, Roman


    development and neoplasia. Matriptase/MT-SP1-deficient mice developed to term but uniformly died within 48 h of birth. All epidermal surfaces of newborn mice were grossly abnormal with a dry, red, shiny, and wrinkled appearance. Matriptase/MT-SP1-deficiency caused striking malformations of the stratum corneum...

  7. Simultaneous blockade of the epidermal growth factor receptor/mammalian target of rapamycin pathway by epidermal growth factor receptor inhibitors and rapamycin results in reduced cell growth and survival in biliary tract cancer cells.

    Herberger, Beata; Berger, Walter; Puhalla, Harald; Schmid, Katharina; Novak, Sabine; Brandstetter, Anita; Pirker, Christine; Gruenberger, Thomas; Filipits, Martin


    The prognosis of patients with biliary tract adenocarcinomas (BTA) is still poor due to lack of effective systemic treatment options. Knowledge of the molecular mechanisms involved in the pathogenesis of this disease is of importance for the development of new treatment strategies. We determined the expression of epidermal growth factor receptor (EGFR) and activated mammalian target of rapamycin (p-mTOR) in paraffin-embedded surgical specimens of BTA (n = 89) by immunohistochemistry. Overall survival was analyzed with Cox models adjusted for clinical and pathologic factors. Combined EGFR/p-mTOR expression was significantly associated with relapse-free survival [adjusted hazard ratio for relapse, 2.20; 95% confidence interval (95% CI), 1.45-3.33; P BTA cell lines was tested in short-term 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and long-term colony formation assays. Simultaneous blockade of EGFR and mTOR in biliary tract cancer cell lines results in a synergistic inhibition of both phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways, leading to reduced cell growth and survival. These results suggest that combined targeted therapy with EGFR and mTOR inhibitors may potentially benefit patients with BTAs and should be further evaluated in clinical trials.

  8. Impact of the epidermal growth factor receptor mutation status on the post-recurrence survival of patients with surgically resected non-small-cell lung cancer.

    Takenaka, Tomoyoshi; Takenoyama, Mitsuhiro; Yamaguchi, Masafumi; Toyozawa, Ryo; Inamasu, Eiko; Kojo, Miyako; Toyokawa, Gouji; Yoshida, Tsukihisa; Shiraishi, Yoshimasa; Morodomi, Yosuke; Hirai, Fumihiko; Taguchi, Kenichi; Shimokawa, Mototsugu; Seto, Takashi; Ichinose, Yukito


    The impact of epidermal growth factor receptor (EGFR) status and the use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy have not been well discussed only in recurrent non-small-cell lung cancer (NSCLC). The purpose of this study was to identify the prognostic factors associated with post-recurrence survival after surgical resection of NSCLC in terms of the EGFR mutation status and the use of EGFR-TKI therapy. From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of these patients, 280 experienced postoperative recurrence by the end of 2012. We reviewed the cases of recurrence and analysed the predictors and length of post-recurrence survival. The median post-recurrence survival time and the 5-year survival rate of all patients were 25 months and 20.8%, respectively. A multivariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (PS), brain metastasis, number of sites of recurrence and EGFR mutation status to be independent prognostic factors for post-recurrence survival. Among all cases, the median post-recurrence survival time according to the use of EGFR-TKI therapy was as follows: 49 months in the EGFR mutation-positive patients treated with EGFR-TKI therapy, 20 months in the EGFR wild or unknown cases treated with EGFR-TKI therapy and 17 months in the patients not treated with EGFR-TKI therapy. As to EGFR mutation-positive cases, the patients treated with EGFR-TKIs exhibited significantly longer post-recurrence survival time than the patients treated without EGFR-TKIs (49 vs 12 months). It is essential for recurrent NSCLC patients to be examined for the EGFR mutation status. Patients with a positive EGFR mutation status receive significant benefits from EGFR-TKI therapy. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. Do phosphatase of regenerating liver-3, matrix metalloproteinases-2, matrix metalloproteinases-9, and epidermal growth factor receptor-1 predict response to therapy and survival in glioblastoma multiforme?

    Priyanka Soni


    Full Text Available Context: Poor survival of the glioblastoma multiforme (GBM has been attributed in part to the invasive nature of the lesion making complete surgical removal near impossible. Phosphatase of regenerating liver-3 (PRL-3, matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9, and epidermal growth factor receptor (EGFR-1 play a role in invasive nature of tumor cells. Aims: This study was conducted to evaluate PRL-3, MMP-2, MMP-9, and EGFR-1 (markers expression in cases to GBM and to correlate their expression with therapy response and survival. Settings and Design: GBM cases (n = 62 underwent surgery followed by radiation (n = 34 and chemoradiation (n = 28. Using WHO Response Evaluation Criteria in Solid Tumors criteria response to therapy was assessed at 3 months and cases followed up for survival. Subjects and Methods: Expression of markers was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots. Statistical Analysis Used: Kaplan–Meier, ANOVA, Chi-square test, univariate, and multivariate Cox-regression analysis was done. Results: Response to therapy was evident in 54.8% cases of responders with the mean survival of 494.03 ± 201.13 days and 45.2% cases of non responders (278.32 ± 121.66 days with P = 0.001. Mean survival for the patient's opted chemoradiation was 457.43 ± 222.48 days which was approximately 3 months greater than those who opted radiation alone (P = 0.029. We found PRL-3 overexpression was an independent, significant, poor prognostic factor for survival by multivariate analysis (P = 0.044. Cases negative for MMP's and EGFR showed increased survival, but the difference was insignificant. Conclusion: PRL-3 expression appears to be related to an adverse disease outcome.

  10. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells

    Keith A. Cengel


    Full Text Available Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor o was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFRactivated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  11. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells1

    Cengel, Keith A.; Voong, K. Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B.; Stanbridge, Eric; Kao, Gary D.; McKenna, W. Gillies; Bernhard, Eric J.


    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor α was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers. PMID:17460778

  12. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

    Cengel, Keith A; Voong, K Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B; Stanbridge, Eric; Kao, Gary D; McKenna, W Gillies; Bernhard, Eric J


    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor alpha was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  13. Survival Analysis and its Associated Factors of Beta Thalassemia Major in Hamadan Province

    Reza Zamani


    Full Text Available Background: There currently is a lack of knowledge about the long-term survival of patients with beta thalassemia (BT, particularly in regions with low incidence of the disease. The aim of the present study was to determine the survival rate of the patients with BT major and the factors associated with the survival time. Methods: This retrospective cohort study was performed in Hamadan province, located in the west of Iran. The study included patients that referred to the provincial hospitals during 16 year period from 1997 to 2013. The follow up of each subject was calculated from the date of birth to the date of death. Demographic and clinical data were extracted from patients’ medical records using a checklist. Statistical analysis included the Kaplan-Meier method to analyze survivals, log-rank to compare curves between groups, and Cox regression for multivariate prognostic analysis. Results: A total of 133 patients with BT major were enrolled, 54.9% of whom were male and 66.2% were urban. The 10-, 20- and 30-year survival rate for all patients were 98.3%, 88.4% and 80.5%, respectively. Based on hazard ratio (HR, we found that accompanied diseases (P=0.01, blood type (P=0.03 and residency status (P=0.01 were significant predictors for the survival time of patients. Conclusion: The survival rate of BT patients has improved. Future researches such as prospective designs are required for the estimation of survival rate and to find other prognostic factors, which have reliable sources of data.

  14. Effect of PIT tags on the survival and recruitment of Great Tits Parus major

    Nicolaus, Marion; Bouwman, Karen M.; Dingemanse, Niels J.


    We describe the use of subcutaneous passive integrated transponder (PIT) tags in nestling and adult Great Tits Parus major. We investigated whether subcutaneous PIT tags affected fledging success, winter condition, survival and/or recruitment. We found no negative effects of PIT tags on any of these

  15. Major vault protein supports glioblastoma survival and migration by upregulating the EGFR/PI3K signalling axis.

    Lötsch, Daniela; Steiner, Elisabeth; Holzmann, Klaus; Spiegl-Kreinecker, Sabine; Pirker, Christine; Hlavaty, Juraj; Petznek, Helga; Hegedus, Balazs; Garay, Tamas; Mohr, Thomas; Sommergruber, Wolfgang; Grusch, Michael; Berger, Walter


    Despite their ubiquitous expression and high conservation during evolution, precise cellular functions of vault ribonucleoparticles, mainly built of multiple major vault protein (MVP) copies, are still enigmatic. With regard to cancer, vaults were shown to be upregulated during drug resistance development as well as malignant transformation and progression. Such in a previous study we demonstrated that human astrocytic brain tumours including glioblastoma are generally high in vault levels while MVP expression in normal brain is comparably low. However a direct contribution to the malignant phenotype in general and that of glioblastoma in particular has not been established so far. Thus we address the questions whether MVP itself has a pro-tumorigenic function in glioblastoma. Based on a large tissue collection, we re-confirm strong MVP expression in gliomas as compared to healthy brain. Further, the impact of MVP on human glioblastoma aggressiveness was analysed by using gene transfection, siRNA knock-down and dominant-negative genetic approaches. Our results demonstrate that MVP/vaults significantly support migratory and invasive competence as well as starvation resistance of glioma cells in vitro and in vivo. The enhanced aggressiveness was based on MVP-mediated stabilization of the epidermal growth factor receptor (EGFR)/phosphatidyl-inositol-3-kinase (PI3K) signalling axis. Consequently, MVP overexpression resulted in enhanced growth and brain invasion in human glioblastoma xenograft models. Our study demonstrates, for the first time, that vaults have a tumour-promoting potential by stabilizing EGFR/PI3K-mediated migration and survival pathways in human glioblastoma.

  16. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab



    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer. PMID:26623060

  17. Leishmania major: disruption of signal peptidase type I and its consequences on survival, growth and infectivity.

    Taheri, Tahereh; Salmanian, Ali-Hatef; Gholami, Elham; Doustdari, Fatemeh; Zahedifard, Farnaz; Rafati, Sima


    Leishmania major (L. major) signal peptidase type I (SPase I) is an endopeptidase encoded by a single-copy gene. In all organisms, SPase I is responsible for removing the signal peptide from secretory pre-proteins and releasing mature proteins to cellular or extra-cellular space. In this study, the role of SPase I in L. major is investigated by gene deletion using homologous recombination (HR). The null mutant of SPase I was not possible to create, suggesting that SPase I is an essential gene for parasite survival. The obtained heterozygote mutant by disrupting one allele of SPase I in L. major showed significantly reduced level of infectivity in bone marrow-derived macrophages. In addition, the heterozygote mutants are unable to cause cutaneous lesion in susceptible BALB/c mice. This is the first report showing that SPase I may have an important role in Leishmania infectivity, e.g. in differentiation and survival of amastigotes. Apparently, the SPase I expression is not essential for in vitro growth of the parasite.

  18. Effect of the major glycosides of Harpagophytum procumbens (Devil's Claw) on epidermal cyclooxygenase-2 (COX-2) in vitro.

    Abdelouahab, Nassima; Heard, Charles


    Harpagophytum procumbens, commonly known as Devil's Claw, is indigenous to southern Africa, and extracts of the tubers have been used for centuries in the treatment of a variety of inflammatory disorders. Its major active components, harpagoside (1), harpagide (2), 8-coumaroylharpagide (3), and verbascoside (4), are believed to interact either synergistically or antagonistically in modulating the enzymes responsible for inducing inflammation, although this has not been probed hitherto. In the current work, the ability of these compounds to inhibit the expression of COX-2 following administration to freshly excised porcine skin has been investigated. An ethanol-soluble extract of H. procumbens tubers and two of the pure compounds tested showed promising activity in Western blotting and immunocytochemical assays, with harpagoside (1) and 8-coumaroylharpagide (3) exhibiting greater reductions in COX-2 expression than verbascoside (4). Harpagide (2) caused a significant increase in the levels of COX-2 expression after 6 h of topical application. The data suggest that the efficacy of H. procumbens is dependent upon the ratios of compounds 1-4 present, which is inconsistent with some current official monograph specifications based solely on harpagoside (1) content.

  19. Survival of diabetes patients with major amputation is comparable to malignant disease.

    Hoffmann, Martin; Kujath, Peter; Flemming, Annette; Proß, Moritz; Begum, Nehara; Zimmermann, Markus; Keck, Tobias; Kleemann, Markus; Schloericke, Erik


    Almost all studies on diabetic foot syndrome focused on prevention of amputation and did not investigate long-term prognosis and survival of patients as a primary outcome parameter. We did a retrospective cohort study including 314 patients who had diabetic foot syndrome and underwent amputation between December 1995 and January 2001. A total of 48% of patients received minor amputation (group I), 15% only major amputation (group II) and 36% initially underwent a minor amputation that was followed by a major amputation (group III). Statistically significant differences were observed in comparison of the median survival of group I to group II (51 vs. 40 months; p = 0.016) and of group II to group III (40 vs. 55 months; p = 0.003). The prognosis of patients with major amputation due to diabetic foot syndrome is comparable to patients with malignant diseases. Vascular interventions did not improve the individual prognosis of patients. © The Author(s) 2015.

  20. Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival.

    Jeon, Ye Won; Kang, Su Hwan; Park, Min Ho; Lim, Woosung; Cho, Se Heun; Suh, Young Jin


    The association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined. We analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox's proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories. A U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals. We observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules.

  1. Epidermal nevus syndromes.

    Asch, Sarah; Sugarman, Jeffrey L


    The term epidermal nevus syndrome (ENS) has been used to describe the association of epidermal hamartomas and extracutaneous abnormalities. Although many continue to use the term "ENS," it is now understood that this is not one disease, but rather a heterogeneous group with distinct genetic profiles defined by a common cutaneous phenotype: the presence of epidermal and adnexal hamartomas that are associated with other organ system involvement. One commonality is that epidermal nevi often follow the lines of Blaschko and it appears the more widespread the cutaneous manifestations, the greater the risk for extracutaneous manifestations. The majority of the extracutaneous manifestations involve the brain, eye, and skeletal systems. The CNS involvement is wide ranging and involves both clinical manifestations such as intellectual disability and seizures, as well as structural anomalies. Several subsets of ENS with characteristic features have been delineated including the nevus sebaceus syndrome, Proteus syndrome, CHILD syndrome, Becker's nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica. Advances in molecular biology have revealed that the manifestations of ENS are due to genomic mosaicism. It is likely that the varied clinical manifestations of ENS are due in great part to the functional effects of specific genetic defects. Optimal management of the patient with ENS involves an interdisciplinary approach given the potential for multisystem involvement. Of note, epidermal nevi have been associated with both benign and malignant neoplasms, and thus ongoing clinical follow-up is required.

  2. Does prehospital time affect survival of major trauma patients where there is no prehospital care?

    S B Dharap


    Full Text Available Background: Survival after major trauma is considered to be time dependent. Efficient prehospital care with rapid transport is the norm in developed countries, which is not available in many lower middle and low-income countries. The aim of this study was to assess the effect of prehospital time and primary treatment given on survival of major trauma patients in a setting without prehospital care. Materials and Methods: This prospective observational study was carried out in a university hospital in Mumbai, from January to December 2014. The hospital has a trauma service but no organized prehospital care or defined interhospital transfer protocols. All patients with life- and/or limb-threatening injuries were included in the study. Injury time and arrival time were noted and the interval was defined as “prehospital time” for the directly arriving patients and as “time to tertiary care” for those transferred. Primary outcome measure was in-hospital death (or discharge. Results: Of 1181 patients, 352 were admitted directly from the trauma scene and 829 were transferred from other hospitals. In-hospital mortality was associated with age, mechanism and mode of injury, shock, Glasgow Coma Score <9, Injury Severity Score ≥16, need for intubation, and ventilatory support on arrival; but neither with prehospital time nor with time to tertiary care. Transferred patients had a significantly higher mortality (odds ratio = 1.869, 95% confidence interval = 1.233–2.561, P = 0.005 despite fewer patients with severe injury. Two hundred and ninety-four (35% of these needed airway intervention while 108 (13% needed chest tube insertion on arrival to the trauma unit suggesting inadequate care at primary facility. Conclusion: Mortality is not associated with prehospital time but with transfers from primary care; probably due to deficient care. To improve survival after major trauma, enhancement of resources for resuscitation and capacity building of on

  3. Expression of epidermal growth factor receptor (EGFR) and activated EGFR predict poor response to (chemo)radiation and survival in cervical cancer

    Noordhuis, M.G.; Eijsink, J.J.H.; ten Hoor, K.A.; Roossink, F.; Hollema, H.; Arts, H.J.G.; Pras, Elisabeth; Maduro, John; Reyners, A.K.L.; de Bock, G.H.; Wisman, G.B.A.; Schuuring, E.; van der Zee, A.G.J.


    PURPOSE: Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of t

  4. Determinants of survival and major amputation after peripheral endovascular intervention for critical limb ischemia

    Vierthaler, Luke; Callas, Peter W.; Goodney, Philip P.; Schanzer, Andres; Patel, Virenda I.; Cronenwett, Jack; Bertges, Daniel J.


    Objective Our objective was to analyze periprocedural and 1-year outcomes of peripheral endovascular intervention (PVI) for critical limb ischemia (CLI). Methods We reviewed 1244 patients undergoing 1414 PVIs for CLI (rest pain, 29%; tissue loss, 71%) within the Vascular Study Group of New England (VSGNE) from January 2010 to December 2011. Overall survival (OS), amputation-free survival (AFS), and freedom from major amputation at 1 year were analyzed using the Kaplan-Meier method. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The number of arteries treated during each procedure were 1 (49%), 2 (35%), 3 (12%), and ≥4 (5%). Target arterial segments and TransAtlantic Inter-Society Consensus classifications were aortoiliac, 27% (A, 48%; B, 28%; C, 12%; and D, 12%); femoral-popliteal, 48% (A, 29%; B, 34%; C, 20%; and D, 17%); and infrapopliteal, 25% (A, 17%; B, 14%; C, 25%; D, 44%). Technical success was 92%. Complications included access site hematoma (5.0%), occlusion (0.3%), and distal embolization (2.4%). Mortality and major amputation rates were 2.8% and 2.2% at 30 days, respectively. Overall percutaneous or open reintervention rate was 8.0% during the first year. At 1-year, OS, AFS, and freedom from major amputation were 87%, 87%, and 94% for patients with rest pain and 80%, 71%, and 81% for patients with tissue loss. Independent predictors of reduced 1-year OS (C index = .74) included dialysis (HR, 3.8; 95% CI, 2.8–5.1; P 80 years (HR, 2.2; 95% CI, 1.7–2.8; P 1.8 mg/dL (HR, 1.9; 95% CI, 1.3–2.8; P PVI for CLI are associated with different patient characteristics. Dialysis dependence is a common predictor that portends especially poor outcomes. These data may facilitate efforts to improve patient selection and, after further validation, enable risk-adjusted outcome reporting for CLI patients undergoing PVI. (J Vasc Surg 2015;62:655–64.) PMID:26215708

  5. Letter to the Editor concerning the article "Long term complications of Stevens-Johnson syndrome/Toxic epidermal necrolysis: The spectrum of chronic problems in patients who survive an episode of SJS/TEN necessitates multi-disciplinary follow up.

    Olteanu, C; Dodiuk-Gad, R; Hashimoto, R; Shear, N


    We read with great interest, the review paper by Lee et al. on the long term complications of Stevens-Johnson syndrome and toxic epidermal necrolysis. We would like to congratulate the authors on this important and excellent overview. This review demonstrated that SJS/TEN has a severe, chronic phase with major physical morbidities. We wish to raise awareness to the major emotional complications among survivors; as was found in our study published in the British Journal of Dermatology by Dodiuk-Gad et al. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Survival

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  7. Survival and major neurodevelopmental impairment in extremely low gestational age newborns born 1990–2000: a retrospective cohort study

    deRegnier Raye-Ann


    Full Text Available Abstract Background It is important to determine if rates of survival and major neurodevelopmental impairment in extremely low gestational age newborns (ELGANs; infants born at 23–27 weeks gestation are changing over time. Methods Study infants were born at 23 to 27 weeks of gestation without congenital anomalies at a tertiary medical center between July 1, 1990 and June 30, 2000, to mothers residing in a thirteen-county region in North Carolina. Outcomes at one year adjusted age were compared for two epochs of birth: epoch 1, July 1, 1990 to June 30, 1995; epoch 2, July 1, 1995 to June 30, 2000. Major neurodevelopmental impairment was defined as cerebral palsy, Bayley Scales of Infant Development Mental Developmental Index more than two standard deviations below the mean, or blindness. Results Survival of ELGANs, as a percentage of live births, was 67% [95% confidence interval: (61, 72] in epoch 1 and 71% (65, 75 in epoch 2. Major neurodevelopmental impairment was present in 20% (15, 27 of survivors in epoch 1 and 14% (10, 20 in epoch 2. When adjusted for gestational age, survival increased [odds ratio 1.5 (1.0, 2.2, p = .03] and major neurodevelopmental impairment decreased [odds ratio 0.54 (0.31, 0.93, p = .02] from epoch 1 to epoch 2. Conclusion The probability of survival increased while that of major neurodevelopmental impairment decreased during the 1990's in this regionally based sample of ELGANs.

  8. A recipe for postfledging survival in great tits Parus major: be large and be early (but not too much).

    Rodríguez, Samuel; van Noordwijk, Arie J; Álvarez, Elena; Barba, Emilio


    Survival of juveniles during the postfledging period can be markedly low, which may have major consequences on avian population dynamics. Knowing which factors operating during the nesting phase affect postfledging survival is crucial to understand avian breeding strategies. We aimed to obtain a robust set of predictors of postfledging local survival using the great tit (Parus major) as a model species. We used mark-recapture models to analyze the effect of hatching date, temperatures experienced during the nestling period, fledging size and body mass on first-year postfledging survival probability of great tit juveniles. We used data from 5192 nestlings of first clutches ringed between 1993 and 2010. Mean first-year postfledging survival probability was 15.2%, and it was lower for smaller individuals, as well as for those born in either very early or late broods. Our results stress the importance of choosing an optimum hatching period, and raising large chicks to increase first-year local survival probability in the studied population.

  9. Cognitive performance and functional status are the major factors predicting survival of centenarians in Poland.

    Mossakowska, Malgorzata; Broczek, Katarzyna; Wieczorowska-Tobis, Katarzyna; Klich-Rączka, Alicja; Jonas, Marta; Pawlik-Pachucka, Eliza; Safranow, Krzysztof; Kuznicki, Jacek; Puzianowska-Kuznicka, Monika


    Clinical and biochemical predictors of extreme longevity would be useful in geriatric practice but have still not been clearly defined. To identify the best nongenetic predictors of survival in centenarians, we examined 340 individuals aged 100+ years. A detailed questionnaire was completed, and comprehensive geriatric assessment and blood analyses were performed. Survival of study participants was checked annually over the period of 10 years. In the univariate Cox proportional hazards model, a longer survival of centenarians was correlated with a higher adjusted Mini-Mental State Examination (MMSE(adj)) score (p HR = 0.978 per each MMSE(adj) point, 95% CI: 0.964-0.993, p = .004; HR = 0.900 per each ADL point, 95% CI: 0.842-0.962, p = .002, respectively). In multivariate analysis with the ADL score substituted by the IADL(adj) score, the only predictor of survival was MMSE(adj) (HR = 0.973 per each MMSE(adj) point, 95% CI: 0.958-0.988, p = .0006). Cognitive and functional performances are predictors of survival in centenarians. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:

  10. Leishmania major survival in selective Phlebotomus papatasi sand fly vector requires a specific SCG-encoded lipophosphoglycan galactosylation pattern.

    Deborah E Dobson

    Full Text Available Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In "selective" sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG, which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG repeat units. For the "selective" fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both 'poly-scGal' and 'null-scGal' lines survived poorly relative to PpapJ-sympatric L. major FV1 and other 'mono-scGal' lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing 'null-scGal'-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a 'PpapJ-optimal' scGal-LPG PAMP. Unexpectedly, these "L. major FV1-cloaked" L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific 'mono-scGal' pattern. However, failure of 'mono-scGal' L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite

  11. Survival times of patients with a first hip fracture with and without subsequent major long-bone fractures.

    Angthong, Chayanin; Angthong, Wirana; Harnroongroj, Thos; Naito, Masatoshi; Harnroongroj, Thossart


    Survival rates are poorer after a second hip fracture than after a first hip fracture. Previous survival studies have included in-hospital mortality. Excluding in-hospital deaths from the analysis allows survival times to be evaluated in community-based patients. There is still a lack of data regarding the effects of subsequent fractures on survival times after hospital discharge following an initial hip fracture. This study compared the survival times of community-dwelling patients with hip fracture who had or did not have a subsequent major long-bone fracture. Hazard ratios and risk factors for subsequent fractures and mortality rates with and without subsequent fractures were calculated. Of 844 patients with hip fracture from 2000 through 2008, 71 had a subsequent major long-bone fracture and 773 did not. Patients who died of other causes, such as perioperative complications, during hospitalization were excluded. Such exclusion allowed us to determine the effect of subsequent fracture on the survival of community-dwelling individuals after hospital discharge or after the time of the fracture if they did not need hospitalization. Demographic data, causes of death, and mortality rates were recorded. Differences in mortality rates between the patient groups and hazard ratios were calculated. Mortality rates during the first year and from 1 to 5 years after the most recent fracture were 5.6% and 1.4%, respectively, in patients with subsequent fractures, and 4.7% and 1.4%, respectively, in patients without subsequent fractures. These rates did not differ significantly between the groups. Cox regression analysis and calculation of hazard ratios did not show significant differences between patients with subsequent fractures and those without. On univariate and multivariate analyses, age fracture. This study found that survival times did not differ significantly between patients with and without subsequent major long-bone fractures after hip fracture. Therefore, all

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

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


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

  13. Survival with Emergency Tourniquet Use to Stop Bleeding in Major Limb Trauma


    systolic blood pressures by McManus et al.23,24 Statistical Analysis Descriptive statistics were used for tourniquet applications and resulting outcomes...whereas the mean ISSs of the prehospital and ED groups were not statistically different (P 0.6). Survival Association When Shock Was Absent controversy. J Trauma. 2004;56:214–215. 18. Husum H, Ang SC, Fosse E. War Surgery Field Manual, Penang , Malaysia: Third World Network. 1995;85:145

  14. Anti-apoptotic BFL-1 is the major effector in activation-induced human mast cell survival.

    Maria Ekoff

    Full Text Available Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine. Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-X(L, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival.

  15. Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

    Bo Dai; Yun-Yi Kong; Ding-Wei Ye; Chun-Guang Ma; Xiao-Yan Zhou; Xu-Dong Yao


    Aim: To investigate human epidermal growth factor receptor type 2 (HER2) protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods: Immuno-histochemistry (IHC) was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transure- thral resection of the prostate (TURP). HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2+ were investigated for HER2 gene amplification status by fluorescent in situ hybridization (FISH). Results: Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1+, 2+ and 3+ in 49 (47.1%), 45 (43.3%), 8 (7.7%) and 2 (1.9%) cases, respectively. There was a significant association between HER2 expression and Gleason score (P = 0.026). HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores > 2+ showed HER2 gene amplification. Patients with HER2 scores ≥ 2+ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 (P = 0.004) and 1+ (P = 0.034). Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death (P = 0.039). Conclusion: An HER2 IHC score ≥ 2+ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

  16. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer.

    Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M; Busch, Theresa M; Cengel, Keith A


    Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT-mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT-mediated activation of EGFR were also observed in response to BPD-mediated PDT in multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and was observed to occur in response to porfimer sodium-mediated PDT. In addition, we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR association and that inhibiting STAT3 signaling prior to PDT leads to increased PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to increased PDT cytotoxicity through a mechanism that involves increased apoptotic cell death. Taken together, these results demonstrate that PDT stimulates the nuclear accumulation of both EGFR and STAT3 and that targeting these survival pathways is a potentially promising strategy that could be adapted for clinical trials of PDT for patients with serosal spread of malignancy.

  17. Verrucous epidermal nevus

    Kim, Randie; Marmon, Shoshana; Kaplan, Jennifer; Kamino, Hideko; Pomeranz, Miriam Keltz


    A 64-year-old man presented with a three-year history of an enlarging, pruritic, linear, verrucous plaque on his left lower extremity. Histopathologic examination was consistent with a verrucous epidermal nevus, which is a benign epidermal hamartoma, most commonly observed in the pediatric population. Verrucous epidermal nevi are often refractory to treatment and have high rates of recurrences, causing them to be therapeutic challenges. We review the treatment modalities reported to be effect...

  18. Lapatinib-associated mucocutaneous toxicities are clinical predictors of improved progression-free survival in patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer.

    Araki, Kazuhiro; Fukada, Ippei; Horii, Rie; Takahashi, Shunji; Akiyama, Futoshi; Iwase, Takuji; Ito, Yoshinori


    This study is aimed to identify clinical predictors, other than HER2 overexpression, for the response to lapatinib plus capecitabine (LAPCAP) in patients with HER2-positive advanced breast cancer (HER2ABC). Data from our medical records of 76 patients from June 2009 to March 2013 were analyzed. Evaluations of these patients with HER2ABC treated with LAPCAP included baseline characteristics, dose modifications, efficacy, and incidence of adverse events (AEs). With a median follow-up of 20 months, the median number of prior therapies for ABC before LAPCAP was 2 (range 0-13), and 66 patients had previously received trastuzumab. For LAPCAP, the overall response rate was 21 %, and the clinical benefit rate was 60 %. During the initial 12-month observation period, 93 % of patients had AEs. The most common AE was hand-foot syndrome (HFS) in 55 patients. Progression-free survival (PFS) was better in patients who had HFS than in those who did not (p = 0.0002). Since HFS is a well-known AE associated with CAP, whether CAP dose affected PFS or not was investigated, but no positive relationship was found. Since several studies with EGFR-targeted agents have suggested a positive correlation between cutaneous toxicities and outcomes, whether the incidence of any AEs affected PFS or not was explored among 76 patients. HFS, diarrhea, and rash were significant favorable factors (p = 0.0002, 0.0088, and 0.0011). The median PFS of patients who had all three AEs was 13.2 months, compared with 2.6 months for those who did not (p = 0.00000174). Mucocutaneous toxicities may be predictors of the response to LAP in patients with HER2ABC.

  19. The Event Chain of Survival in the Context of Music Festivals: A Framework for Improving Outcomes at Major Planned Events.

    Lund, Adam; Turris, Sheila


    Despite the best efforts of event producers and on-site medical teams, there are sometimes serious illnesses, life-threatening injuries, and fatalities related to music festival attendance. Producers, clinicians, and researchers are actively seeking ways to reduce the mortality and morbidity associated with these events. After analyzing the available literature on music festival health and safety, several major themes emerged. Principally, stakeholder groups planning in isolation from one another (ie, in silos) create fragmentation, gaps, and overlap in plans for major planned events (MPEs). The authors hypothesized that one approach to minimizing this fragmentation may be to create a framework to "connect the dots," or join together the many silos of professionals responsible for safety, security, health, and emergency planning at MPEs. Adapted from the well-established literature regarding the management of cardiac arrests, both in and out of hospital, the "chain of survival" concept is applied to the disparate groups providing services that support event safety in the context of music festivals. The authors propose this framework for describing, understanding, coordinating and planning around the integration of safety, security, health, and emergency service for events. The adapted Event Chain of Survival contains six interdependent links, including: (1) event producers; (2) police and security; (3) festival health; (4) on-site medical services; (5) ambulance services; and (6) off-site medical services. The authors argue that adapting and applying this framework in the context of MPEs in general, and music festivals specifically, has the potential to break down the current disconnected approach to event safety, security, health, and emergency planning. It offers a means of shifting the focus from a purely reactive stance to a more proactive, collaborative, and integrated approach. Improving health outcomes for music festival attendees, reducing gaps in planning

  20. Major clinical events, signs and severity assessment scores related to actual survival in patients who died from primary biliary cirrhosis. A long-term historical cohort study

    van Dam, GM; Gips, CH; Reisman, Y; Maas, KW; Purmer, IM; Huizenga, [No Value; Verbaan, BW


    BACKGROUND/AIMS: One of the prognostic methods for survival in primary biliary cirrhosis (PBC) is the Mayo model, with a time-scale limited to 7 years. The aim of our study was to assess how major clinical events, signs, several severity assessment methods and Mayo survival probabilities fit in with

  1. Genetics Home Reference: epidermal nevus

    ... thicker and darker and develop a wart-like (verrucous) appearance. Often, keratinocytic epidermal nevi follow a pattern ... are also known as linear epidermal nevi or verrucous epidermal nevi, based on characteristics of their appearance. ...

  2. Evolution of dinosaur epidermal structures.

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


    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. Toksisk epidermal nekrolyse

    Bygum, Anette; Andersen, Klaus Ejner


    Toxic epidermal necrolysis (TEN) is a rare, mostly drug-induced life-threatening mucocutaneous reaction with generalised symptoms and internal organ involvement. Current treatment strategy focuses on supportive intensive care with close collaboration among many specialties. Specific therapies...

  4. Long term complications of Stevens-Johnson syndrome / Toxic epidermal necrolysis: The spectrum of chronic problems in patients who survive an episode of SJS/TEN necessitates multi-disciplinary follow up.

    Lee, H Y; Walsh, S A; Creamer, D


    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse reactions to drugs which cause a life-threatening eruption of mucocutaneous blistering and epithelial sloughing. The two terms describe phenotypes occurring at either end of a severity spectrum: SJS is the less extensive form (TEN is the more extensive (>30% BSA detachment). Cases in which there is 10-30% epidermal detachment are referred to as SJS-TEN overlap. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. 自体全层皮肤移植成活过程中表皮干细胞的变化规律%Changing rule of epidermal stem cells in the survival of autologous full-thickness skin graft

    陶克奇; 李利平


    正常,皮片与创面粘连紧密,创面有部分毛根长出;术后14 d皮片创周已经和创面完全愈合;术后30 d皮片颜色较正常稍微深,毛发生长同正常皮肤.②苏木精-伊红染色病理切片观察结果:前4组见皮片内细胞水肿,有少量炎性细胞浸润,术后5 d发现皮片部分角质细胞坏死脱落.③阳性细胞的分布和数量变化规律:整合素β1和基因物质P63阳性细胞在术前主要分布于表皮的基底层和毛囊隆突部,从术后24 h阳性细胞开始在表皮的各层出现,且数量逐渐增多,术后14和21 d在表皮的各层均见到较多的阳性细胞,术后30 d阳性细胞主要分布在表皮的基底层,但在其它各层仍然有少量的阳性细胞出现.免疫组化切片中基因物质P63的阳性细胞数均高于同时限点β1整合素的阳性细胞数,从术后24 h开始减少,到术后3 d达到最低点,然后逐渐增加,到术后7 d阳性细胞的比例达到或接近术前,继续增加.术后21 d时阳性细胞比例达到最高点,然后又逐渐减低,术后30 d时阳性细胞比例仍高于术前.结论:①表皮干细胞在自体全层皮片移植成活过程中先减少,然后逐渐增加至超过正常皮肤.②自体全层皮肤移植成活过程中,表皮干细胞在皮肤中的排列紊乱,几乎在表皮各层均能见到表皮干细胞;而后又逐渐集中于表皮的基底层和毛囊隆突部.%BACKGROUND: Study on epidermal stem cells (ESCs) is satisfying. However, the amount and the distribution dynamic changing rule in each skin layer of ESCs during survival of skin graft need to be investigated.OBJECTIVE: To observe the changing rule of ESCs in the microenvironment during the survival of full-thickness skin graft.DESIGN: Prospective animal experiment based on controlled observation.SETTTNG: Department of Burn and Plastic Surgery, First Hospital Affiliated to Nanhua University.MATERIALS: Forty-two Wistar rats of clean grade and either gender, aged 2 to 3

  6. Perfil da incidência e da sobrevida de pacientes com carcinoma epidermóide oral em uma população brasileira Incidence and survival profile of patients with oral squamous cell carcinoma in a Brazilian population

    Lucinei Roberto de Oliveira


    Full Text Available INTRODUÇÃO: A incidência do câncer bucal no Brasil é uma das mais altas do mundo. OBJETIVOS: Avaliar o perfil, os fatores de risco e a sobrevida de pacientes diagnosticados com carcinoma epidermóide oral entre 1982 e 2002 em uma população brasileira. MATERIAL E MÉTODO: Idade, gênero, local da lesão, história pregressa, consumo de tabaco e bebidas alcoólicas, exposição actínica, traumatismo por prótese, recidivas, metástases e sobrevida foram obtidos dos prontuários. RESULTADOS: Dos 340 pacientes 84,4% eram homens e 15,6%, mulheres (5,4:1. As lesões linguais foram as mais freqüentes (27,9%. Vinte por cento dos pacientes relataram traumatismo por prótese e em 73,8% das lesões em lábio inferior foi relatada exposição actínica desprotegida. Não houve diferença entre as regiões anatômicas e o consumo de tabaco em relação a recidivas, metástases regionais e metástases à distância. O tempo médio de história pregressa foi de 13 meses, havendo diferença entre as regiões anatômicas. A sobrevida em cinco anos foi de 24%. A sobrevida dos pacientes com recidivas e/ou metástases variou conforme a idade analisada ( 60 anos, mas não houve diferença quanto à história pregressa e às regiões anatômicas. A discrepância homem/mulher encontrada foi alta, diminuindo conforme o aumento da idade. O consumo de tabaco e álcool é elevado nessa população, mas não influenciou as recidivas e as metástases da doença. Foi grande o tempo de evolução das lesões até a procura pelo serviço. CONCLUSÕES: Os baixos índices de sobrevida refletem a necessidade de uma maior atenção ao câncer bucal nessa população.BACKGROUND: The buccal cancer incidence in Brazil is one of the highest in the world. OBJECTIVES: To evaluate profile, risk factors and survival in patients with oral squamous cell carcinoma between 1982 and 2002 in a Brazilian population. MATERIAL AND METHOD: Age, gender, tumor site, previous clinical history

  7. Epidermal nevus syndrome.

    Laura, Flores-Sarnat


    Epidermal nevus syndrome (ENS) is an inclusive term for a heterogeneous group of congenital disorders characterized by the presence of epidermal nevi associated with systemic involvement. These disorders, as are all primary neurocutaneous syndromes, are neurocristopathies. The epidermal nevi that follow the lines of Blaschko and most systemic anomalies in skeletal, ocular, cardiovascular, endocrine, and orodental tissues, as well as lipomas, are due to defective neural crest. The most important and frequent anomaly in the brain in all forms of epidermal nevus syndromes (ENSs) is hemimegalencephaly (HME). This malformation often is not recognized, despite being the principal cause of neurological manifestations in ENSs. They consist mainly of epilepsy and developmental delay or intellectual disability. The onset of epilepsy in ENS usually is in early infancy, often as infantile spasms. Several syndromic forms have been delineated. I propose the term "Heide's syndrome" for those distinctive cases with the typical triad of hemifacial epidermal nevus, ipsilateral facial lipoma, and hemimegalencephaly. Most ENSs are sporadic. The mechanism is thought to be genetic mosaicism with a lethal autosomal dominant gene. Specific genetic mutations (PTEN, FGFR3, PIK3CA, and AKT1) have been documented in some patients. The large number of contributors for over more than a century and a half to the description of these disorders precludes the use of new author eponyms.

  8. Micromorphology and development of the epicuticular structure on the epidermal cell of ginseng leaves

    Kyounghwan Lee


    Conclusion: The outwardly projected cuticle and epidermal cell wall (i.e., an epicuticular wrinkle acts as a major barrier to block out sunlight in ginseng leaves. The small vesicles in the peripheral region of epidermal cells may suppress the cuticle and parts of epidermal wall, push it upward, and consequently contribute to the formation of the epicuticular structure.

  9. Penile Epidermal Inclusion Cyst

    M. El-Shazly


    Full Text Available We report a case of epidermal inclusion cyst in a 32-year-old male. This was a complication of circumcision that was neglected over years to form stones and urethrocutaneous fistula. Complete excision of the cyst and repair of the fistula were performed successfully. Histopathological examination confirmed our diagnosis.

  10. Epidermal Growth Factor and Intestinal Barrier Function

    Xiaopeng Tang


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


    Ana Maria Abreu Velez


    Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of

  12. Major vault protein supports glioblastoma survival and migration by upregulating the EGFR/PI3K signalling axis

    Lötsch, Daniela; Steiner, Elisabeth; Holzmann, Klaus; Spiegl-Kreinecker, Sabine; Pirker, Christine; Hlavaty, Juraj; Petznek, Helga; Hegedus, Balazs; Garay, Tamas; Mohr, Thomas; Sommergruber, Wolfgang; Grusch, Michael; Berger, Walter


    Despite their ubiquitous expression and high conservation during evolution, precise cellular functions of vault ribonucleoparticles, mainly built of multiple major vault protein (MVP) copies, are still enigmatic. With regard to cancer, vaults were shown to be upregulated during drug resistance development as well as malignant transformation and progression. Such in a previous study we demonstrated that human astrocytic brain tumours including glioblastoma are generally high in vault levels wh...

  13. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

    Deelen, Joris; Beekman, Marian; Uh, Hae-Won


    there was only moderate linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring...... the deleterious effects of the ApoE ε4 allele. No other major longevity locus was found....

  14. Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival.

    Miriam A Lynn

    Full Text Available BACKGROUND: Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28 has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28 and the retro-inverso form (RI-BMAP-28, as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages. METHODOLOGY/PRINCIPAL FINDINGS: An MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model. CONCLUSIONS/SIGNIFICANCE: Interestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant

  15. Clinical Studies on conformal radiotherapy combined with epidermal ...

    epidermal growth factor receptor-tyrosine kinase inhibitor in second-line treatment of non-small cell lung cancer. Yong Cai1, Ji-Ying Wang2 and .... Adenocarcinoma. 55. 118 ... survival, as risk factors, while EGFR mutation correlated with ...

  16. Posttraumatic stress disorder (PTSD in children after paediatric intensive care treatment compared to children who survived a major fire disaster

    Last Bob F


    Full Text Available Abstract Background The goals were to determine the presence of posttraumatic stress disorder (PTSD in children after paediatric intensive care treatment, to identify risk factors for PTSD, and to compare this data with data from a major fire disaster in the Netherlands. Methods Children completed the Dutch Children's Responses to Trauma Inventory at three and nine months after discharge from the paediatric intensive care unit (PICU. Comparison data were available from 355 children survivors who completed the same questionnaire 10 months after a major fire disaster. Results Thirty-six children aged eight to 17 years completed questionnaires at three month follow-up, nine month follow-up, or both. More than one third (34.5% of the children had subclinical PTSD, while 13.8% were likely to meet criteria for PTSD. Maternal PTSD was the strongest predictor for child PTSD. There were no significant differences in (subclinical PTSD symptoms either over time or compared to symptoms of survivors from the fire disaster. Conclusion This study shows that a considerable number of children have persistent PTSD after PICU treatment. Prevention of PTSD is important to minimize the profound adverse effects that PTSD can have on children's well-being and future development.

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

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


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

  18. Continuous epidermal growth factor receptor-tyrosine kinase inhibitor administration in primary lung adenocarcinoma patients harboring favorable mutations with controlled target lung tumors dose not hinder survival benefit despite small new lesions

    Ping-Chih Hsu


    Conclusion: Continuous EGFR-TKI administration in favorable EGFR-mutative lung adenocarcinoma patients with controlled primary tumors did not hinder the survival benefit, despite the appearance of new lesions.

  19. Niche interactions in epidermal stem cells

    Hye-Ryung Choi; Sang-Young Byun; Soon-Hyo Kwon; Kyoung-Chan Park


    Within the epidermis and dermis of the skin, cellssecrete and are surrounded by the extracellular matrix(ECM), which provides structural and biochemicalsupport. The ECM of the epidermis is the basementmembrane, and collagen and other dermal componentsconstitute the ECM of the dermis. There is significantvariation in the composition of the ECM of the epidermisand dermis, which can affect "cell to cell" and "cellto ECM" interactions. These interactions, in turn, caninfluence biological responses, aging, and woundhealing; abnormal ECM signaling likely contributes toskin diseases. Thus, strategies for manipulating cell-ECM interactions are critical for treating wounds and avariety of skin diseases. Many of these strategies focuson epidermal stem cells, which reside in a unique nichein which the ECM is the most important component;interactions between the ECM and epidermal stemcells play a major role in regulating stem cell fate. Asthey constitute a major portion of the ECM, it is likelythat integrins and type Ⅳ collagens are important instem cell regulation and maintenance. In this review,we highlight recent research-including our previouswork-exploring the role that the ECM and its associatedcomponents play in shaping the epidermal stem cellniche.

  20. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    Boer, Magdalena; Duchnik, Ewa; Maleszka, Romuald; Marchlewicz, Mariola


    The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transep...

  1. Targeting epidermal Langerhans cells by epidermal powder immunization


    Immune reactions to foreign or self-antigens lead to protective immunity and, sometimes, immune disorders such as allergies and autoimmune diseases. Antigen presenting cells (APC) including epidermal Langerhans cells (LCs) play an important role in the course and outcome of the immune reactions. Epidermal powder immunization (EPI) is a technology that offers a tool to manipulate the LCs and the potential to harness the immune reactions towards prevention and treatment of infectious diseases and immune disorders.

  2. Epidermal cell death in frogs with chytridiomycosis

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


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

  3. Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

    Vanessa Fiorini Furtado


    Full Text Available BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin 12 months (p-value = 0.030.CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

  4. Toxic epidermal necrolysis.

    Castelain, Florence; Humbert, Philippe


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

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

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


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

  6. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Oliveira-Cunha, Melissa, E-mail: [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Newman, William G. [Genetic Medicine, MAHSC, University of Manchester, St Mary' s Hospital, Oxford Road, Manchester, M13 9WL (United Kingdom); Siriwardena, Ajith K. [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom)


    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

  7. Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity Braquiterapia para carcinoma epidermóide do colo do útero estádio IIIB: sobrevida e toxicidade

    Antonio Carlos Zuliani


    Full Text Available OBJECTIVE: To compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR, high-dose-rate (HDR brachytherapy and association of HDR and chemotherapy. METHODS. Between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. RESULTS: The five-year progression-free survival (PFS was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02. The five-year Overall Survival (OS was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p = 0.02. Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. CONCLUSION: Patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups.OBJETIVO: Comparar três diferentes tratamentos para câncer de colo do útero, estádio IIIB: braquiterapia de baixa taxa de dose (LDR, alta taxa de dose (HDR e associação entre HDR e quimioterapia, quanto à sobrevida e toxicidade. MÉTODOS: Entre 1985 e 2005, 230 pacientes com carcinoma epidermoide de colo do útero estádio IIIB receberam teleterapia pélvica em quatro campos, doses entre 40 e 50.4 Gy, e três complementações diferentes. Grupo LDR, com 42 pacientes, recebeu uma ou duas inser

  8. Photoacoustic measurement of epidermal melanin

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


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

  9. Sparfloxacin induced toxic epidermal necrolysis

    Ramesh M


    Full Text Available Toxic epidermal necrolysis (TEN is a life-threatening cutaneous adverse drug reaction. TEN is known to occur with the fluoroquinolone class of antibiotics, but only four cases of sparfloxacin induced TEN have been reported to the WHO database. This is another case report of sparfloxacin induced TEN.

  10. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function.

    Boer, Magdalena; Duchnik, Ewa; Maleszka, Romuald; Marchlewicz, Mariola


    The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part - stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.

  11. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    Magdalena Boer


    Full Text Available The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.

  12. Epidermal nevus syndrome and dysplatic kidney disease.

    Azar Nickavar


    Full Text Available Epidermal nevus syndrome is a rare congenital disorder, characterized by epidermal nevi and multiple organ involvement. Multicystic kidney disease has been very rarely reported in this syndrome. Here is the report of a boy presented with multiple epidermal nevi, cardiac anomaly, seizure attack, hemi hypertrophy, and multicystic dysplastic kidney complicated with Wilms' tumor. According to this association, it is suggested to search for dysplastic kidney disease in patients with neurocutaneous disorders.

  13. Penile Epidermal Cyst: A Case Report

    Kumaraguru, Veerapandian; Prabhu, Ravi


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

  14. Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway.

    Koh, J. S.; Lieberthal, W; Heydrick, S; Levine, J. S.


    Lysophosphatidic acid (LPA) is the smallest and structurally simplest of all the glycerophospholipids. It occurs normally in serum and binds with high affinity to albumin, while retaining its biological activity. The effects of LPA are pleiotropic and range from mitogenesis to stress fiber formation. We show a novel role for LPA: as a macrophage survival factor with potency equivalent to serum. Administration of LPA protects macrophages from apoptosis induced by serum deprivation, and protect...

  15. Clinical characteristics and epidermal barrier function of papulopustular rosacea: A comparison study with acne vulgaris

    Zhou, Maosong; Xie, Hongfu; Cheng, Lin; Li, Ji


    Objective: To evaluate the clinical characteristics and epidermal barrier function of papulopustular rosacea by comparing with acne vulgaris. Methods: Four hundred and sixty-three papulopustular rosacea patients and four hundred and twelve acne vulgaris patients were selected for the study in Xiangya Hospital of Central South University from March 2015 to May 2016. They were analyzed for major facial lesions, self-conscious symptoms and epidermal barrier function. Results: Erythema, burning, ...

  16. Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats.

    Ardawi, M S


    1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Transcriptional profiling of epidermal differentiation.

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


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

  18. Effects of (-)-Epigallocatechin gallate on some protein factors involved in the epidermal growth factor receptor signaling pathway

    Yinjiu Huang; Ruiqing Xu; Baoan Song; Song Yang; Li Zhao; Shouwei Wua


    (-)-Epigallocatechin gallate (EGCG), a major polyphenolic constituent of green tea, can inhibit activity of specific receptor tyrosine kinases (RTKs) and related downstream signal transduction pathways, resulting in the control of unwanted cell proliferation. The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulates growth, survival, proliferation and differentiation in mammalian cells. This review addresses the effects of EGCG on some protein factors involved in the EGFR signaling pathway in a direct or indirect manner. Based on our understanding of the interaction between EGCG and these factors, and based on their structures, EGCG could be used as a lead compound for designing and synthesizing novel drugs with significant biological activity.

  19. Filaggrin and the great epidermal barrier grief.

    McGrath, John A


    One of the principal functions of human skin is to form an effective mechanical barrier against the external environment. This involves the maturation and death of epidermal keratinocytes as well as the assembly of a complex network of differentially and spatially expressed proteins, glycoproteins and lipids into the keratinocyte cell membrane and surrounding extracellular space. In 2006, the key role of the granular cell layer protein filaggrin (filament-aggregating protein) in maintaining the skin barrier was determined with the identification of loss-of-function mutations in the profilaggrin gene (FLG). These mutations have been shown to be the cause of ichthyosis vulgaris and a major risk factor for the development of atopic dermatitis, asthma associated with atopic dermatitis as well as systemic allergies. Mutations in the FLG gene are extremely common, occurring in approximately 9% of individuals from European populations. The remarkable discovery of these widespread mutations is expected to have a major impact on the classification and management of many patients with ichthyosis and atopic disease. It is also hoped that the genetic discovery of FLG mutations will lead to the future development of more specific, non-immunosuppressive treatments capable of restoring effective skin barrier function and alleviating or preventing disease in susceptible individuals.

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

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


    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. Psoriatic architecture constructed by epidermal remodeling.

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


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

  2. Epidermal electronic systems for sensing and therapy

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


    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.

  3. Simvastatin-induced Toxic Epidermal Necrolysis

    Emmanouil Petrou; Vasiliki Karali; Emmanouil Papadakis


    Toxic epidermal necrolysis comprises a severe immune-complex mediated hypersensitivity reaction that typically involves the skin and mucous membranes.Herein, we describe a68-year -old man who presented with the condition after simvastatin administration.

  4. Simvastatin-induced Toxic Epidermal Necrolysis

    Emmanouil Petrou


    Full Text Available Toxic epidermal necrolysis comprises a severe immune-complex mediated hypersensitivity reaction that typically involves the skin and mucous membranes. Herein, we describe a 68-year -old man who presented with the condition after simvastatin administration.

  5. Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin.

    Maubec, Eve; Laouénan, Cédric; Deschamps, Lydia; Nguyen, Van Tuan; Scheer-Senyarich, Isabelle; Wackenheim-Jacobs, Anne-Catherine; Steff, Maud; Duhamel, Stéphanie; Tubiana, Sarah; Brahimi, Nesrine; Leclerc-Mercier, Stéphanie; Crickx, Béatrice; Perret, Claudine; Aractingi, Selim; Escoubet, Brigitte; Duval, Xavier; Arnaud, Philippe; Jaisser, Frederic; Mentré, France; Farman, Nicolette


    A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in the epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by coadministration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate and eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents, or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect the epidermal thickness but coapplication of clobetasol and spironolactone significantly limited clobetasol-induced atrophy and was well tolerated. Altogether, these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy.

  6. Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

    Sforza, Vincenzo; Martinelli, Erika; Ciardiello, Fortunato; Gambardella, Valentina; Napolitano, Stefania; Martini, Giulia; della Corte, Carminia; Cardone, Claudia; Ferrara, Marianna L; Reginelli, Alfonso; Liguori, Giuseppina; Belli, Giulio; Troiani, Teresa


    The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them. PMID:27605871

  7. Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

    Jimenez-Zepeda, V H; Reece, D E; Trudel, S; Chen, C; Tiedemann, R; Kukreti, V


    The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

  8. Epidermal growth factor in the rat prostate

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier;


    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  9. Epidermal Inclusion Cysts of The Breast

    Amir R. Motabar


    Full Text Available Epidermal inclusion cysts are uncommon in the breast, but the consequences can besevere when these cysts occur in the breast parenchyma. Here,we report two suchcases. The patient in case 1 was an 37-year-old woman with a 3-cm palpable mass inthe right breast. Mammography revealed a round and smoothly outlined mass, whichindicated a benign tumor, and sonography showed an irregularly shaped and heterogeneoushypoechoic mass, fibroadenoma was suspected on the basis of clinical andimage findings, but excisional biopsy revealed an epidermal inclusion cyst. The patientin case 2 was a 50-year-old woman with a 2.5-cm lesion in the left breast. Mammographyrevealed a round, dense, smoothly outlined mass, and sonography showeda well-defined, central hyperechoic mass. . Breast cancer was suspected on the basisof the sonographic findings and the age of the patient, but the resected specimen revealedan epidermal inclusion cyst. Although epidermal inclusion cysts are benign,occasionally they may play a role in the origin of squamous carcinoma of the breast. .Mammographic and sonographic features of an epidermal cyst may mimic a malignantlesion. Malignant change appears to occur more frequently in epidermal inclusioncysts in the mammary gland, compared to common epidermal inclusion cysts,and this may be associated with origination of mammary epidermal inclusion cystsfrom squamous metaplasia of the mammary duct epithelium.Epidermmoid inclusion cyst of the breast is potentially serious, although such cystsare rare, and differentiation from a malignant or benign breast tumor is required. Excisionis probably the most appropriate treatment, and can eliminate the possible riskof malignant transformation.

  10. Rapidly Developing Toxic Epidermal Necrolysis

    Viktoria Oline Barrios Poulsen


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

  11. The role of GlcNAc-PI-de-N-acetylase gene by gene knockout through homologous recombination and its consequences on survival, growth and infectivity of Leishmania major in in vitro and in vivo conditions.

    Almani, Pooya Ghasemi Nejad; Sharifi, Iraj; Kazemi, Bahram; Babaei, Zahra; Bandehpour, Mojgan; Salari, Samira; Dezaki, Ebrahim Saedi; Tohidi, Farideh; Mohammadi, Mohammad Ali


    At present, there are no efficacious vaccines or effective drugs against leishmaniasis; therefore new and innovative control methods are urgently required. One way to achieve this important goal is through using reverse genetic engineering to evaluate important enzymes, proteins and macromolecules. One of the most important enzymes for Glycosylphosphatidylinositol (GPI) biosynthetic pathways is GlcNAc-PI-de-N-acetylase (GPI12). The molecular constructs were cloned in Escherichia coli strain Top 10 and confirmed by molecular methods and were transfected by electroporation into Leishmania major. We demonstrated that two alleles of the GPI12 gene in L. major were successfully removed and enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. We were able to produce a mutant parasite that caused no damaged to the host. Further investigations are essential to check the safety profile in laboratory animals.

  12. Mechanotransduction in epidermal Merkel cells.

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


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

  13. Strategies to overcome resistance to epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer.

    Jeong, Woo-Jeong; Cha, Pu-Hyeon; Choi, Kang-Yell


    Administration of monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR) such as cetuximab and panitumumab in combination with conventional chemotherapy substantially prolongs survival of patients with metastatic colorectal cancer (mCRC). However, the efficacy of these mAbs is limited due to genetic variation among patients, in particular K-ras mutations. The discovery of K-ras mutation as a predictor of non-responsiveness to EGFR mAb therapy has caused a major change in the treatment of mCRC. Drugs that inhibit transformation caused by oncogenic alterations of Ras and its downstream components such as BRAF, MEK and AKT seem to be promising cancer therapeutics as single agents or when given with EGFR inhibitors. Although multiple therapeutic strategies to overcome EGFR mAb-resistance are under investigation, our understanding of their mode of action is limited. Rational drug development based on stringent preclinical data, biomarker validation, and proper selection of patients is of paramount importance in the treatment of mCRC. In this review, we will discuss diverse approaches to overcome the problem of resistance to existing anti-EGFR therapies and potential future directions for cancer therapies related to the mutational status of genes associated with EGFR-Ras-ERK and PI3K signalings.

  14. Radiotracer Methods for Targeted Imaging of the Epidermal Growth Factor Receptor

    Jung, Kyung Ho; Lee, Kyung Han [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (Iressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

  15. Toxic epidermal necrolysis and Stevens-Johnson syndrome

    French Lars E


    using SCORTEN, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy. SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. More than 50% of patients surviving TEN suffer from long-term sequelae of the disease.

  16. Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer

    Berasain, Carmen, E-mail:; Latasa, María Ujue; Urtasun, Raquel; Goñi, Saioa; Elizalde, María; Garcia-Irigoyen, Oihane; Azcona, María [Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008 (Spain); Prieto, Jesús [Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008 (Spain); CIBERehd, University Clinic, University of Navarra, Pamplona 31080 (Spain); Ávila, Matías A. [Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008 (Spain)


    Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment.

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

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


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

  18. Carbamzepine-induced toxic epidermal necrolysis

    Nithyananda K Chowta


    Full Text Available Toxic epidermal necrolysis (TEN, also known as Lyell′s syndrome, is a widespread life-threatening mucocutaneous disease where there is extensive detachment of the skin and mucous membrane. Many factors involved in the etiology of TEN including adverse drug reactions. Here we are reporting a case of toxic epidermal necrolysis in an adult male patient after receiving carbamazepine in a 38 year old male. On the18th day of carbamazepine, patient developed blisters which first appeared on the trunk, chest and arms. The erythematous rash was covering almost all over the body with epidermal detachment of 70% body surface area. There was loss of eye lashes, congestion of conjunctiva with mucopurulent discharge and exposure keratitis. The clinical impression was TEN induced by carbamazepine. Carbamazepine was stopped immediately. He was treated with high dose intravenous betamethasone and systemic and topical antibiotics. After one month, the progression of the skin lesions halted and he was discharged.

  19. Epidermal melanin absorption in human skin

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


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

  20. SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation.

    Qiu, Weiming; Yang, Ke; Lei, Mingxing; Yan, Hongtao; Tang, Hui; Bai, Xiufeng; Yang, Guihong; Lian, Xiaohua; Wu, Jinjin


    Hair follicle melanocyte stem cells (McSCs) are responsible for hair pigmentation and also function as a major melanocyte reservoir for epidermal pigmentation. However, the molecular mechanism promoting McSCs for epidermal pigmentation remains elusive. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics key signaling involved in melanocyte growth, migration and differentiation. We therefore investigated the molecular basis for the contribution of hair follicle McSCs to epidermal pigmentation using the TPA induction model. We found that repetitive TPA treatment of female C57BL/6 mouse dorsal skin induced epidermal pigmentation by increasing the number of epidermal melanocytes. Particularly, TPA treatment induced McSCs to initiate proliferation, exit the stem cell niche and differentiate. We also demonstrated that TPA promotes melanoblast migration and differentiation in vitro. At the molecular level, TPA treatment induced robust expression of stem cell factor (SCF) in keratinocytes and c-kit in melanoblasts and melanocytes. Administration of ACK2, a neutralizing antibody against the Kit receptor, suppressed mouse epidermal pigmentation, decreased the number of epidermal melanocytes, and inhibited melanoblast migration. Taken together, our data demonstrate that TPA promotes the expansion, migration and differentiation of hair follicle McSCs for mouse epidermal pigmentation. SCF/c-kit signaling was required for TPA-induced migration and differentiation of hair follicle melanocytes. Our findings may provide an excellent model to investigate the signaling mechanisms regulating epidermal pigmentation from mouse hair follicle McSCs, and a potential therapeutic option for skin pigmentation disorders.

  1. Epidermal growth factor in mammary glands and milk from rats

    Thulesen, J; Raaberg, Lasse; Nexø, Ebba


    Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF-immunoreact......Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF......-immunoreactivity was revealed homogeneously in the cytoplasm of the secretory cells, which might suggest that EGF is present as a precursor molecule in the mammary glands. Altered glucose metabolism during lactation results in secondary hypoinsulinaemia in the lactating rat. As insulin is also known to affect lactation...... in several species, we treated normal lactating rats daily with insulin and studied the effect on the composition of milk. A significant increase in the content of total protein and milk fat was observed after a few days of insulin-treatment, as compared to a control group [total protein: 50 (36-97) g/l vs...

  2. Epidermal electrode technology for detecting ultrasonic perturbation of sensory brain activity.

    Huang, Stanley; Fisher, Jonathan A N; Ye, Meijun; Kim, Yun-Soung; Ma, Rui; Nabili, Marjan; Krauthamer, Victor; Myers, Matthew R; Coleman, Todd P; Welle, Cristin G


    We aim to demonstrate the in vivo capability of a wearable sensor technology to detect localized perturbations of sensory-evoked brain activity. Cortical somatosensory evoked potentials (SSEPs) were recorded in mice via wearable, flexible epidermal electrode arrays. We then utilized the sensors to explore the effects of transcranial focused ultrasound, which noninvasively induced neural perturbation. SSEPs recorded with flexible epidermal sensors were quantified and benchmarked against those recorded with invasive epidural electrodes. We found that cortical SSEPs recorded by flexible epidermal sensors were stimulus frequency-dependent. Immediately following controlled, focal ultrasound perturbation, the sensors detected significant SSEP modulation, which consisted of dynamic amplitude decreases and altered stimulus-frequency dependence. These modifications were also dependent on the ultrasound perturbation dosage. The effects were consistent with those recorded with invasive electrodes, albeit with roughly one order of magnitude lower signal-to-noise ratio. We found that flexible epidermal sensors reported multiple SSEP parameters that were sensitive to focused ultrasound. This work therefore (1) establishes that epidermal electrodes are appropriate for monitoring the integrity of major CNS functionalities through SSEP, and (2) leveraged this technology to explore ultrasound-induced neuromodulation. The sensor technology is well-suited for this application because the sensor electrical properties are uninfluenced by direct exposure to ultrasound irradiation. The sensors and experimental paradigm we present involve standard, safe clinical neurological assessment methods and are thus applicable to a wide range of future translational studies in humans with any manner of health condition.

  3. Phylogenetic and Systematic Value of Leaf Epidermal Characteristics in Some Members of Nigerian Fabaceae

    Gbenga Olorunshola Alege


    Full Text Available This study was undertaken at the Botanical Garden of Biological Sciences Department, Kogi State University, Anyigba with the aim of assessing the systematic and phylogenetic relevance of leaf epidermal attributes in the 10 selected species of Fabaceae. Stomata, trichomes and epidermal cell attributes were taken from adaxial and abaxial leaf surfaces. Results obtained in this study revealed that all the 10 plant species considered possess hypo-amphistomatic leaf condition, paracytic stomata type, polygon and irregular shape epidermal cells(on the abaxial surface which points to their common ancestry. All the analyzed leaf epidermal traits considered on the adaxial and abaxial surfaces showed significant variations among the 10 studied plant species which indicates that genetic diversity exists among members of Fabaceae for their delimitation. It was also observed that all the plants with tree habit considered in this study (i.e Delonix regia, Parkia biglobosa, Senna siamea, Daniella oliveri and Caesalpinia pulcherrima lack stomata on the adaxial surfaces which strongly suggest that absence of stomata on the adaxial surface may be peculiar to Legumes with such habit. Cluster analysis revealed 2 major clusters and 2 sub-clusters with the first cluster comprising only Senna siamea and Caesalpinia pulcherrima which confirms their close phylogenetic relationship. Variations in trichomes, stomata and epidermal attributes were obvious and could be used to resolve systematic and phylogenetic problems in this family.

  4. Epidermal inclusion cyst as a rare complication of neonatal male circumcision: a case report

    Okeke Linus Ikechukwu


    Full Text Available Abstract Introduction Ibadan, Nigeria, has a very high rate of complications of male circumcision. In a previous survey, redundant or excessive loss of foreskin, skin bridges and injury to the glans penis were the major types of complications identified. Epidermal inclusion cyst complicating neonatal male circumcision appears to be extremely rare, and an extensive search of all databases revealed no reports in the recent literature. Case presentation In 1992, a 10-year-old boy was seen at the urology outpatients clinic presenting with a globular swelling in the penile skin located at the ventral surface proximal to the coronal sulcus. The histology of the excised mass revealed an epidermal inclusion cyst. Since then, he has remained healthy. Conclusions Epidermal inclusion cyst complicating male neonatal circumcision is extremely rare. The diagnosis is easy and a simple total excision is curative.

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

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


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

  6. Stevens Johnsons syndrom og toksisk epidermal nekrolyse

    Kaur-Knudsen, Diljit; Zachariae, Claus; Thomsen, Simon Francis


    Stevens-Johnson syndrome and toxic epidermal necrolysis are acute mucocutaneous diseases primarily due to drug intake. The diseases are characterised by the separation of epidermis from dermis which can be life-threatening. Mortality is often caused by sepsis and multiple organ failure. The most...

  7. Carbamate pesticide induced toxic epidermal necrolysis

    Rajendran N


    Full Text Available A 36-year-old male alleged to have consumed carbamate pesticide liquid (Baygon@ developed toxic epidermal necrolysis (TEN within twenty-four hours of intake. Though drugs have been commonly incriminated as offending agents for TEN, carbamate pesticide was found to be the causative agent in our case.

  8. Perforator Flaps after Excision of Large Epidermal Cysts in the Buttocks

    Sang Wha Kim


    Full Text Available 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.

  9. Hybrid Enhanced Epidermal SpaceSuit Design Approaches

    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.

  10. Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients.

    Mazzarella, Luca; Disalvatore, Davide; Bagnardi, Vincenzo; Rotmensz, Nicole; Galbiati, Donata; Caputo, Sara; Curigliano, Giuseppe; Pelicci, Pier Giuseppe


    Obesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours. We assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER-) HER2+ cases. In ER-/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI>30) versus normal/underweight (BMIobese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups. Obesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER-/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Evaluation of dermal substitute in a novel co-transplantation model with autologous epidermal sheet.

    Guofeng Huang

    Full Text Available The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with dermal substitutes to repair full-thickness skin defects. Autologous epidermal sheets were obtained by digesting the basement membrane (BM and dermal components from rat split-thickness skins in Dispase II solution (1.2 u/ml at 4 °C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining showed that the epidermal sheet preserved an intact epidermis without any BM or dermal components, and a high percentage of viable cells (92.10 ± 4.19% and P63 positive cells (67.43 ± 4.21% under an optimized condition. Porcine acellular dermal matrixes were co-transplanted with the autologous epidermal sheets to repair full-thickness skin defects in Sprague-Dawley rats. The epidermal sheets survived and completely re-covered the wounds within 3 weeks. Histological staining showed that the newly formed stratified epidermis attached directly onto the dermal matrix. Inflammatory cell infiltration and vascularization of the dermal matrix were not significantly different from those in the subcutaneous implantation model. Collagen IV and laminin distributed continuously at the epidermis and dermal matrix junction 4 weeks after transplantation. Transmission electron microscopy further confirmed the presence of continuous lamina densa and hemidesmosome structures. This novel animal model can be used not only to observe the biocompatibility of dermal substitutes, but also to evaluate their effects on new epidermis and BM formation. Therefore, it is a simple and reliable model for evaluating the safety and efficacy of dermal substitutes.

  12. Abnormal epidermal changes after argon laser treatment

    Neumann, R.A.; Knobler, R.M.; Aberer, E.; Klein, W.; Kocsis, F.; Ott, E. (Univ. of Vienna (Austria))


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

  13. Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis.

    Blunder, Stefan; Rühl, Ralph; Moosbrugger-Martinz, Verena; Krimmel, Christine; Geisler, Anita; Zhu, Huiting; Crumrine, Debra; Elias, Peter M; Gruber, Robert; Schmuth, Matthias; Dubrac, Sandrine


    Loss-of-function mutations in the FLG gene cause ichthyosis vulgaris (IV) and represent the major predisposing genetic risk factor for atopic dermatitis (AD). Although both conditions are characterized by epidermal barrier impairment, AD also exhibits signs of inflammation. This work was aimed at delineating the role of FLG loss-of-function mutations on eicosanoid metabolism in IV and AD. Using human epidermal equivalents (HEEs) generated with keratinocytes isolated from nonlesional skin of patients with FLG wild-type AD (WT/WT), FLG-mutated AD (FLG/WT), IV (FLG/FLG), or FLG WT control skin, we assessed the potential autocrine role of epidermal-derived eicosanoids in FLG-associated versus FLG-WT AD pathogenesis. Ultrastructural analyses demonstrated abnormal stratum corneum lipid architecture in AD and IV HEEs, independent of FLG genotype. Both AD (FLG/WT) and IV (FLG/FLG) HEEs showed impaired late epidermal differentiation. Only AD (FLG/WT) HEEs exhibited significantly increased levels of inflammatory cytokines. Analyses of lipid mediators revealed increased arachidonic acid and 12-lipoxygenase metabolites. Whereas treatment of control HEEs with arachidonic acid increased expression of inflammatory cytokines, 12-hydroxy-eicosatetraenoic acid attenuated expression of late differentiation markers. Thus, FLG mutations lead to alterations in epidermal eicosanoid metabolism that could serve as an autocrine trigger of inflammation and impaired late epidermal differentiation in AD.

  14. Changes of epidermal thickness in vitiligo.

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


    The stratum corneum and epidermal pigmentation have protective roles against ultraviolet radiation. Because vitiligo skin lacks melanocytes and has no potential to produce pigment, some studies suggested that the epidermis in vitiligo skin is thicker than in normal skin. However, only a few studies investigated epidermal thickness changes in vitiligo, and some of these had relatively small sample sizes. Thus, this study aimed to compare epidermal thickness between vitiligo skin and adjacent normal-appearing skin in a large cohort. Photos of hematoxylin and eosin–stained slides of vitiligo skin and adjacent normal-appearing skin were taken under a microscope. The thicknesses of the stratum corneum, viable epidermis, and full epidermis were then measured by a computerized image analyzer. A total of 206 patients (412 sections) were included. There were significant differences between vitiligo skin and adjacent normal-appearing skin in the thickness of the stratum corneum (P = 0.009), viable epidermis (P = 0.001), and total epidermis (P = 0.001). An analysis comparing skin biopsied from a sun-exposed area versus a sun-protected area showed that the stratum corneum, viable epidermis, and total epidermis were significantly thicker in vitiligo skin than in normal-appearing skin in sun-exposed areas (P vitiligo skin than in normal-appearing skin, especially on sun-exposed skin, and that this may represent a photoprotective role compensating for absent pigmentation.

  15. The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation

    Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar;


    The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...... wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells. In contrast, the epidermal expression of complement components was downregulated in ex vivo injured skin lacking the stimulation from infiltrating inflammatory cells but with intact injury......-induced epidermal growth factor receptor (EGFR)-mediated growth factor response. In cultured primary keratinocytes, stimulation with the potent EGFR ligand, TGF-α, yielded a significant downregulation of complement component expression. Indeed, EGFR inhibition significantly enhanced the induction of complement...

  16. Modelling survival

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight


    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...... the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how...

  17. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells.

    Poulin, Lionel Franz; Henri, Sandrine; de Bovis, Béatrice; Devilard, Elisabeth; Kissenpfennig, Adrien; Malissen, Bernard


    Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express the lectin langerin and that reside in their immature state in epidermis. Paradoxically, in mice permitting diphtheria toxin (DT)-mediated ablation of LCs, epidermal LCs reappeared with kinetics that lagged behind that of their putative progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed that a major fraction of the langerin(+), skin-derived DCs found in LNs originates from a developmental pathway that is independent from that of epidermal LCs. This pathway, the existence of which was unexpected, originates in the dermis and gives rise to langerin(+) dermal DCs (DDCs) that should not be confused with epidermal LCs en route to LNs. It explains that after DT treatment, some langerin(+), skin-derived DCs reappear in LNs long before LC-derived DCs. Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin(+) DDCs were found to coexist in wild-type mice. Moreover, DT-mediated ablation of epidermal LCs opened otherwise filled niches and permitted repopulation of adult noninflammatory epidermis with BM-derived LCs. Our results stress that the langerin(+) DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models.

  18. c-Jun promotes whereas JunB inhibits epidermal neoplasia.

    Jin, Jane Y; Ke, Hengning; Hall, Russell P; Zhang, Jennifer Y


    Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant-negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor-suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to

  19. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    Chang, Shih-Chieh [Department of Internal Medicine, National Yang-Ming University Hospital, Yilan 260, Taiwan (China); Chang, Cheng-Yu [Department of Chest Medicine, Far Eastern Memorial Hospital, Taipei 220, Taiwan (China); Shih, Jin-Yuan, E-mail: [Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)


    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects.

  20. Computational Modeling of Cell Survival Using VHDL

    Shruti Jain1,


    Full Text Available The model for cell survival has been implemented using VeryHigh Speed Integrated Circuit Hardware DescriptionLanguage (VHDL (Xilinx Tool taking three input signals:Tumor necrosis factor-α (TNF, Epidermal growth factor(EGF and Insulin. Cell survival has been regulated by theinteraction of five proteins viz P13K, TNFR1, EGFR, IRS andIKK in a network. In the absence of any one, in protein networkleads to cell death. For the EGF input signal the proteins likeMEK, ERK, AkT, Rac & JNK have been important forregulation of cell survival. Similarly for TNF and Insulin inputsignal proteins like NFκB, AkT, XIAP, JNK, MAP3K & MK2and MEK, ERK, AkT, Rac, mTOR & JNK respectively havebeen important for regulation of cell survival.

  1. The role of epidermal growth factor receptor in photodynamic therapy: a review of the literature and proposal for future investigation.

    Martínez-Carpio, Pedro A; Trelles, Mario A


    The epidermal growth factor receptor (EGFR) pathway seems to be an important contributor to the antiproliferative response to photodynamic therapy (PDT), in terms of cell death, apoptosis and tumour destruction. We reviewed all preclinical investigations in the scientific literature on the role of the EGFR pathway in PDT. A systematic search of Medline-indexed references up to March 2010 using the recommended strategies for Medline information retrieval and identifying relevant studies from systematic reviews, revealed 16 full articles that were exhaustively analysed. EGFR inhibition/degradation appeared to be a major effect of PDT in all investigations. PDT was found to result in a time-dependent reduction of EGFR expression, inhibition of tyrosine phosphorylation and induction of apoptosis during the regression of tumours. Within the time period of the PDT reaction, normal and malignant cells lose their responsiveness to EGF. The ERK1/2 and EGFR-PI3K-Akt pathways seem to be involved in cellular survival after PDT. Pharmacotherapy and immunotherapy to block EGFR activity combined with PDT seem to be very effective in reducing malignant tumours in vivo. The effect of PDT is associated with inactivation of the EGFR pathway, but biochemical and cellular phenomena are important and scarcely investigated. EGFR inhibitors and PDT act synergistically, and this is highly relevant for clinical use.

  2. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma.

    Charlotta Hedner

    Full Text Available Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR and 3 (HER3, as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma.Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology.High EGFR expression was an independent risk factor for shorter overall survival (OS, whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods.

  3. Local Epidermal Growth Factor Receptor Signaling Mediates the Systemic Pathogenic Effects of Staphylococcus aureus Toxic Shock Syndrome.

    Laura M Breshears

    Full Text Available Secreted factors of Staphylococcus aureus can activate host signaling from the epidermal growth factor receptor (EGFR. The superantigen toxic shock syndrome toxin-1 (TSST-1 contributes to mucosal cytokine production through a disintegrin and metalloproteinase (ADAM-mediated shedding of EGFR ligands and subsequent EGFR activation. The secreted hemolysin, α-toxin, can also induce EGFR signaling and directly interacts with ADAM10, a sheddase of EGFR ligands. The current work explores the role of EGFR signaling in menstrual toxic shock syndrome (mTSS, a disease mediated by TSST-1. The data presented show that TSST-1 and α-toxin induce ADAM- and EGFR-dependent cytokine production from human vaginal epithelial cells. TSST-1 and α-toxin also induce cytokine production from an ex vivo porcine vaginal mucosa (PVM model. EGFR signaling is responsible for the majority of IL-8 production from PVM in response to secreted toxins and live S. aureus. Finally, data are presented demonstrating that inhibition of EGFR signaling with the EGFR-specific tyrosine kinase inhibitor AG1478 significantly increases survival in a rabbit model of mTSS. These data indicate that EGFR signaling is critical for progression of an S. aureus exotoxin-mediated disease and may represent an attractive host target for therapeutics.

  4. Ultrastructural and biochemical analysis of epidermal xanthophores and dermal chromatophores of the teleost Sparus aurata

    Ferrer, C.; Solano, F.; Zuasti, A


    We have studied the pigmentary system of the teleost Sparus aurata skin by electron microscopy and chromatographic analysis. Under electron microscopy, we found the dermis to contain the three major types of recognized chromatophores: melanophores, xanthophores and iridophores. Melanophores were more abundant in the dorsal region, whereas the iridophores were more abundant in the ventral region. The most important discovery was that of epidermal xanthophore...

  5. Pseudosindactilia en epidermólisis bullosa


    La epidermólisis bullosa comprende un grupo de patologías que se caracterizan por la fragilidad de la piel, formación de ampollas, y en las formas distróficas, la formación de pseudosindactilias. Debido a lo exótico de la entidad y la dificultad para el enfoque de tratamiento, se presenta un caso clínico con desarrollo de pseudosindactilias, característico usualmente de las formas distróficas. Se describe en aspectos clínicos de la entidad, el tratamiento quirúrgico de las pseudosindactilias...

  6. Giant epidermal cyst of the tarsal plate

    Mohana Majumdar


    Full Text Available A 35-year-old male patient presented with a right upper eyelid mass with mechanical ptosis. The patient gave no history of trauma or surgery. On examination, there was a huge cystic mass fixed to the tarsal plate. Excisional biopsy with tarsectomy was done. Histopathology sections demonstrated a keratin-filled cyst arising from the tarsus. A thorough Pubmed search did not reveal an epidermal cyst of the tarsal plate of this size which was successfully managed. The incision was made in such a way that postoperative ptosis would be avoided. Excess skin was removed during the surgery.

  7. Epidermal cell density is autoregulated via a secretory peptide, EPIDERMAL PATTERNING FACTOR 2 in Arabidopsis leaves.

    Hara, Kenta; Yokoo, Toshiya; Kajita, Ryoko; Onishi, Takaaki; Yahata, Saiko; Peterson, Kylee M; Torii, Keiko U; Kakimoto, Tatsuo


    Regulation of the number of cells is critical for development of multicellular organisms. During plant epidermal development, a protodermal cell first makes a fate decision of whether or not to be the meristemoid mother cell (MMC), which undergoes asymmetric cell division forming a meristemoid and its sister cell. The MMC-derived lineage produces all stomatal guard cells and a large proportion of non-guard cells. We demonstrate that a small secretory peptide, EPIDERMAL PATTERING FACTOR 2 (EPF2), is produced by the MMC and its early descendants, and negatively regulates the density of guard and non-guard epidermal cells. Our results suggest that EPF2 inhibits cells from adopting the MMC fate in a non-cell-autonomous manner, thus limiting the number of MMCs. This feedback loop is critical for regulation of epidermal cell density. The amino acid sequence of EPF2 resembles that of EPF1, which is known to control stomatal positioning. Over-expression of EPF1 also inhibits stomatal development, but EPF1 can act only on a later developmental process than EPF2. Overexpression and promoter swapping experiments suggested that the protein functions of EPF1 and EPF2, rather than the expression patterns of the genes, are responsible for the specific functions. Although targets of EPF1 and EPF2 are different, both EPF1 and EPF2 require common putative receptor components TOO MANY MOUTHS (TMM), ERECTA (ER), ERECTA LIKE 1 (ERL1) and ERL2 in order to function.

  8. Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis.

    Augustin, Iris; Gross, Julia; Baumann, Daniel; Korn, Claudia; Kerr, Grainne; Grigoryan, Tamara; Mauch, Cornelia; Birchmeier, Walter; Boutros, Michael


    Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδ(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.

  9. Genetic variation in the epidermal transglutaminase genes is not associated with atopic dermatitis.

    Agne Liedén

    Full Text Available BACKGROUND: Atopic dermatitis (AD is a common chronic inflammatory skin disorder where epidermal barrier dysfunction is a major factor in the pathogenesis. The identification of AD susceptibility genes related to barrier dysfunction is therefore of importance. The epidermal transglutaminases (TGM1, TGM3 and TGM5 encodes essential cross-linking enzymes in the epidermis. OBJECTIVE: To determine whether genetic variability in the epidermal transglutaminases contributes to AD susceptibility. METHODS: Forty-seven single nucleotide polymorphisms (SNPs in the TGM1, TGM3 and TGM5 gene region were tested for genetic association with AD, independently and in relation to FLG genotype, using a pedigree disequilibrium test (PDT in a Swedish material consisting of 1753 individuals from 539 families. In addition, a German case-control material, consisting of 533 AD cases and 1996 controls, was used for in silico analysis of the epidermal TGM regions. Gene expression of the TGM1, TGM3 and TGM5 gene was investigated by relative quantification with Real Time PCR (qRT-PCR. Immunohistochemical (IHC analysis was performed to detect TG1, TG3 and TG5 protein expression in the skin of patients and healthy controls. RESULTS: PDT analysis identified a significant association between the TGM1 SNP rs941505 and AD with allergen-specific IgE in the Swedish AD family material. However, the association was not replicated in the German case-control material. No significant association was detected for analyzed SNPs in relation to FLG genotype. TG1, TG3 and TG5 protein expression was detected in AD skin and a significantly increased TGM3 mRNA expression was observed in lesional skin by qRT-PCR. CONCLUSION: Although TGM1 and TGM3 may be differentially expressed in AD skin, the results from the genetic analysis suggest that genetic variation in the epidermal transglutaminases is not an important factor in AD susceptibility.

  10. Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

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


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

  11. [Epidermal growth factor receptor expression and epidermal growth factor blood plasma content in simple and complex endometrial hyperplasia].

    Dznelashvili, N; Kasradze, D; Tavartkiladze, A; Mariamidze, A


    The goal of our study was to concurrently determine the prognostic significance of Epidermal Growth Factor Receptor (EGFR) expression in endometrium and Epidermal Growth Factor (EGF) blood content in simple and complex hyperplasia. In order to detect EGFR expression, immunohistochemical examination of endometrial scarp from 35 patients was done along with HPLC (High performance liquid chromatography) method, for measuring EGF blood plasma content. The numerical data obtained were processed statistically using computer program SPSS-12. According to the results: 1. A significant/marked increase in EGF blood plasma level together with pronounced EGFR expression in simple endometrial hyperplasia (without atypia) suggests that simple hyperplasia is likely to transform into complex form, while unchanged level of EGF against the background of mild EGFR expression is probably indicative of not very bad prognosis. 2. Normal indices of EGF blood plasma level in simple endometrial hyperplasia (without atypia), accompanied by mild EGFR expression is suggestive of good prognosis. 3. A sharp or extremely sharp increase in EGF blood plasma level with pronounced EGFR expression in complex endometrial hyperplasia (without atypia) is likely to indicate poor prognosis that may lead to the transformation into atypical form. However, unchanged EGF blood plasma level against the background of mild EGFR expression in complex endometrial hyperplasia (without atypia) is likely to point to not very bad prognosis. 4. A marked increase in EGF blood plasma level with a pronounced EGFR expression in complex endometrial hyperplasia (without atypia) is likely to indicate poor prognosis that may lead to the transformation into atypical form. Because it is evident that drastic increase in EGF blood plasma level is not necessary, other factor should be suspected to play the major role, i.e the substance that will (or will not) withstand neoplasia.

  12. Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2' patients

    Dréanic, Johann; Dhooge, Marion; Barret, Maximilien; Brezault, Catherine; Mir, Olivier; Chaussade, Stanislas; Coriat, Romain


    Background In metastatic colorectal cancer, the modified Glasgow prognostic score (mGPS) has been approved as an independent prognostic indicator of survival. No data existed on poor prognosis patients treated with molecular-targeted agents. Methods From January 2007 to February 2012, patients with metastatic colorectal cancer and poor predictive survival score (mGPS = 2), treated with 5-fluorouracil-based chemotherapy in addition to an anti-epidermal growth factor receptor (EGFR) or anti-vas...

  13. Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review

    Amartej Merla


    Full Text Available Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF, has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.

  14. Toxic epidermal necrolysis, DRESS, AGEP : Do overlap cases exist?

    Bouvresse, Sophie; Valeyrie-Allanore, Laurence; Ortonne, Nicolas; Konstantinou, Marie Pauline; Kardaun, Sylvia H.; Bagot, Martine; Wolkenstein, Pierre; Roujeau, Jean-Claude


    Background: Severe cutaneous adverse reactions to drugs (SCARs) include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and epidermal necrolysis (Stevens-Johnson syndrome-toxic epidermal necrolysis [SJS-TEN]). Because of the varied ini

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

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


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

  16. Survival Analysis

    Miller, Rupert G


    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

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

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


    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.

  18. Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

    Poulsen, Steen Seier


    The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300...... mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also...... factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition...

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

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


    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.

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

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


    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

  1. Herbal medicines that benefit epidermal permeability barrier function

    Lizhi Hu


    Full Text Available Epidermal permeability barrier function plays a critical role in regulating cutaneous functions. Hence, researchers have been searching for effective and affordable regimens to enhance epidermal permeability barrier function. In addition to topical stratum corneum lipids, peroxisome proliferator-activated receptor, and liver X receptor ligands, herbal medicines have been proven to benefit epidermal permeability barrier function in both normal and diseased skin, including atopic dermatitis, glucocorticoid-induced skin damage, and UVB-damaged skin. The potential mechanisms by which herbal medicines improve the permeability barrier include stimulation of epidermal differentiation, lipid production, antimicrobial peptide expression, and antioxidation. Therefore, utilization of herbal medicines could be a valuable alternative approach to enhance epidermal permeability barrier function in order to prevent and/or treat skin disorders associated with permeability barrier abnormalities.

  2. Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling.

    Lim, Xinhong; Tan, Si Hui; Koh, Winston Lian Chye; Chau, Rosanna Man Wah; Yan, Kelley S; Kuo, Calvin J; van Amerongen, Renée; Klein, Allon Moshe; Nusse, Roel


    The skin is a classical example of a tissue maintained by stem cells. However, the identity of the stem cells that maintain the interfollicular epidermis and the source of the signals that control their activity remain unclear. Using mouse lineage tracing and quantitative clonal analyses, we showed that the Wnt target gene Axin2 marks interfollicular epidermal stem cells. These Axin2-expressing cells constitute the majority of the basal epidermal layer, compete neutrally, and require Wnt/β-catenin signaling to proliferate. The same cells contribute robustly to wound healing, with no requirement for a quiescent stem cell subpopulation. By means of double-labeling RNA in situ hybridization in mice, we showed that the Axin2-expressing cells themselves produce Wnt signals as well as long-range secreted Wnt inhibitors, suggesting an autocrine mechanism of stem cell self-renewal.

  3. Ultrastructural and biochemical analysis of epidermal xanthophores and dermal chromatophores of the teleost Sparus aurata.

    Ferrer, C; Solano, F; Zuasti, A


    We have studied the pigmentary system of the teleost Sparus aurata skin by electron microscopy and chromatographic analysis. Under electron microscopy, we found the dermis to contain the three major types of recognized chromatophores: melanophores, xanthophores and iridophores. Melanophores were more abundant in the dorsal region, whereas the iridophores were more abundant in the ventral region. The most important discovery was that of epidermal xanthophores. Epidermal xanthophores were the only chromatophores in the epidermis, something only found in S aurata and in a teleost species living in the Antartic sea. In contrast, the biochemical analysis did not establish any special characteristics: we found pteridine and flavin pigments located mostly in the pigmented dorsal region. Riboflavin and pterin were two of the most abundant coloured pigment types, but other colourless pigments such as xanthopterin and isoxanthopterin were also detected.

  4. Epidermóide intra-raqueano

    Antonio B. Lefèvre


    Full Text Available Caso de tumor epidermóides intra-raqueano, extra-medular ao nível de T12, diagnosticado e tratado cirùrgicamente, em um menino de 9 anos. Os autores chamam a atenção para a dificuldade diagnostica deste caso, cujo quadro clínico lembrava o de uma radiculopatia compressiva por hérnia de disco intervertebral. A evolução foi favorável, com recuperação total, sem seqüelas. Lembram os autores a necessidade de ser precizada a designação dêsses tumores, que são muitas vêzes confundidos com os cistos dermóides e outros tumores congênitos.

  5. Toxic Epidermal Necrolysis Caused by Amoxicillin

    Celalettin Sever


    Full Text Available Toxic epidermal necrolysis (TEN is a severe skin reaction related to drugs and infections, characterized by fever, stomatitis and conjunctivitis. Many drug related TEN cases have been reported in literature but amoxicillin related TEN cases are rare. In this article, a case of amoxicillin related severe TEN in a female patient during treatment of tonsillitis has been reported. The increased use of amoxicillin, especially for control of infection, may be the reason for the increased incidence TEN due to the same drug. The identification of a drug as the cause for the immune related cytotoxic reaction may be difficult if the molecule is not generally known to be a classical cause of this reaction.

  6. Epidermal growth factor in the rat lung

    Raaberg, Lasse; Poulsen, Steen Seier; Nexø, Ebba


    Epidermal Growth Factor (EGF) in pharmacological doses is able to induce precoccious lung maturation in rabbits and sheeps. As EGF is probably acting in a para- or autocrine way, we have searched for EGF in the lungs. We report EGF immunoreactivity to be present in the type II pneumocytes...... of the rat from a couple of days prior to birth and throughout life. Further, we report EGF immunoreactivity to be present in cells in the bronchi and the bronchioles from day 20-21 of gestation and throughout life. G-200 gelchromatography of lung extracts indicates that the EGF-reactive material is a high...... molecular weight form of EGF. Since previous studies have shown that EGF in pharmacological doses is able to promote lung maturation, our results may imply a physiological role for EGF in the lungs....

  7. Tyrosine Kinase Domain Gene Polymorphism of Epidermal Growth Factor Receptor in Gastric Cancer in Northern Iran

    Jeivad F


    Full Text Available Background: Gastric cancer is one of the most common diseases of digestive system with a low 5-year survival rate and metastasis is the main cause of death. Multi-factors, such as changes in molecular pathways and deregulation of cells are involved in the disease development. Epidermal growth factor receptor pathway (EGFR which is associated with cell proliferation and survival can influence cancer development. EGFR function is governed by its genetic polymorphism; thus, we aimed to study the tyrosine kinase domain gene mutations of the receptor in patients with gastric cancer.Methods : In this experimental study, 123 subjects (83 patients with gastric cancer and 40 normal subjects were investigated in north of Iran for EGFR gene polymorphisms during 1 year. Genomic DNA was extracted by DNA extraction kit according to the manufacture's protocol. Polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP and silver staining were performed for investigating EGFR gene polymorphisms. Results : The participants included 72 men and 44 women. Gene polymorphism in exon 18 was present in 10% of the study population but SSCP pattern in exon 19 did not show different migrate bands neither in patients nor in normal subjects.Conclusion: It seems that screening for tyrosine kinas gene polymorphism of epidermal growth factor receptor in patients with gastric cancer and use of tyrosine kinas inhibitors could be useful in the prevention of disease progress and improvement of treatment process for a better quality of life in these patients.

  8. Staphylococcus hyicus virulence in relation to exudative epidermitis in pigs

    Wegener, Henrik Caspar; Andresen, Lars Ole; Bille-Hansen, Vivi


    Staphylococcus hyicus strains with different phage types, plasmid profiles, and antibiotic resistance patterns were isolated from piglets with exudative epidermitis. The strains could be divided into virulent strains, producing exudative epidermitis, and avirulent strains, producing no dermal....... It is concluded that crusting reaction of piglet skin is a suitable indicator of virulence in S. hyicus in relation to exudative epidermitis, and that virulent strains produce a 30 kDa protein, absent in concentrated culture supernatants from avirulent strains. This 30 kDa protein might be an exfoliative toxin....

  9. Surviving Objects

    Murjas, Teresa


    Surviving Objects (2012) is a devised multi-media practice-as-research performance based on extensive interviews conducted with my elderly mother and recorded on a hand-held device. Our conversations concern her experiences as a child refugee following violent deportation by the Soviet Army from Eastern Poland to Siberia (1941), and her subsequent route, via Persia, to a British-run refugee camp in Northern Rhodesia, where she remained for 6 years before arriving in the UK. In order to aid my...

  10. [New routes of administration: epidermal, transcutaneous mucosal ways of vaccination].

    Denis, François; Alain, Sophie; Ploy, Marie-Cécile


    A successful vaccine triggers the interaction of various cells of the immune system as does a regular immune response. It is thus necessary to introduce the vaccine antigens into an anatomic site where they will contact immune cells. The route of administration is thus critical for the outcome of vaccination. Intramuscular or subcutaneous injections are the most popular. Antigens injected intramuscularly can form persistent precipitates that are dissolved and re-absorbed relatively slowly. If injecting antigens is a quick, easy and reproducible way to vaccination, it requires trained personnel. Alternatives exist, through non-invasive formulations which allow administration by the patient or a third party with no particular expertise. The skin, especially its epidermal layer, is an accessible and competent immune environment and an attractive target for vaccine delivery, through transcutaneous delivery or immunostimulant patches. Mucosal immunization is another strategy: its major rationale is that organisms invade the body via mucosal surfaces. Therefore, local protection at mucosal surface as well as systemic defense is beneficial. Various formulations of mucosal vaccines have been developed, such as the Sabin oral polio vaccine (OPV), rotavirus vaccines, cold-adapted influenza vaccines or vaccine against typhoid fever. Thus we are entering in an era where mucosal and transcutaneous immunisation will play an important role in disease management. However, it has not been so easy to obtain regulatory approval for mucosal or transcutaneous formulations and needle-based vaccines continue to dominate the market.

  11. Langerhans Cells Facilitate UVB-induced Epidermal Carcinogenesis

    Lewis, Julia M.; Bürgler, Christina D.; Freudzon, Marianna; Golubets, Kseniya; Gibson, Juliet F.; Filler, Renata B.; Girardi, Michael


    Ultraviolet B (UVB) light is considered the major environmental inducer of human keratinocyte DNA mutations, including within the tumor-suppressor gene p53, and chronic exposure is associated with cutaneous squamous cell carcinoma (SCC) formation. Langerhans cells (LC) comprise a dendritic network within the suprabasilar epidermis, yet the role of LC in UVB-induced carcinogenesis is largely unknown. Herein, we show that LC-intact epidermis develops UVB-induced tumors more readily than LC-deficient epidermis. While levels of epidermal cyclopyrimidine dimers (CPD) following acute UVB exposure are equivalent in the presence or absence of LC, chronic UVB-induced p53 mutant clonal islands expand more readily in association with LC which remain largely intact and are preferentially found in proximity to the expanding mutant keratinocyte populations. The observed LC facilitation of mutant p53 clonal expansion is completely αβ and γδ T-cell independent, and is associated with increased intraepidermal expression of interleukin (IL)-22 and the presence of group 3 innate lymphoid cells (ILC3). These data demonstrate that LC play a key role in UVB-induced cutaneous carcinogenesis, and suggest that LC locally stimulate keratinocyte proliferation and innate immune cells that provoke tumor outgrowth. PMID:26053049

  12. Nutrition in Toxic Epidermal Necrolysis: A Multicenter Review.

    Graves, Caran; Faraklas, Iris; Maniatis, Katelynn; Panter, Elizabeth; La Force, Jessica; Aleem, Razia; Zavala, Sarah; Albrecht, Marlene; Edwards, Paul; Cochran, Amalia


    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe exfoliative diseases treated in burn centers due to large skin losses. Literature on SJS/TEN refers to parenteral nutrition (PN) as the preferred route of nutrition support. This study describes nutrition support interventions in SJS/TEN patients admitted to burn centers. Seven burn centers participated in this Institutional Review Board-exempted retrospective chart review of adults with SJS/TEN admitted from 2000-2012. This analysis included 171 patients with SJS/TEN. Median total body surface area involvement was 35% (n = 145; interquartile range [IQR], 16%-62%). The majority required mechanical ventilation (n = 105). Based on indirect calorimetry, measured energy needs were 24.2 kcal/kg of admit weight (n = 58; IQR, 19.4-29.9). Thirty-one patients did not require enteral nutrition (EN) and started oral intake on hospital day 1 (IQR, 1-2), and 81% required EN support due to inadequate oral intake and remained on EN until day 16 (median hospital day, 16; IQR, 9-25). High-protein enteral formulas predominated. PN was rarely used (n = 12, 7%). Most patients were discharged home (57%), with 14% still requiring EN. Nutrition support should be considered in patients with SJS/TEN due to increased metabolic needs and an inability to meet these needs orally. Most SJS/TEN patients continued on EN and did not require escalation to PN. © 2016 American Society for Parenteral and Enteral Nutrition.

  13. Sodium-calcium exchanger and multiple sodium channel isoforms in intra-epidermal nerve terminals

    Gasser Andreas


    Full Text Available Abstract Background Nociception requires transduction and impulse electrogenesis in nerve fibers which innervate the body surface, including the skin. However, the molecular substrates for transduction and action potential initiation in nociceptors are incompletely understood. In this study, we examined the expression and distribution of Na+/Ca2+ exchanger (NCX and voltage-gated sodium channel isoforms in intra-epidermal free nerve terminals. Results Small diameter DRG neurons exhibited robust NCX2, but not NCX1 or NCX3 immunolabeling, and virtually all PGP 9.5-positive intra-epidermal free nerve terminals displayed NCX2 immunoreactivity. Sodium channel NaV1.1 was not detectable in free nerve endings. In contrast, the majority of nerve terminals displayed detectable levels of expression of NaV1.6, NaV1.7, NaV1.8 and NaV1.9. Sodium channel immunoreactivity in the free nerve endings extended from the dermal boundary to the terminal tip. A similar pattern of NCX and sodium channel immunolabeling was observed in DRG neurons in vitro. Conclusions NCX2, as well as NaV1.6, NaV1.7, NaV1.8 and NaV1.9, are present in most intra-epidermal free nerve endings. The presence of NCX2, together with multiple sodium channel isoforms, in free nerve endings may have important functional implications.


    Abdullahi Alanamu ABDULRAHAMAN


    Full Text Available Herbal medicine is the oldest and still the most widely used system of medicine in the world today and they are made exclusively from plants. However, most of these medicines or drugs are adulterated due to lack of proper identification of the plant samples. Method of checking adulteration of drug plants is the main focus of this study. The identification and authentication of dry samples of some medicinal plants were carried out using anatomical features. Twenty-five (25 plants materials were collected in Ibadan and Ilorin, Nigeria. The plants studied include Azardiracta indica, Newboudia leavis, Polyalthia longifolia, Cymbopogon citratus, Anarcardium occidentalis, Nicotiana tobbaccum, Jatropha curcas, Chromoleana odorata, Mangifera indica, Terminalia catappa, Ocimum gratisimum, Morus messosygia, Morinda lucida, Psidium guajava, Vitellaria paradoxa, Annona senegalensis, Vernonia amygdalina, Gliricidium sepium, Ravoulvia vomitora, Telferia occindentalis Citrus aurantifolia, C. limon, C. paradisi and C. sinensis. Leaf epidermal anatomy of these selected plants showed no major variations in stomatal complex types, frequency, size and shape of stomatal cells, epidermal cell wall and trichomes between fresh and dry samples. The variations that occur were between different species but not within species. Leaf epidermal anatomy, therefore, proved to be a significant tool for resolution of taxonomic confusion of dried samples of these plants.

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

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


    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.

  16. Fatal toxic epidermal necrolysis associated with minoxidil.

    Karaoui, Lamis R; Chahine-Chakhtoura, Corinne


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

  17. Clinical and Microscopic Characteristics of Canine Toxic Epidermal Necrolysis

    Banovic, F; Olivry, T; Bazzle, L; Tobias, J. R; Atlee, B; Zabel, S; Hensel, N; Linder, K. E


    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...

  18. Epidermal Nevus Syndrome Associated with Brain Malformations and Medulloblastoma

    J Gordon Millichap


    Full Text Available Researchers at Juntendo University and Tokyo Women’s Medical University, Japan; and University of California, San Francisco, Ca, report a male infant with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

  19. Pattern of hormone receptors and human epidermal growth factor ...


    Feb 5, 2015 ... Key words: Breast cancer, human epidermal growth factor receptor 2/neu, immunohistochemistry, ... therapy.[6‑8] Of all these prognostic and predictive factors, ... one of the biggest private medical laboratories in Nigeria.

  20. the significance of epidermal growth factor receptor and survivin ...


    Jan 1, 2013 ... SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE ... Objective: To assess whether epidermal growth factor receptor (EGFR) and survivin ..... lung cancer by the FDA in 2003 (28) and is currently.

  1. Epidermal and dermal integumentary structures of ankylosaurian dinosaurs.

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


    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.

  2. Evaluation of Epidermal Skin Grafts for the Treatment of Complex Wounds in a Wound Care Center: A 94-Patient Case Series.

    Lincoln, Katherine; Hyde, Jessica


    In recent years, a new technology for autologous epidermal harvesting has been developed to produce epidermal skin grafts (ESGs) for use over wounds. This technology employs negative pressure and heat to raise the epidermal skin layer, allowing for consistent and reproducible epidermal harvesting. The aim of this case series is to present the authors' experience using an automated, epidermal harvesting system to produce ESGs to treat wounds of patients with multiple comorbidities. This case series was conducted between January 1, 2013 and December 31, 2014. Patients with wounds (≤ 25 cm2) that failed to heal were treated with ESGs by a group of 3 wound care physicians in 2 outpatient wound care centers in a community health center setting. A total of 94 patients with 102 wounds were identified. Of the 94 patients, 3 were noncompliant and 9 were lost to follow-up. Therefore, 82 patients with 90 wounds were included in the analysis. The majority of wounds demonstrated epithelialization (83/90, 92.2%). Of the 90 wounds, 75 (83.3%) healed following epidermal grafting, 4 (4.4%) wounds displayed improvement, and 11 (12.2%) did not heal. Minimal or no pain at the donor site was reported by the patients, and all donor sites healed without complications. This case series provides additional evidence for the use of ESGs for the treatment of wounds that fail to heal.

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

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


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

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

    Esquirol Caussa, Jordi; Herrero Vila, Elisabeth


    Bioidentical recombinant human epidermal growth factor (rhEGF) is available in concentrations and purity suitable for therapeutic use in long time stable formulations. Beneficial effects in several skin pathologies and lesions have been reported (traumatic and surgical wound healing, laser induced wounds, abnormal scars, keloids, radiation or chemotherapy induced dermatitis, post inflammatory hyperpigmentation or for skin aging damage repairing) and also may be considered for the treatment of several oropharingeal and high gastroesophageal tract mucosa diseases (mouth sores, pharyngeal fistulas, ulcers), and several corneal or conjunctive mucosa lesions. rhEGF has not shown any important side or collateral effects in humans or in laboratory experimentation animals, showing optimal tolerability and safety with continuous use for months. Compounding gives advantages of versatility, individualization, personalization, molecular stability, safety and effectiveness in ideal conditions, showing good tissue penetration, both on intact skin and skin lesions that expose the lower planes to the surface. rhEGF compounds can be considered for prevention or as a treatment of diverse skin and mucosa diseases and conditions through compounding preparations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. Epidermal growth factor (urogastrone) in human tissues.

    Hirata, Y; Orth, D N


    Human epidermal growth factor (hEGF), which stimulates the growth of a variety of tissues, was first isolated from mouse submandibular glands, but is also excreted in large amounts (about 50 micrograms/day) in human urine and is probably identical to human beta-urogastrone (hUG), a potent inhibitor of stimulated gastric acid secretion. However, the primary tissue source of hEGF/hUG is as yet unknown. The hEGF/hUG in homogenates of human salivary glands and a wide variety of other endocrine and nonendocrine tissues was extracted by Amberlite CG-50 cation exchange chromatography and immune affinity chromatography using the immunoglobulin fraction of rabbit anti-hEGF serum covalently bound to agarose. The extracts were subjected to homologous hEGF RIA. Immunoreactive hEGF was found in extracts of adult submandibular gland, thyroid gland, duodenum, jejunum, and kidney, but not in several fetal tissues. The tissue immunoreactive hEGF was similar to standard hEGF in terms of immunoreactivity and elution from Sephadex G-50 Fine resin, but its concentrations were very low (1.3-5.5 ng/g wet tissue). Thus, it is not certain that these tissues represent the only source of the large amounts of hEGF/hUG that appear to be filtered by the kidneys each day.

  6. Epidermal transglutaminase (TGase 3 is required for proper hair development, but not the formation of the epidermal barrier.

    Susan John

    Full Text Available Transglutaminases (TGase, a family of cross-linking enzymes present in most cell types, are important in events as diverse as cell-signaling and matrix stabilization. Transglutaminase 1 is crucial in developing the epidermal barrier, however the skin also contains other family members, in particular TGase 3. This isoform is highly expressed in the cornified layer, where it is believed to stabilize the epidermis and its reduction is implicated in psoriasis. To understand the importance of TGase 3 in vivo we have generated and analyzed mice lacking this protein. Surprisingly, these animals display no obvious defect in skin development, no overt changes in barrier function or ability to heal wounds. In contrast, hair lacking TGase 3 is thinner, has major alterations in the cuticle cells and hair protein cross-linking is markedly decreased. Apparently, while TGase 3 is of unique functional importance in hair, in the epidermis loss of TGase 3 can be compensated for by other family members.

  7. Specification of Epidermal Cell Fate in Plant Shoots

    Shinobu eTakada


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

  8. Tight junction regulates epidermal calcium ion gradient and differentiation

    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya [Pola Chemical Industries Inc., 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812 (Japan); Sasaki, Hiroyuki, E-mail: [Division of Fine Morphology, Core Research Facilities, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461 (Japan); The Center for Advanced Medical Engineering and Infomatics, Osaka University, Osaka 565-0871 (Japan)


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

  9. A potential peptide therapeutic derived from the juxtamembrane domain of the epidermal growth factor receptor.

    Aislyn D W Boran

    Full Text Available The epidermal growth factor receptor (EGFR is involved in many cancers and EGFR has been heavily pursued as a drug target. Drugs targeting EGFR have shown promising clinical results for several cancer types. However, resistance to EGFR inhibitors often occurs, such as with KRAS mutant cancers, therefore new methods of targeting EGFR are needed. The juxtamembrane (JXM domain of EGFR is critical for receptor activation and targeting this region could potentially be a new method of inhibiting EGFR. We hypothesized that the structural role of the JXM region could be mimicked by peptides encoding a JXM amino acid sequence, which could interfere with EGFR signaling and consequently could have anti-cancer activity. A peptide encoding EGFR 645-662 conjugated to the Tat sequence (TE-64562 displayed anti-cancer activity in multiple human cancer cell types with diminished activity in non-EGFR expressing cells and non-cancerous cells. In nude mice, TE-64562 delayed MDA-MB-231 tumor growth and prolonged survival, without inducing toxicity. TE-64562 induced non-apoptotic cell death after several hours and caspase-3-mediated apoptotic cell death with longer treatment. Mechanistically, TE-64562 bound to EGFR, inhibited its dimerization and caused its down-regulation. TE-64562 reduced phosphorylated and total EGFR levels but did not inhibit kinase activity and instead prolonged it. Our analysis of patient data from The Cancer Genome Atlas supported the hypothesis that down-regulation of EGFR is a potential therapeutic strategy, since phospho- and total-EGFR levels were strongly correlated in a large majority of patient tumor samples, indicating that lower EGFR levels are associated with lower phospho-EGFR levels and presumably less proliferative signals in breast cancer. Akt and Erk were inhibited by TE-64562 and this inhibition was observed in vivo in tumor tissue upon treatment with TE-64562. These results are the first to indicate that the JXM domain of EGFR

  10. Epidermal growth factor induces changes of interaction between epidermal growth factor receptor and actin in intact cells

    Wei Song; Haixing Xuan; Qishui Lin


    The epidermal growth factor receptor (EGFR) is a cyto-skeleton-binding protein. Although purified EGFR can interact with actins in vitro and normally at least 10% of EGFR exist in the insoluble cytoskeleton fraction of A431 cells, interaction of cytosolic EGFR with actin can only be visualized by fluorescence resonance energy transfer when epidermal growth factor presents in the cell medium. Results indicate that the correct orientation between EGFR and actin is important in the signal transduction process.

  11. Major Roads

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for major roads (interstates and trunk highways) found on the USGS 1:24,000 mapping series. These roadways are current...

  12. Major Links.

    Henderson, Tona


    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  13. Surviving cyberwar

    Stiennon, Richard


    This book examines in depth the major recent cyber attacks that have taken place around the world, discusses the implications of such attacks, and offers solutions to the vulnerabilities that made these attacks possible. Through investigations of the most significant and damaging cyber attacks, the author introduces the reader to cyberwar, outlines an effective defense against cyber threats, and explains how to prepare for future attacks.

  14. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    Bor, M V; Sørensen, B S; Vinter-Jensen, L


    as the expression of transforming growth factor-alpha peptide. The level of epidermal growth factor receptor and transforming growth factor-alpha mRNA expression was found to correlate both in control and growth factor-treated animals, whereas the expression of epidermal growth factor receptor and epidermal growth...

  15. Fluorescence lifetime to image epidermal ionic concentrations

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


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

  16. Metabolic epidermal necrosis-hepatocutaneous syndrome.

    Byrne, K P


    It is clear that cutaneous lesions of metabolic epidermal necrosis in the dog can occur either with a demonstrable glucagon-secreting tumor or with hepatic disease without any detectable glucagonoma. Additional clinical case reports of the disease in cats are needed to better characterize the disease in this species. The lesions of NME-MEN may not represent a specific physiological mechanism of cutaneous disease but instead a pathophysiological process that can be triggered by several systemic metabolic abnormalities. The fact that NME is observed in association with a variety of conditions supports the theory that an overall metabolic derangement results in the rash. The prognosis for canine MEN is poor; however, some affected dogs have been maintained for many months with dietary management. High-quality protein diets such as Hill's Prescription Diet a/d (Hill's Pet Products) or other "recovery" diets may be helpful. Zinc and essential fatty acid supplementation may help some patients. Dietary supplementation with cooked egg yolks may be helpful. It is prudent to avoid corticosteroids in these cases, as development of diabetes mellitus worsens the prognosis. Histopathological examination of the pancreas coupled with determination of plasma glucagon may help define the characteristics of GS versus HS in dogs. It is possible that some dogs diagnosed with MEN-HS may have an undetected pancreatic tumor. Although the hepatic ultrasound findings in dogs with MEN-HS are becoming well characterized, it is possible for dogs with pancreatic neuroendocrine tumors to also have abnormal hepatic ultrasonography. As the presence of MEN and hepatic disease does not necessarily rule out the presence of a pancreatic tumor, prospective studies correlating plasma glucagon levels with pancreatic histopathology in cases of MEN-GS versus MEN-HS seem warranted.

  17. c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia

    Jin, Jane Yingai; Ke, Hengning; Hall, Russell P.; Zhang, Jennifer Y.


    Deregulation of the AP1 family gene regulators have been implicated in a wide range of diseases, including cancer. Here, we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven b...

  18. Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis.

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


    Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.

  19. Long-Term Stability and Safety of Transgenic Cultured Epidermal Stem Cells in Gene Therapy of Junctional Epidermolysis Bullosa

    Laura De Rosa


    Full Text Available We report a long-term follow-up (6.5 years of a phase I/II clinical trial envisaging the use of autologous genetically modified cultured epidermal stem cells for gene therapy of junctional epidermolysis bullosa, a devastating genetic skin disease. The critical goals of the trial were to evaluate the safety and long-term persistence of genetically modified epidermis. A normal epidermal-dermal junction was restored and the regenerated transgenic epidermis was found to be fully functional and virtually indistinguishable from a normal control. The epidermis was sustained by a discrete number of long-lasting, self-renewing transgenic epidermal stem cells that maintained the memory of the donor site, whereas the vast majority of transduced transit-amplifying progenitors were lost within the first few months after grafting. These data pave the way for the safe use of epidermal stem cells in combined cell and gene therapy for genetic skin diseases.

  20. Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy

    Bryan A Faller


    Full Text Available Bryan A Faller, Barbara BurtnessDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USAAbstract: Pancreatic adenocarcinoma is a common malignancy that remains refractory to available therapies. Gemcitabine has long been the standard, first-line agent in advanced disease. The epidermal growth factor receptor (EGFR is a commonly expressed target in pancreatic cancer that is involved in tumor proliferation, metastasis, and induction of angiogenesis. The addition of the EGFR inhibitor erlotinib to gemcitabine has recently been demonstrated to provide a small, yet statistically significant, survival benefit in advanced disease. This has prompted further research into the applications of EGFR-targeted therapy in pancreatic cancer, albeit with disappointing results. Resistance to these therapies seems highly prevalent and has been implicated in their limited efficacy. The development of rash is associated with treatment efficacy and suggests that predictive factors may one day be identified to guide appropriate patient selection for these agents. Preclinical research has shown promise that resistance to EGFR-targeted therapies can be overcome through a variety of approaches. Application of this research in clinical trials may ultimately yield an unquestioned role for EGFR-targeted therapy in the management of this disease.Keywords: cetuximab, drug resistance, epidermal growth factor receptor, erlotinib, gemcitabine, pancreatic cancer

  1. ATML1 promotes epidermal cell differentiation in Arabidopsis shoots.

    Takada, Shinobu; Takada, Nozomi; Yoshida, Ayaka


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

  2. Ultraviolet absorption and epidermal-transmittance spectra in foliage

    Day, T.A.; Howells, B.W.; Rice, W.J. (Dept. of Biology, West Virginia Univ., Morgantown, WV (United States))


    We examined the UV absorption spectra and the epidermal-transmittance spectra (280-350 nm) of foliage from 42 plant species. Sun foliage was sampled from naturally growing individuals of seven species in each of six life forms comprising two evergreen groups (gymnosperms and angiosperms) and four deciduous angiosperm groups (trees, shrubs and vines, herbaceous dicotyledons and grasses). There were large differences in absorption spectra of whole-leaf extracts among species. While absorbance declined with increasing wavelength in most woody species, there was a through in absorbance around 300 nm in many herbaceous species. Absorption spectra were negatively correlated with epidermal-transmittance spectra in 31 of the 42 species. Relationships between absorbance and transmittance did not follow the theoretical exponential function. Species rankings of UV-screening effectiveness were similar when we assessed it by using epidermal transmittance at single wavelengths (300 or 320 nm) or different UV-action spectra to weight epidermal-transmittance spectra and estimate the levels of biologically effective UV reaching the mesophyll. Thus, differences in absolute epidermal transmittance among species appeared to overshadow spectral differences. Nevertheless, the differences we found in the internal UV spectral regime in foliage suggest that whole-plant action spectra will differ among species. While species rankings of UV-screening effectiveness were similar when different action spectra were used, the absolute amounts of biologically effective UV reaching the mesophyll of species varied considerably when different action spectra were used. (au) (46 refs.)

  3. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    Dailey, G.E.; Kraus, J.W.; Orth, D.N.


    Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +- 3.0 and 52.0 +- 3.5 (mean +- SE) vol, or 29.7 +- 1.1 and 39.8 +- 1.7 creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 creatinine; P < 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and ..beta..-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +- 2.6 creatinine) than normal men, but this was not significant (P > 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.

  4. Topography of human placental receptors for epidermal growth factor.

    Rao, C V; Ramani, N; Chegini, N; Stadig, B K; Carman, F R; Woost, P G; Schultz, G S; Cook, C L


    These studies were undertaken to determine whether term human placental microvillus plasma membranes, which are exposed to maternal blood, and basolateral plasma membranes, which are in close proximity to fetal blood capillaries, contain receptors for epidermal growth factor (EGF). These two highly purified membranes bound 125I-EGF with similar affinity (apparent dissociation constants, 0.07-0.12 nM, but the total number of available receptors was greater in microvillus (8.2 pmol/mg protein) compared to basolateral (4.9 pmol/mg protein) plasma membranes. Detailed characterization of 125I-EGF binding to these membranes revealed numerous similarities as well as differences. The two membranes contained two major (155 and 140 kDa) and at least three minor (115, 175, and 210 kDa) specific 125I-EGF binding proteins. The 115-kDa protein was only found in basolateral plasma membranes. The 155-kDa protein was predominantly labeled in microvillus, whereas the 140-kDa protein was labeled predominantly in basolateral plasma membranes. The addition of protease inhibitors did not alter the multiple 125I-EGF binding proteins pattern found in these membranes. EGF stimulated phosphorylation of 140- and 155-kDa proteins in both microvillus and basolateral plasma membranes. However, the 155-kDa protein was phosphorylated to a greater extent in microvillus, whereas both 140- and 155-kDa proteins were phosphorylated equally in basolateral plasma membranes. Light and electron microscope autoradiographic studies revealed that 125I-EGF preferentially associated with microvillus plasma membranes. The data demonstrates the presence of EGF receptors in outer cell membranes of syncytiotrophoblasts and suggests that maternal EGF may influence syncytiotrophoblast function by binding to receptors in microvillus plasma membranes, while fetal EGF may also influence syncytiotrophoblast function but via receptors in basolateral plasma membranes.

  5. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    Shih-Chieh Chang


    Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI, was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects.

  6. Epidermal growth factor receptor inhibitors in colorectal cancer treatment: What's new?


    Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefitinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response.

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

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


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

  8. Getting under the skin of epidermal morphogenesis.

    Fuchs, Elaine; Raghavan, Srikala


    At the surface of the skin, the epidermis serves as the armour for the body. Scientists are now closer than ever to understanding how the epidermis accomplishes this extraordinary feat, and is able to survive and replenish itself under the harshest conditions that face any tissue. By combining genetic engineering with cell-biological studies and with human genome data analyses, skin biologists are discovering the mechanisms that underlie the development and differentiation of the epidermis and hair follicles of the skin. This explosion of knowledge paves the way for new discoveries into the genetic bases of human skin disorders and for developing new therapeutics.

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

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


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

  10. KRAS mutational status as a predictor of epidermal growth factor receptor inhibitor efficacy in colorectal cancer.

    Baynes, Roy D; Gansert, Jennifer


    Inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated promising potential in the treatment of advanced colorectal cancer. However, a proportion of patients do not respond to therapy with EGFR inhibitors, and therefore, there has been interest in identifying those patients most likely to benefit from therapy with these agents. KRAS, a member of the RAS family of signaling proteins, plays an important role in EGFR-mediated regulation of cellular proliferation and survival. Although there is still some debate regarding the prognostic importance of KRAS mutations in patients with metastatic colorectal cancer, several recent phase 2 and 3 studies have identified the presence of mutations at codons 12 and 13 of KRAS as predictors of poor response to the anti-EGFR monoclonal antibodies panitumumab and cetuximab. Patients with wild-type KRAS were found to have significantly better progression-free survival, overall survival, and/or objective response rate compared with patients harboring KRAS mutations. As a result, there has been growing interest in the development of KRAS mutational status as a biomarker for predicting patient response to EGFR-targeted therapy. Screening colorectal tumors for the absence of KRAS mutations may help identify patients most likely to benefit from anti-EGFR therapies.

  11. Deficiency in milk fat globule-epidermal growth factor-factor 8 exacerbates organ injury and mortality in neonatal sepsis.

    Hansen, Laura W; Khader, Adam; Yang, Weng-Lang; Jacob, Asha; Chen, Tracy; Nicastro, Jeffrey M; Coppa, Gene F; Prince, Jose M; Wang, Ping


    Neonatal sepsis is a systemic inflammation occurring in neonates because of a proven infection within the first 28days of birth. It is the third leading cause of morbidity and mortality in the newborns. The mechanism(s) underlying the systemic inflammation in neonatal sepsis has not been completely understood. We hypothesize that the deficiency of milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a protein commonly found in human milk, could be responsible for the increased inflammatory response leading to morbidity and mortality in neonatal sepsis. Male and female newborn mice aged 5-7days were injected intraperitoneally with 0.9mg/g body weight cecal slurry (CS). At 10h after CS injection, they were euthanized, and blood, lungs and gut tissues were obtained for further analyses. Control newborn mice underwent similar procedures with the exception of the CS injection. In duplicate newborn mice after CS injection, they were returned to their respective cages with their mothers and were closely monitored for 7days and survival rate recorded. At 10h after CS injection, serum LDH in the MFG-E8 knockout (KO) newborn mice was significantly increased by 58% and serum IL-6, IL-1β and TNF-α in the MFG-E8KO newborn mice were also significantly increased by 56%, 65%, and 105%, respectively, from wild type (WT) newborn mice. There were no significant difference between WT control and MFG-E8 control newborn mice. The lung architecture was severely damaged and a significant 162% increase in injury score was observed in the CS MFG-E8KO newborn mice. The MPO, TUNEL staining, and cytokine levels in the lungs and the intestine in CS MFG-E8KO newborn mice were significantly increased from CS WT newborn mice. Similarly, intestinal integrity was also compromised in the CS MFG-E8KO newborn mice. In a survival study, while the mortality rate within 7days was only 29% in the CS WT newborn mice, 80% of the CS MFG-E8KO newborn mice died during the same time period with the

  12. Prognostic impact of epidermal growth factor receptor (EGFR expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer

    Ychou Marc


    Full Text Available Abstract Background Epidermal growth factor receptor (EGFR represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT. Methods Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. Results Median age was 64 years (range: 30–88. Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+ was observed in 43 patients (56%. Median follow-up was 36 months (range: 6–86. Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98% and 84% (CI 95%, 58–95%, respectively (P = 0.06. Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037, rectal resection with microscopic residue (hazard ratio = 6.92, CI 95

  13. Epidermal Inclusion Cyst Presenting as a Palpable Scrotal Mass

    Andres F. Correa


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

  14. Toxic epidermal necrolysis and agranulocytosis: Rare adverse effects of ciprofloxacin

    Upadya Gatha


    Full Text Available Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis. One case of granulocytopenia, four of pancytopenia and fifteen of leucopenia worldwide have been reported. With the use of ciprofloxacin becoming more and more widespread, these two rare but fatal complications of ciprofloxacin should be borne in mind.

  15. Radiotherapy and receptor of epidermal growth factor; Radiotherapie et recepteur de l'Epidermal Growth Factor

    Deberne, M. [Institut Gustave-Roussy, 94 - Villejuif (France)


    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  16. Epidermal Growth Factor Receptor Mutation Is Associated With Longer Local Control After Definitive Chemoradiotherapy in Patients With Stage III Nonsquamous Non–Small-Cell Lung Cancer

    Yagishita, Shigehiro [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Horinouchi, Hidehito, E-mail: [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Katsui Taniyama, Tomoko; Nakamichi, Shinji; Kitazono, Satoru; Mizugaki, Hidenori; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Shiraishi, Kouya; Kohno, Takashi [Division of Genome Biology, National Cancer Center Research Institute, Tokyo (Japan); Furuta, Koh [Department of Clinical Laboratories, National Cancer Center Hospital, Tokyo (Japan); Tsuta, Koji [Department of Pathology, National Cancer Center Hospital, Tokyo (Japan); Tamura, Tomohide [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan)


    Purpose: To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non–small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT). Patients and Methods: Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated. Results: A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR. Conclusions: Our study is the first to show radiosensitive biology of EGFR-mutated tumors in definitive CRT with curative intent. This finding could serve as a credible baseline estimate of EGFR-mutated population in stage III nonsquamous NSCLC.

  17. Squamous cell carcinoma arising from an epidermal cyst in the thumb

    Akio Sakamoto


    Discussion and conclusion: The clinical symptoms of squamous cell carcinoma arising from an epidermal cyst can mimic those of an infected epidermal cyst. The current report facilitates awareness of such disease.

  18. EGFR-ras-raf signaling in epidermal stem cells: roles in hair follicle development, regeneration, tissue remodeling and epidermal cancers.

    Doma, Eszter; Rupp, Christian; Baccarini, Manuela


    The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research mainly focuses on its role in cutaneous tumor initiation and maintenance, much less is known about Ras signaling in the epidermal stem cells, which are the main targets of skin carcinogenesis. In this review, we briefly discuss the properties of the epidermal stem cells and review the role of EGFR-Ras-Raf signaling in keratinocyte stem cells during homeostatic and pathological conditions.

  19. Gamma-linolenic acid in borage oil reverses epidermal hyperproliferation in guinea pigs.

    Chung, S; Kong, S; Seong, K; Cho, Y


    As dietary sources of gamma-linolenic acid [GLA; 18:3(n-6)], borage oil (BO; 24-25 g/100 g GLA) and evening primrose oil (PO; 8-10 g/100 g GLA) are efficacious in treating skin disorders. The triglycerol stereospecificity of these oils is distinct, with GLA being concentrated in the sn-2 position of BO and in the sn-3 position of PO. To determine whether the absolute level and/or the triglycerol stereospecificity of GLA in oils affect biological efficacy, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 wk. Subsequently, guinea pigs were fed diets of PO, BO or a mixture of BO and safflower oil (SO) for 2 wk. The mixture of BO and SO (BS) diet had a similar level of GLA as PO but with sn-2 stereospecificity. As controls, two groups were fed SO and HCO for 10 wk. Epidermal hyperproliferation was reversed by all three oils in the order of BO > BS > PO. However, proliferation scores of group PO were higher than of the normal control group, SO. The accumulations of dihomo-gamma-linolenic acid [DGLA; 20:3(n-6)], an elongase product of GLA, into phospholipids and ceramides, of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent antiproliferative metabolite of DGLA, and of ceramides, the major lipid maintaining epidermal barrier, in the epidermis of group BO were greater than of groups BS and PO. Group BS had higher levels of DGLA, 15-HETrE and ceramides than group PO. With primary dependence on absolute levels, our data demonstrate that the antiproliferative efficacy of GLA in the epidermis is preferably exerted from sn-2 stereospecificity of GLA in BO.

  20. Comparative Genomics Identifies Epidermal Proteins Associated with the Evolution of the Turtle Shell.

    Holthaus, Karin Brigit; Strasser, Bettina; Sipos, Wolfgang; Schmidt, Heiko A; Mlitz, Veronika; Sukseree, Supawadee; Weissenbacher, Anton; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold


    The evolution of reptiles, birds, and mammals was associated with the origin of unique integumentary structures. Studies on lizards, chicken, and humans have suggested that the evolution of major structural proteins of the outermost, cornified layers of the epidermis was driven by the diversification of a gene cluster called Epidermal Differentiation Complex (EDC). Turtles have evolved unique defense mechanisms that depend on mechanically resilient modifications of the epidermis. To investigate whether the evolution of the integument in these reptiles was associated with specific adaptations of the sequences and expression patterns of EDC-related genes, we utilized newly available genome sequences to determine the epidermal differentiation gene complement of turtles. The EDC of the western painted turtle (Chrysemys picta bellii) comprises more than 100 genes, including at least 48 genes that encode proteins referred to as beta-keratins or corneous beta-proteins. Several EDC proteins have evolved cysteine/proline contents beyond 50% of total amino acid residues. Comparative genomics suggests that distinct subfamilies of EDC genes have been expanded and partly translocated to loci outside of the EDC in turtles. Gene expression analysis in the European pond turtle (Emys orbicularis) showed that EDC genes are differentially expressed in the skin of the various body sites and that a subset of beta-keratin genes within the EDC as well as those located outside of the EDC are expressed predominantly in the shell. Our findings give strong support to the hypothesis that the evolutionary innovation of the turtle shell involved specific molecular adaptations of epidermal differentiation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Inhibition of the epidermal growth factor receptor in bladder cancer cells treated with the DNA-damaging drug etoposide markedly increases apoptosis

    Munk, Mathias; Memon, Ashfaque Ahmed; Nexo, Ebba


    OBJECTIVE: To investigate the effect of the epidermal growth factor receptor (EGFR) on the induction of apoptosis by the chemotherapeutic agent etoposide (VP16), and to examine the effect of combining VP16 with gefitinib to see if the cell-survival mechanism can be prevented. MATERIALS AND METHOD...... suggest that activation of the EGFR induced a cell-survival function when bladder cancer cells were treated with the DNA-damaging drug VP16, and that combined treatment with VP16 and the EGFR inhibitor gefitinib might improve the efficacy of treatment. Udgivelsesdato: 2007-Jan...

  2. Stevens-Johnson syndrome and toxic epidermal necrolysis: an update on pharmacogenetics studies in drug-induced severe skin reaction.

    Rufini, Sara; Ciccacci, Cinzia; Politi, Cristina; Giardina, Emiliano; Novelli, Giuseppe; Borgiani, Paola


    Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening drug reactions involving skin and membranes mucous, which are associated with significant morbidity and mortality and triggered, especially by drug exposure. Different studies have demonstrated that drug response is a multifactorial character and that the interindividual variability in this response depends on both environmental and genetic factors. The last ones have a relevant significance. In fact, the identification of new specific genetic markers involved in the response to drugs, will be of great utility to establish a more personalized therapeutic approach and to prevent the appearance of these adverse reactions. In this review, we summarize recent progresses in the Pharmacogenetics studies related to Stevens-Johnson syndrome/toxic epidermal necrolysis reporting the major genetic factors identified in the last years as associated with the disease and highlighting the use of some of these genomic variants in the clinical practice.

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

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


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

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

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


    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.

  5. Hypertrophic scarring is associated with epidermal abnormalities : An immunohistochemical study

    Adriessen, MP; Niessen, FB; Van de Kerkhof, PC; Schalkwijk, J


    The role of epidermal keratinocytes in the early phases of normal unimpaired wound healing has been studied extensively. However, little is known about the cell biological processes in the epidermis and the basal membrane zone during the later phases of dermal matrix formation and remodelling of the

  6. Hypertrophic scarring is associated with epidermal abnormalities : An immunohistochemical study

    Adriessen, MP; Niessen, FB; Van de Kerkhof, PC; Schalkwijk, J


    The role of epidermal keratinocytes in the early phases of normal unimpaired wound healing has been studied extensively. However, little is known about the cell biological processes in the epidermis and the basal membrane zone during the later phases of dermal matrix formation and remodelling of the

  7. Exudative epidermitis in pigs caused by toxigenic Staphylococcus chromogenes

    Andresen, Lars Ole; Ahrens, Peter; Daugaard, Lise


    Staphylococcus chromogenes is closely related to Staphylococcus hyicus, which is recognised as the causative agent of exudative epidermitis (EE) in pigs. S. chromogenes is part of the normal skin flora of pigs, cattle and poultry and has so far been considered non-pathogenic to pigs. A strain of S...

  8. The epidermal growth factor receptor pathway in chronic kidney diseases

    Harskamp, Laura R.; Gansevoort, Ron T.; Goor, van Harry; Meijer, Esther


    The epidermal growth factor receptor (EGFR) pathway has a critical role in renal development, tissue repair and electrolyte handling. Numerous studies have reported an association between dysregulation of this pathway and the initiation and progression of various chronic kidney diseases such as diab

  9. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis ...

    drugs, and sometimes by infections.1 They are characterised by widespread ... infections by. Mycoplasma pneumoniae and the herpes simplex virus.⁵ .... Figure 2: Toxic Epidermal Necrolysis due first line treatment for TB – note greater than 30 % skin ... Human intravenous immune globulin (IVIg) has been used for both ...

  10. Epidermal growth factor receptor: Target for delivery and silencing

    Santos Oliveira, S.


    Epidermal growth factor receptor in cancer therapy Recently, cancer research has been able to identify molecular targets that are specific for (or highly expressed by) cancer cells. These molecular targets serve as models for the development of rationally designed anticancer drugs that target import

  11. Epidermal hydration levels in rosacea patients improve after minocycline therapy.

    Ní Raghallaigh, S


    Patients with rosacea frequently report increased skin sensitivity, with features suggestive of an abnormal stratum corneum (SC) permeability barrier. Sebum, pH and hydration levels influence epidermal homeostasis. The correlation of the change in these parameters with clinically effective treatment has not been previously analysed.

  12. Glucocorticoid receptor, but not mineralocorticoid receptor, mediates cortisol regulation of epidermal ionocyte development and ion transport in zebrafish (danio rerio.

    Shelly Abad Cruz

    Full Text Available Cortisol is the major endogenous glucocorticoid (GC both in human and fish, mediated by corticosteroid receptors. Due to the absence of aldosterone production in teleost fish, cortisol is also traditionally accepted to function as mineralocorticoid (MC; but whether it acts through the glucocorticoid receptor (GR or the mineralocorticoid receptor (MR remains a subject of debate. Here, we used loss-of-function and rescue assays to determine whether cortisol affects zebrafish epidermal ionocyte development and function via the GR and/or the MR. GR knockdown morphants displayed a significant decrease in the major ionocytes, namely Na(+-K(+-ATPase-rich cells (NaRCs and H(+-ATPase-rich cells (HRCs, as well as other cells, including epidermal stem cells (ESCs, keratinocytes, and mucus cells; conversely, cell numbers were unaffected in MR knockdown morphants. In agreement, GR morphants, but not MR morphants, exhibited decreased NaRC-mediated Ca(2+ uptake and HRC-mediated H(+ secretion. Rescue via GR capped mRNA injection or exogenous cortisol incubation normalized the number of epidermal ionocytes in GR morphants. We also provide evidence for GR localization in epidermal cells. At the transcript level, GR mRNA is ubiquitously expressed in gill sections and present in both NaRCs and HRCs, supporting the knockdown and functional assay results in embryo. Altogether, we have provided solid molecular evidence that GR is indeed present on ionocytes, where it mediates the effects of cortisol on ionocyte development and function. Hence, cortisol-GR axis performs the roles of both GC and MC in zebrafish skin and gills.

  13. Prognostic model for brain metastases from lung adenocarcinoma identified with epidermal growth factor receptor mutation status.

    Li, Hongwei; Wang, Weili; Jia, Haixia; Lian, Jianhong; Cao, Jianzhong; Zhang, Xiaqin; Song, Xing; Jia, Sufang; Li, Zhengran; Cao, Xing; Zhou, Wei; Han, Songye; Yang, Weihua; Xi, Yanfen; Lian, Shenming


    Several indices have been developed to predict survival of brain metastases (BM) based on prognostic factors. However, such models were designed for general brain metastases from different kinds of cancers, and prognostic factors vary between cancers and histological subtypes. Recently, studies have indicated that epidermal growth factor receptor (EGFR) mutation status may be a potential prognostic biological factor in BM from lung adenocarcinoma. Thus, we sought to define the role of EGFR mutation in prognoses and introduce a prognostic model specific for BM from lung adenocarcinoma. Data of 256 patients with BM from lung adenocarcinoma identified with EGFR mutations were collected. Independent prognostic factors were confirmed using a Cox regression model. The new prognostic model was developed based on the results of multivariable analyses. The score of each factor was calculated by six-month survival. Prognostic groups were divided into low, medium, and high risk based on the total scores. The prediction ability of the new model was compared to the three existing models. EGFR mutation and Karnofsky performance status were independent prognostic factors and were thus integrated into the new prognostic model. The new model was superior to the three other scoring systems regarding the prediction of three, six, and 12-month survival by pairwise comparison of the area under the curve. Our proposed prognostic model specific for BM from lung adenocarcinoma incorporating EGFR mutation status was valid in predicting patient survival. Further verification is warranted, with prospective testing using large sample sizes. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  14. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells.

    Klar, Agnieszka S; Güven, Sinan; Biedermann, Thomas; Luginbühl, Joachim; Böttcher-Haberzeth, Sophie; Meuli-Simmen, Claudia; Meuli, Martin; Martin, Ivan; Scherberich, Arnaud; Reichmann, Ernst


    The major problem in skin grafting is that tissue-engineered skin grafts after their transplantation are initially entirely dependent on diffusion. Since this process is slow and inefficient, nutrients, growth factors, and oxygen will insufficiently be supplied and the regenerating graft will undergo a physiological crisis, resulting in scar-like dermal structures and shrinkage. The tissue-engineering of a vascular network in human dermo-epidermal skin substitutes (DESS) is a promising approach to overcome this limitation. Here we report, for the first time, on the use of the adipose stromal vascular fraction (SVF)-derived endothelial cell population to tissue-engineer DESS containing a highly efficient capillary plexus. To develop vascular networks in vitro, we employed optimized 3D fibrin or collagen type I hydrogel systems. Upon transplantation onto immune-deficient rats, these pre-formed vascular networks anastomosed to the recipient's vasculature within only four days. As a consequence, the neo-epidermis efficiently established tissue homeostasis, the dermis underwent almost no contraction, and showed sustained epidermal coverage in vivo. Overall, the here described rapid and efficient perfusion of SVF-based skin grafts opens new perspectives for the treatment of hitherto unmet clinical needs in burn/plastic surgery and dermatology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands.

    Lasse Henriksen

    Full Text Available 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.

  16. Epidermal psoriasiform hyperplasia, an unrecognized sign of folliculitis decalvans: A histological study of 26 patients.

    Matard, Bruno; Cavelier-Balloy, Benedicte; Reygagne, Pascal


    Follicular hyperkeratosis along with hyperplasia of the follicular and interfollicular epithelia are major histopathological characteristics of hidradenitis suppurativa (HS). The presence of an occasional thickening of lesional skin in some folliculitis decalvans (FD) patients and histological similarities between FD and HS led us to look for epidermal hyperplasia and follicular hyperkeratosis in FD patients. We performed a retrospective histological analysis of 26 patients with FD. We sought to find out whether the presence of hyperplasia of the interfollicular epidermis and of the follicular epithelia could be verified in FD, with reference to the work of von Laffert et al. concerning HS. The main quantitative and qualitative data were: follicular hyperkeratosis (77%), hyperplasia of the interfollicular epidermis (92%) with a psoriasiform aspect (88%), atrophy of the follicular epithelia (85%), plasma cells in infiltrate (92%) in large quantities (42%), follicular microcysts (60%), atrophy of the sebaceous glands (85%) and polytrichia (54%). Epidermal hyperplasia, sometimes psoriasiform and follicular microcysts, are significant histological signs of FD, which have been ignored until now although they seem very common. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Revisiting epidermal growth factor receptor in glioblastoma multiforme: Does it play a role in response to therapy?

    Priyanka Soni


    Full Text Available Background and Aim: Glioblastoma multiforme (GBM are the most aggressive class of cancer of central nervous system with hallmark characteristics that include rampant proliferation, necrosis, and endothelial proliferation. Epidermal growth factor receptor (EGFR has been implicated as the primary contributor to glioblastoma initiation and succession. The present study was designed to evaluate EGFR protein expression in GBM as predictor of response to therapy and survival. Materials and Methods: Epidermal growth factor receptor was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots (10 high-power fields. The study group comprised of 35 cases of GBM. All cases underwent surgical resection and subsequently underwent radiotherapy (n = 17 or radiotherapy with adjuvant temozolomide chemotherapy (n = 18. Immediate response to therapy was assessed at 3 months using World Health Organization response evaluation criteria in solid tumors criteria and cases followed up for survival. Results: Twenty-four cases (68.6% expressed EGFR while 11/35 (31.4% cases were negative. Response to therapy was evident in 21/35 cases (60.0% and 14/35 were (40.0% nonresponders. Mean EGFR protein expression in responders was 37.23 ± 33.70 and in nonresponders was 59.5 ± 39.46 (P = 0.542. The percentage of responders which were EGFR negative was 72.7% and while response in EGFR positive cases was observed in 54.2%. Mean survival in EGFR positive and negative GBM was 394.37 ± 189.11 and 420.54 ± 191.23 days, respectively. Conclusion: The EGFR negative cases appear to respond better to therapy, however, the difference is not statistically significant (P = 0.298. Further, EGFR protein expression does not play a definitive role in predicting survival. This is an original study evaluating EGFR in terms of therapeutic response.

  18. Squamous cell carcinoma arising from an epidermal cyst in the thumb

    Sakamoto, Akio; Shiba, Eisuke; Hisaoka, Masanori


    Introduction Squamous cell carcinoma arising from an epidermal cyst is rare, and the most frequently affected region is the head and neck. Presentation of case A 41-year-old man noticed swelling and a small ulceration in the thumb pulp. A lesion with a 2-cm diameter was simply resected based on a diagnosis of infected epidermal cyst. Pathological diagnosis of the resected material was squamous cell carcinoma arising from an epidermal cyst. Consequent amputation was performed. Discussion and conclusion The clinical symptoms of squamous cell carcinoma arising from an epidermal cyst can mimic those of an infected epidermal cyst. The current report facilitates awareness of such disease. PMID:25912006

  19. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

    Olsen, Peter Skov; Boesby, S.; Kirkegaard, P.;


    growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had......The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal...

  20. Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

    Fraunholz, Ingeborg, E-mail: [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Rödel, Franz; Kohler, Daniela [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Diallo-Georgiopoulou, Margarita [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Department of Radiation Oncology, Klinikum Offenbach, Offenbach/Main (Germany); Distel, Luitpold [Department of Radiation Oncology, Friedrich Alexander University, Erlangen (Germany); Falk, Stefan [Pathology Associates, Frankfurt/Main (Germany); Rödel, Claus [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany)


    Purpose: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Methods and Materials: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Results: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Conclusion: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.

  1. Lapatinib plus trastuzumab in pretreated human epidermal growth factor receptor 2-positive metastatic breast cancer

    Miguel J Sotelo


    Full Text Available Background: Dual human epidermal growth factor receptor 2 (HER2 blockade has been preclinically and clinically assessed in HER2-overexpressing metastatic breast cancer (mBC with encouraging results. Patients and Methods: This is a descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing mBC from two centers. The primary endpoints were to assess objective response rate (ORR and toxicity. The secondary endpoints were to assess progression-free survival (PFS and overall survival. Results: A total of 23 HER2-positive mBC patients previously treated with trastuzumab received a trastuzumab plus lapatinib based therapy. Chemotherapy (CT was added to the dual HER2 blockade treatment in 13 patients (56%, whereas hormonotherapy (HT was added in 8 patients (35% and 2 patients (9% received lapatinib plus trastuzumab without any other agent. ORR was 22% (5/23 and 39% (9/23 of patients had stable disease. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, whereas PFS in patients with HT was 2 months. Grade ≥ 3 adverse events were diarrhea (26% and hand-and-foot syndrome (9%. Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible in pretreated HER2-positive mBC patients.

  2. Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

    Jorge, S.E.D.C.; Kobayashi, S.S.; Costa, D.B. [Harvard Medical School, Beth Israel Deaconess Medical Center, Department of Medicine, Division of Hematology/Oncology, Boston, MA (United States)


    Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

  3. Epidermal growth factor receptor (EGFR mutations in lung cancer: preclinical and clinical data

    S.E.D.C. Jorge


    Full Text Available Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC, the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs. Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686 and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

  4. Expression Levels of Some Antioxidant and Epidermal Growth Factor Receptor Genes in Patients with Early-Stage Non-Small Cell Lung Cancer

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio


    This study was aimed at: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others. PMID:20700416

  5. Expression levels of some antioxidant and epidermal growth factor receptor genes in patients with early-stage non-small cell lung cancer.

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio


    THIS STUDY WAS AIMED AT: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others.

  6. The Kubilius government survives major opposition attack / Rokas M. Tracevskis

    Tracevskis, Rokas M.


    Leedu transpordi- ja kommunikatsiooniministri Eligijus Masiulise umbusaldus ebaõnnestus. Peaminister Andrius Kubilius leiab, et opositsioon soovis sellega tema juhitud valitsust kukutada, kuna Eligijus Masiulist peetakse valitsuse parimaks ministriks. Euroopa Parlamendi liikme Roland Paksase poolt alustatud kohtuasjast

  7. The Kubilius government survives major opposition attack / Rokas M. Tracevskis

    Tracevskis, Rokas M.


    Leedu transpordi- ja kommunikatsiooniministri Eligijus Masiulise umbusaldus ebaõnnestus. Peaminister Andrius Kubilius leiab, et opositsioon soovis sellega tema juhitud valitsust kukutada, kuna Eligijus Masiulist peetakse valitsuse parimaks ministriks. Euroopa Parlamendi liikme Roland Paksase poolt alustatud kohtuasjast

  8. Transcription factor Ctip2 controls epidermal lipid metabolism and regulates expression of genes involved in sphingolipid biosynthesis during skin development

    Wang, Zhixing; Kirkwood, Jay S.; Taylor, Alan W.; Stevens, Jan F.; Leid, Mark; Ganguli-Indra, Gitali; Indra, Arup K.


    The stratum corneum is composed of protein-enriched corneocytes embedded in an intercellular matrix of nonpolar lipids organized as lamellar layers and give rise to epidermal permeability barrier (EPB). EPB defects play an important role in the pathophysiology of skin diseases such as eczema. The transcriptional control of skin lipid metabolism is poorly understood. We have discovered that mouse lacking a transcription factor COUP-TF interacting protein 2 (Ctip2) exhibit EPB defects including altered keratinocyte terminal differentiation, delayed skin barrier development and interrupted neutral lipid distribution in the epidermis. We adapted herein a targeted lipidomic approach using mass spectrometry, and have determined that Ctip2−/− mice (germline deletion of Ctip2 gene) display altered composition of major epidermal lipids such as ceramides and sphingomyelins compared to wildtype at different stages of skin development. Interestingly, expressions of several genes involved in skin sphingolipid biosynthesis and metabolism were altered in mutant skin. Ctip2 was found to be recruited to the promoter region of a subset of those genes, suggesting their possible direct regulation by Ctip2. Our results confirm an important role of Ctip2 in regulating skin lipid metabolism and indicate that profiling of epidermal sphingolipid could be useful for designing effective strategies to improve barrier dysfunctions. PMID:23096701

  9. Effects of essential fatty acid deficiency on epidermal O-acylsphingolipids and transepidermal water loss in young pigs.

    Melton, J L; Wertz, P W; Swartzendruber, D C; Downing, D T


    Linoleate-rich O-acylglucosylceramides and acylceramides are thought to be of major significance for the physical structure and function of the epidermal permeability barrier. In the present investigation, the effects of a linoleate-free diet on O-acylsphingolipids and their associated functions were investigated. Starting at 5 days of age, male pigs were fed diets containing 12% of either lard or hydrogenated coconut oil. Transepidermal water loss was measured with an electrolytic water analyzer at weekly intervals. Pigs were killed at intervals, and epidermal lipids were isolated and analyzed. Fatty acid compositions were determined by gas-liquid chromatography (GLC). Within 2-3 weeks, pigs on the diet containing coconut oil began to display biochemical and physiological symptoms of essential fatty acid deficiency. Within 2 months, this group had extremely scaly skin and transepidermal water loss was elevated to five times that of controls. The progressive increase in transepidermal water loss correlated with replacement of linoleate by oleate in both acylceramide and acylglucosylceramide. The formation of lamellar granules and intercellular lipid sheets in the stratum corneum was not impaired in essential fatty acid deficiency as judged by electron microscopy. These results suggest that the linoleic acid normally found in the O-acylsphingolipids is not essential for formation of the epidermal membrane system. Rather, it appears that the nature of the ester-linked fatty acid in the O-acylsphingolipids regulates the permeability of this membrane system.

  10. Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis.

    Conrad, Curdin; Boyman, Onur; Tonel, Giulia; Tun-Kyi, Adrian; Laggner, Ute; de Fougerolles, Antonin; Kotelianski, Victor; Gardner, Humphrey; Nestle, Frank O


    Psoriasis is a common T cell-mediated autoimmune inflammatory disease. We show that blocking the interaction of alpha1beta1 integrin (VLA-1) with collagen prevented accumulation of epidermal T cells and immunopathology of psoriasis. Alpha1beta1 integrin, a major collagen-binding surface receptor, was exclusively expressed by epidermal but not dermal T cells. Alpha1beta1-positive T cells showed characteristic surface markers of effector memory cells and contained high levels of interferon-gamma but not interleukin-4. Blockade of alpha1beta1 inhibited migration of T cells into the epidermis in a clinically relevant xenotransplantation model. This was paralleled by a complete inhibition of psoriasis development, comparable to that caused by tumor necrosis factor-alpha blockers. These results define a crucial role for alpha1beta1 in controlling the accumulation of epidermal type 1 polarized effector memory T cells in a common human immunopathology and provide the basis for new strategies in psoriasis treatment focusing on T cell-extracellular matrix interactions.

  11. The epidermal growth factor system in Caenorhabditis elegans.

    Moghal, Nadeem; Sternberg, Paul W


    The single known epidermal growth factor-like growth factor and single epidermal growth factor receptor in Caenorhabditis elegans mediate two types of processes, each via a distinct signal transduction pathway. Several instances of cell fate specification during organogenesis require the RAS-MAP kinase pathway, as well as multiple nuclear factors. By contrast, appropriate myoepithelial contractions during ovulation involve IP3-mediated signal transduction. Positive modulators of the RAS pathway include KSR, SUR-8, phosphatase PP2A, and a zinc cation diffusion facilitator. Negative regulators of the RAS pathway include homologs of CBL, GAP-1, ACK, and MAP kinase phosphatase, while negative regulators of the IP3 pathway are enzymes that modify IP3. In addition to its stimulation of RAS activity, the GRB2 homolog SEM-5 acts negatively on both signaling pathways, as does the Ack-related kinase ARK-1.

  12. Toxic epidermal necrolysis secondary to ceftriaxone use: A case report

    Mustafa İçer


    Full Text Available Toxic epidermal necrolysis (TEN is a rare, life-threatening condition that is usually associated with medication use and characterized by separation of epidermis and dermis and a scalded skin appearance. A 71-year-old man presented to emergency department with fever, malaise, and hyperemic skin eruptions and bullae. Skin lesions covered more than 70% of total body surface area. Nikolsky sign was positive. He had been begun ceftriaxone for pneumonia before. TEN was considered as the initial diagnosis; the medication he used was stopped, appropriate supportive treatment was begun, and the patient was admitted to intensive care unit. He was discharged on 8th day after skin epithelization occurred. Toxic epidermal necrolysis is a highly fatal syndrome, in which early diagnosis, stopping the offensive drug, and administering appropriate supportive treatment are important components of the management.

  13. Leaf Epidermal Cells: A Trap for Lipophilic Xenobiotics

    Zhiqian Liu


    Plant surfaces are covered by a layer of cuticle, which functions as a natural barrier to protect plants from mechanical damage, desiccation, and microbial invasion. Results presented in this report show that the epicuticular wax and the cuticle of plant leaves also play an important role in resisting xenobiotic invasion.Although the epicuticular wax is impermeableto hydrophilic xenobiotics, the cuticle not only restricts the penetration of hydrophilic compounds into leaf cells, but also traps lipophilic ones. The role of the epidermal cells of plant leaves in resisting xenobiotic invasion has been neglected until now. The present study shows, for the first time, that the epidermal cells may reduce or retard the transport of lipophilic xenobiotics into the internal tissues through vacuolar sequestration. Although the guard cells appear to be an easy point of entry for xenobiotics, only a very small proportion of xenobiotics present on the leaf surface actually moves into leaf tissues via the guard cells.

  14. Hollow silicon microneedle array based trans-epidermal antiemetic patch for efficient management of chemotherapy induced nausea and vomiting

    Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit


    Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.

  15. Rapid and dynamic subcellular reorganization following mechanical stimulation of Arabidopsis epidermal cells mimics responses to fungal and oomycete attack

    Takemoto Daigo


    Full Text Available Abstract Background Plant cells respond to the presence of potential fungal or oomycete pathogens by mounting a basal defence response that involves aggregation of cytoplasm, reorganization of cytoskeletal, endomembrane and other cell components and development of cell wall appositions beneath the infection site. This response is induced by non-adapted, avirulent and virulent pathogens alike, and in the majority of cases achieves penetration resistance against the microorganism on the plant surface. To explore the nature of signals that trigger this subcellular response and to determine the timing of its induction, we have monitored the reorganization of GFP-tagged actin, microtubules, endoplasmic reticulum (ER and peroxisomes in Arabidopsis plants – after touching the epidermal surface with a microneedle. Results Within 3 to 5 minutes of touching the surface of Arabidopsis cotyledon epidermal cells with fine glass or tungsten needles, actin microfilaments, ER and peroxisomes began to accumulate beneath the point of contact with the needle. Formation of a dense patch of actin was followed by focusing of actin cables on the site of contact. Touching the cell surface induced localized depolymerization of microtubules to form a microtubule-depleted zone surrounding a dense patch of GFP-tubulin beneath the needle tip. The concentration of actin, GFP-tubulin, ER and peroxisomes remained focused on the contact site as the needle moved across the cell surface and quickly dispersed when the needle was removed. Conclusion Our results show that plant cells can detect the gentle pressure of a microneedle on the epidermal cell surface and respond by reorganizing subcellular components in a manner similar to that induced during attack by potential fungal or oomycete pathogens. The results of our study indicate that during plant-pathogen interactions, the basal defence response may be induced by the plant's perception of the physical force exerted by the

  16. Tumor epidermóide intramedular: relato de caso

    Rocha Júnior Marco Antônio


    Full Text Available É relatado um caso raro de tumor epidermóide intramedular, estendendo-se entre os níveis da segunda e quarta vértebras torácicas, em uma paciente de 15 anos do sexo feminino, tratado cirurgicamente com sucesso. São discutidos o quadro clínico e a etiopatogenia e é feita breve revisão da literatura.

  17. A review of toxic epidermal necrolysis management in Japan

    Yuri Kinoshita


    Full Text Available Toxic epidermal necrolysis (TEN is a severe adverse drug reaction characterized by necrosis of the epidermis. Its incidence is approximately 1 per million a year and average mortality rate is high at 25–50%. TEN has a flu-like prodrome, followed by atypical, targetoid erythematous or purpuric macules on the skin. These macules coalesce to form flaccid blisters that slough off as areas of epidermal necrosis. Drugs such as allopurinol, sulfonamides, and carbamazepine are the most common causes. The human leukocyte antigen (HLA-B*15:02 in Asians being administered carbamazepine and the HLA-B*58:01 antigen in patients of all ethnicities being administered allopurinol are known to be high-risk factors. Rapid diagnosis, discontinuation of the causative drug, and supportive treatment are essential for better prognosis and improvement of sequelae. Till now, systemic corticosteroids and intravenous immunoglobulins have been used as the most common active interventions; however, no gold standard has been established. In Japan, physicians follow a unique diagnostic criteria and treatment guideline to improve the diagnosis rate and streamline treatments. This may be a contributing factor for the lower mortality rate (14.3%. The efficacy of systemic corticosteroids, immunoglobulins, and plasmapheresis may have been beneficial as well. In Japan, TEN is defined as an epidermal detachment of over 10% of the body surface area (BSA, while the globally accepted definition established by Bastuji-Garin describes it as an epidermal detachment of over 30% of the BSA. In Japanese individuals, HLA-A*02:06, HLA-A*02:07, HLA-A*31:01 and HLA-B*51:01 may be linked to higher risks of TEN.

  18. Phospholipase C-epsilon regulates epidermal morphogenesis in Caenorhabditis elegans.

    Rafael P Vázquez-Manrique


    Full Text Available Migration of cells within epithelial sheets is an important feature of embryogenesis and other biological processes. Previous work has demonstrated a role for inositol 1,4,5-trisphosphate (IP(3-mediated calcium signalling in the rearrangement of epidermal cells (also known as hypodermal cells during embryonic morphogenesis in Caenorhabditis elegans. However the mechanism by which IP(3 production is stimulated is unknown. IP(3 is produced by the action of phospholipase C (PLC. We therefore surveyed the PLC family of C. elegans using RNAi and mutant strains, and found that depletion of PLC-1/PLC-epsilon produced substantial embryonic lethality. We used the epithelial cell marker ajm-1::gfp to follow the behaviour of epidermal cells and found that 96% of the arrested embryos have morphogenetic defects. These defects include defective ventral enclosure and aberrant dorsal intercalation. Using time-lapse confocal microscopy we show that the migration of the ventral epidermal cells, especially of the leading cells, is slower and often fails in plc-1(tm753 embryos. As a consequence plc-1 loss of function results in ruptured embryos with a Gex phenotype (gut on exterior and lumpy larvae. Thus PLC-1 is involved in the regulation of morphogenesis. Genetic studies using gain- and loss-of-function alleles of itr-1, the gene encoding the IP(3 receptor in C. elegans, demonstrate that PLC-1 acts through ITR-1. Using RNAi and double mutants to deplete the other PLCs in a plc-1 background, we show that PLC-3/PLC-gamma and EGL-8/PLC-beta can compensate for reduced PLC-1 activity. Our work places PLC-epsilon into a pathway controlling epidermal cell migration, thus establishing a novel role for PLC-epsilon.

  19. Phospholipase C-epsilon regulates epidermal morphogenesis in Caenorhabditis elegans.

    Rafael P Vázquez-Manrique


    Full Text Available Migration of cells within epithelial sheets is an important feature of embryogenesis and other biological processes. Previous work has demonstrated a role for inositol 1,4,5-trisphosphate (IP(3-mediated calcium signalling in the rearrangement of epidermal cells (also known as hypodermal cells during embryonic morphogenesis in Caenorhabditis elegans. However the mechanism by which IP(3 production is stimulated is unknown. IP(3 is produced by the action of phospholipase C (PLC. We therefore surveyed the PLC family of C. elegans using RNAi and mutant strains, and found that depletion of PLC-1/PLC-epsilon produced substantial embryonic lethality. We used the epithelial cell marker ajm-1::gfp to follow the behaviour of epidermal cells and found that 96% of the arrested embryos have morphogenetic defects. These defects include defective ventral enclosure and aberrant dorsal intercalation. Using time-lapse confocal microscopy we show that the migration of the ventral epidermal cells, especially of the leading cells, is slower and often fails in plc-1(tm753 embryos. As a consequence plc-1 loss of function results in ruptured embryos with a Gex phenotype (gut on exterior and lumpy larvae. Thus PLC-1 is involved in the regulation of morphogenesis. Genetic studies using gain- and loss-of-function alleles of itr-1, the gene encoding the IP(3 receptor in C. elegans, demonstrate that PLC-1 acts through ITR-1. Using RNAi and double mutants to deplete the other PLCs in a plc-1 background, we show that PLC-3/PLC-gamma and EGL-8/PLC-beta can compensate for reduced PLC-1 activity. Our work places PLC-epsilon into a pathway controlling epidermal cell migration, thus establishing a novel role for PLC-epsilon.

  20. Epidermal growth factor receptor expression in urinary bladder cancer

    Dayalu S.L. Naik


    Full Text Available Objective : To evaluate the expression pattern of epidermal growth factor receptor (EGFR in urinary bladder cancer and its association with human epidermal growth factor receptor 2 (HER2, epidermal growth factor (EGF, interleukin-6 (IL-6, and high risk human papilloma virus (HPV types 16 and 18. Materials and Methods : Thirty cases of urothelial carcinoma were analyzed. EGFR, HER2, EGF, and IL-6 expressions in the tissue were evaluated by immunohistochemical staining. For HPV, DNA from tissue samples was extracted and detection of HPV was done by PCR technique. Furthermore, evaluation of different intracellular molecules associated with EGFR signaling pathways was performed by the western blot method using lysates from various cells and tissues. Results : In this study, the frequencies of immunopositivity for EGFR, HER2, EGF, and IL-6 were 23%, 60%, 47%, and 80%, respectively. No cases were positive for HPV-18, whereas HPV-16 was detected in 10% cases. Overall, expression of EGFR did not show any statistically significant association with the studied parameters. However, among male patients, a significant association was found only between EGFR and HER2. Conclusions : Overexpression of EGFR and/or HER2, two important members of the same family of growth factor receptors, was observed in a considerable proportion of cases. Precise knowledge in this subject would be helpful to formulate a rational treatment strategy in patients with urinary bladder cancer.

  1. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review

    Anthony Wong

    Full Text Available SUMMARY Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These pathologies are considered a hypersensitivity reaction and can be triggered by drugs, infections and malignancies. The drugs most often involved are allopurinol, some antibiotics, including sulfonamides, anticonvulsants such as carbamazepine, and some non-steroid anti-inflammatory drugs (NSAIDs. Necrosis of keratinocytes is manifested clinically by epidermal detachment, leading to scalded skin appearance. The rash begins on the trunk with subsequent generalization, usually sparing the palmoplantar areas. Macular lesions become purplish, and epidermal detachment occurs, resulting in flaccid blisters that converge and break, resulting in extensive sloughing of necrotic skin. Nikolsky's sign is positive in perilesional skin. SJS and TEN are considered to be two ends of the spectrum of one disease, differing only by their extent of skin detachment. Management of patients with SJS or TEN requires three measures: removal of the offending drug, particularly drugs known to be high-risk; supportive measures and active interventions. Early diagnosis of the disease, recognition of the causal agent and the immediate withdrawal of the drug are the most important actions, as the course of the disease is often rapid and fatal.

  2. Morphometry of primary and secondary epidermal laminae in equine hoof

    Luana S. Oliveira


    Full Text Available We studied the length of primary and secondary epidermal laminae of the toe and the lateral and medial quarters of horses, distributed into proximal, middle and distal thirds of the hooves. Eight limbs from adult crossbred horses, four females and four males, used to pull carts without pedal conditions. Fragments were taken from different regions of the hooves and subjected to conventional histological techniques. The samples were stained with hematoxylin-eosin and analyzed by light microscopy. The primary epidermal laminae were higher in the hooves of forelimbs compared to hindlimbs in the proximal and middle thirds and the regions of the medial quarter and toe. The secondary laminae were higher in forelimb of the middle third and medial quarter. Comparing the length of the epidermal laminae between hoof parts, it was seen that the primary laminae are lower in the proximal third and higher in the toe, while the secondary laminae are lower in the proximal third and medial quarter. The results suggested that the morphology of the laminae in the different regions of the hooves is influenced through the work performed by the animal, as well as through the different distribution of forces.

  3. Characterization of powdered epidermal vaccine delivery with multiphoton microscopy

    Mulholland, William J [PowderJect Centre for Gene and Drug delivery Research, Department of Engineering Science, University of Oxford OX2 6PE (United Kingdom); Kendall, Mark A F [PowderJect Centre for Gene and Drug delivery Research, Department of Engineering Science, University of Oxford OX2 6PE (United Kingdom); White, Nick [Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE (United Kingdom); Bellhouse, Brian J [PowderJect Centre for Gene and Drug delivery Research, Department of Engineering Science, University of Oxford OX2 6PE (United Kingdom)


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

  4. The circadian molecular clock creates epidermal stem cell heterogeneity.

    Janich, Peggy; Pascual, Gloria; Merlos-Suárez, Anna; Batlle, Eduard; Ripperger, Jürgen; Albrecht, Urs; Cheng, Hai-Ying M; Obrietan, Karl; Di Croce, Luciano; Benitah, Salvador Aznar


    Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.

  5. A highly pathogenic strain of Staphylococcus sciuri caused fatal exudative epidermitis in piglets.

    Shixi Chen

    Full Text Available Staphylococcus sciuri are important human pathogens responsible for endocarditis, peritonitis, septic shock, urinary tract infection, pelvic inflammatory disease and wound infections. However, little information is known regarding the pathogenicity of S. sciuri to animals. From the pericardial fluid of a diseased piglet with exudative epidermitis (EE, we isolated a strain of Staphylococcus in pure culture. Surprisingly, this isolate was a member of S. sciuri rather than S. hyicus as identified by its biochemical traits and also by analysis of 23S ribosomal DNA using Internal Transcribed Spacer PCR. In addition, inoculation of newborn piglets with 1x10(10 CFU of the isolate by oral feeding or intra-muscular injection successfully reproduced EE in piglets, which suggested that the oral intake of the pathogen by the animals is one of the major routes of exposure. These unexpected findings prioritized S. sciuri as important zoonotic agents, which may have ramifications for human medicine.

  6. Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis

    Jiang, Xinnong; Multhaupt, Hinke; Chan, En


    As a major heparan sulfate proteoglycan (PG) in basement membranes, perlecan has been linked to tumor invasion, metastasis, and angiogenesis. Here we produced epidermal tumors in immunocompromised rats by injection of mouse RT101 tumor cells. Tumor sections stained with species-specific perlecan...... antibodies, together with immunoelectron microscopy, showed that perlecan distributed around blood vessels was of both host and tumor cell origin. Tumor-derived perlecan was also distributed throughout the tumor matrix. Blood vessels stained with rat-specific PECAM-1 antibody showed their host origin. RT101...... cells also expressed two other basement membrane heparan sulfate PGs, agrin and type XVIII collagen. Antisense targeting of perlecan inhibited tumor cell growth in vitro, while exogenous recombinant perlecan, but not heparin, restored the growth of antisense perlecan-expressing cells, suggesting...

  7. The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer

    Atmaca Akin


    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is a potential target of anticancer therapy in gastric cancer. However, its prognostic role in metastatic gastric or gastroesophageal junction (GE cancer has not been established yet. Methods EGFR status was analyzed by immunohistochemistry (IHC in paraffin-embedded samples from 357 patients who received chemotherapy in 4 first-line trials. Automated RNA extraction from paraffin and RT-quantitative PCR were additionally used to evaluate EGFR mRNA expression in 130 patients. Results EGFR protein expression (any grade and overexpression (3+ were observed in 43% and 11% of patients, respectively. EGFR positivity correlated with intestinal type histology (p = 0.05, but not with other clinicopathologic characteristics. Median follow-up was 18.2 months. Median overall survival (OS was similar in patients with EGFR positive vs. those with EGFR negative tumors, regardless whether positivity was defined as ≥1+ (10.6 vs. 10.9 months, p = 0.463 or as 3+ (8.6 vs. 10.8 months, p = 0.377. The multivariate analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12, p = 0.247. There were also no significant differences in overall survival when patients were categorized according to median (p = 0.116 or quartile (p = 0.767 distribution of EGFR mRNA gene expression. Similar distributions of progression-free survival according to EGFR status were observed. Conclusions Unlike different cancer types where EGFR-positive disease is associated with an adverse prognostic value, EGFR positivity is not prognostic of patient outcome in metastatic gastric or GE cancer.

  8. Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies

    Clemmensen, Anders; Thomassen, Mads; Clemmensen, Ole;


    To obtain a separation of the epidermal and dermal compartments to examine compartment specific biological mechanisms in the skin, we incubated 4 mm human skin punch biopsies in ammonium thiocyanate. We wanted to test (i) the histological quality of the dermo-epidermal separation obtained...... was not always histologically well-defined (i.e. occurred partly intra-epidermally), but also varied between subjects. Consequently, curettage along the dermal surface of the biopsy was added to the procedure. This modified method resulted in an almost perfect separation of the epidermal and dermal compartments...... and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly prove...

  9. Genética Molecular das Epidermólises Bolhosas Molecular Genetics of Epidermolysis Bullosa

    Hiram Larangeira de Almeida Jr


    Full Text Available O estudo das alterações moleculares das epidermólises bolhosas tem contribuído para que se compreenda melhor essas enfermidades. Na epidermólise bolhosa simples a maioria dos casos está associada com alteração nas citoqueratinas basais 5 (gen KRT5 e 14 (gen KRT14, o que modifica o citoesqueleto na camada basal da epiderme, levando à degeneração dessa camada, formando bolha intra-epidérmica. Mutações na plectina (gen PLEC1, componente da placa interna do hemidesmossoma, levam também à clivagem intra-epidérmica. Na epidermólise bolhosa juncional vários gens estão envolvidos, em decorrência da complexidade da zona da membrana basal, todos levando ao descolamento dos queratinócitos basais na lâmina lúcida, pela disfunção da aderência entre esses e a lâmina densa. Alterações na laminina 5 (gens LAMA3, LAMB3 e LAMC2, integrina alfa6beta4 (gens ITGA6 e ITGB4 e colágeno XVII (gen COL17A1 foram descritas. Por fim, na epidermólise bolhosa distrófica apenas um gen está mutado, alterando o colágeno VII (gen COL7A1, principal componente das fibrilas ancorantes, produzindo clivagem abaixo da lâmina densa, variando fenotipicamente de acordo com a conseqüência da mutação. Outra aplicação importante dessas informações refere-se ao diagnóstico pré-natal, com a perspectiva no futuro da terapia gênica.New data regarding the molecular aspects of the heterogeneous group of epidermolysis bullosa has brought some important information about its pathogenesis. In epidermolysis bullosa simplex the majority of mutations are localized in the genes of the basal cytokeratin 5 (gene KRT5 and 14 (gene KRT14, cytolysis at this layer with intraepidermal blister is seen under light microscopy. Mutations of plectin (gene PLEC1, a protein found in the inner hemidesmosomal plaque, leads also to intraepidermal blisters. In junctional epidermolysis bullosa many proteins from the basal membrane zone are involved, such as laminin 5 (genes

  10. Epidermal growth factor receptor gene amplification and protein expression in glioblastoma multiforme: prognostic significance and relationship to other prognostic factors.

    Layfield, Lester J; Willmore, Carlynn; Tripp, Sheryl; Jones, Claudia; Jensen, Randy L


    Epidermal growth factor receptor (EGFR) overexpression occurs in a significant percentage of cases of glioblastoma multiforme (GBM), and amplification has been found in approximately 40% of these neoplasms. Controversy exists as to the prognostic significance of EGFR gene amplification: some reports have indicated that amplification is associated with a poor prognosis, while other authors have reported no relationship between gene amplification and prognosis. Some reports have found a poor prognosis to be associated with amplification of the EGFR gene in patients of all ages with GBM, while other authors have found EGFR amplification to be an independent predictor of prolonged survival in patients with GBM who are older than 60 years of age. The authors studied a series of 34 specimens (32 patients) with histologically proven GBM by immunohistochemistry for the presence of EGFR overexpression and by fluorescence in situ hybridization (FISH) for gene amplification of the EGFR gene. Results of these studies and data on patient age, sex, functional status, therapy, and survival were correlated to determine which variables were predictive of survival. p53 expression was also determined by immunohistochemistry and correlated with the other variables and survival.

  11. Human papillomavirus E6/E7 oncogenes promote mouse ear regeneration by increasing the rate of wound re-epithelization and epidermal growth.

    Valencia, Concepción; Bonilla-Delgado, José; Oktaba, Katarzyna; Ocádiz-Delgado, Rodolfo; Gariglio, Patricio; Covarrubias, Luis


    Mammals have limited regeneration capacity. We report here that, in transgenic mice (Tg(bK6-E6/E7)), the expression of the E6/E7 oncogenes of human papilloma virus type 16 (HPV16) under the control of the bovine keratin 6 promoter markedly improves the mouse's capacity to repair portions of the ear after being wounded. Increased repair capacity correlates with an increased number of epidermal proliferating cells. In concordance with the expected effects of the E6 and E7 oncogenes, levels of p53 decreased and those of p16 in epidermal cells increased. In addition, we observed that wound re-epithelization proceeded faster in transgenic than in wild-type animals. After the initial re-epithelization, epidermal cell migration from the intact surrounding tissue appears to be a major contributor to the growing epidermis, especially in the repairing tissue of transgenic mice. We also found that there is a significantly higher number of putative epidermal stem cells in Tg(bK6-E6/E7) than in wild-type mice. Remarkably, hair follicles and cartilage regenerated within the repaired ear tissue, without evidence of tumor formation. We propose that the ability to regenerate ear portions is limited by the capacity of the epidermis to repair itself and grow.

  12. Predicting survival and morbidity-free survival to very old age

    R.S. Newson (Rachel); J.C.M. Witteman (Jacqueline); O.H. Franco (Oscar); B.H.Ch. Stricker (Bruno); M.M.B. Breteler (Monique); A. Hofman (Albert); H.W. Tiemeier (Henning)


    textabstractAs life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify factors that increase the chance of survival free of major morbidities. As such, the current study assessed 45 common diseas

  13. Epidermal cyst of the breast simulating a benign solid mass: A case report

    Chung, Sun Yang; Shim, Jeong Yeon [Pochon CHA University College of Medicine, Pochon (Korea, Republic of); Oh, Ki Keun [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    Epidermal cysts are benign epithelial cysts occurring within the skin. Epidermal cysts are not uncommonly found in the skin of the breast, but rare in the nipple and subareolar area. There have been only a few radiologic reports. We report a case of a 40 year old woman with an incidentally discovered epidermal cyst, located in the subareolar area, and this lesion was radiologically resembled a benign solid mass.

  14. Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

    Kamstrup, M.; Faurschou, A.; Gniadecki, R.


    in the basal layer of the interfollicular epidermis and in the bulge region of the hair follicle play a critical role for normal tissue maintenance. In wound healing, multipotent epidermal stem cells contribute to re-epithelization. It is possible that defects in growth control of either epidermal stem cells......In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...




    Full Text Available Epidermal cysts involving head and neck are uncommon representing around 7% of all epidermal cysts in the body . Sublingual cysts are still uncommon (1 . 5 - 2% usually presenting in young adults in 2 nd or 3 rd decade of life . An epidermal cyst presenting at birth in sublingual position is extr emely rare . A large sublingual epidermal cyst in a newborn baby girl , which is causing breathing and swallowing difficulties leading to hypoxia in supine position and continuous drooling of saliva with inability to close the mouth , is reported . Successful excision of the cyst without rupture by transoral route under general anesthesia is performed at 24 hours of life .

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

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


    ... and urogenital systems. We describe a patient with an extensive epidermal nevus associated with various organ abnormalities, particularly polyostotic fibrous dysplasia, central nervous system lipoma, and aplasia cutis...

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

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


    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.

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

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


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

  19. Inhibition of JNK promotes differentiation of epidermal keratinocytes.

    Gazel, Alix; Banno, Tomohiro; Walsh, Rebecca; Blumenberg, Miroslav


    In inflamed tissue, normal signal transduction pathways are altered by extracellular signals. For example, the JNK pathway is activated in psoriatic skin, which makes it an attractive target for treatment. To define comprehensively the JNK-regulated genes in human epidermal keratinocytes, we compared the transcriptional profiles of control and JNK inhibitor-treated keratinocytes, using DNA microarrays. We identified the differentially expressed genes 1, 4, 24, and 48 h after the treatment with SP600125. Surprisingly, the inhibition of JNK in keratinocyte cultures in vitro induces virtually all aspects of epidermal differentiation in vivo: transcription of cornification markers, inhibition of motility, withdrawal from the cell cycle, stratification, and even production of cornified envelopes. The inhibition of JNK also induces the production of enzymes of lipid and steroid metabolism, proteins of the diacylglycerol and inositol phosphate pathways, mitochondrial proteins, histones, and DNA repair enzymes, which have not been associated with differentiation previously. Simultaneously, basal cell markers, including integrins, hemidesmosome and extracellular matrix components, are suppressed. Promoter analysis of regulated genes finds that the binding sites for the forkhead family of transcription factors are over-represented in the SP600125-induced genes and c-Fos sites in the suppressed genes. The JNK-induced proliferation appears to be secondary to inhibition of differentiation. The results indicate that the inhibition of JNK in epidermal keratinocytes is sufficient to initiate their differentiation program and suggest that augmenting JNK activity could be used to delay cornification and enhance wound healing, whereas attenuating it could be a differentiation therapy-based approach for treating psoriasis.

  20. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

    Young-Su Yi


    Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a secreted protein found in vertebrates and was initially discovered as a critical component of the mil...

  1. An immunologic approach to induction of epidermal growth factor deficiency

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier;


    Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish an in vivo model with a state of EGF deficiency......(-9) mol/L. The antibodies recognized purified EGF from the submandibular glands (6 kD) and from urine (45 kD) and further native EGF in saliva and urine. The cross-reactivity toward transforming growth factor-alpha was below 3%. Binding of EGF by antibodies inhibited its binding to the EGF...

  2. Cyclophosphamide in the treatment of toxic epidermal necrolysis.

    Frangogiannis, N G; Boridy, I; Mazhar, M; Mathews, R; Gangopadhyay, S; Cate, T


    A patient with non-small cell lung carcinoma and recent radiotherapy for brain metastases developed toxic epidermal necrolysis (TEN) shortly after therapy with phenytoin was initiated for a seizure. Exfoliation progressed to involve 90% of her body surface despite treatment with high-dose corticosteroids for 5 days, but sloughing and systemic toxicity ceased within 2 days of initiating therapy with intravenous cyclophosphamide (300 mg/day). Reepithelialization rapidly followed. This experience and the reports of others suggest that intravenous cyclophosphamide is helpful in the treatment of TEN.

  3. Targeting the epidermal growth factor receptor in solid tumor malignancies

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S


    The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have...... been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...

  4. Simultaneous occurrence of toxic epidermal necrolysis and neuroleptic malignant syndrome

    Muhammed K


    Full Text Available Toxic epidermal necrolysis (TEN is an acute life-threatening blistering disease characterized by involvement of the skin, multiple mucous membranes and internal organs. It is most commonly precipitated by the administration of medications like anticonvulsants. Neuroleptic malignant syndrome (NMS is a rare complication of neuroleptic therapy characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction. An 18-year-old girl presenting with simultaneous appearance of TEN and NMS following anti-psychotic drugs given for bipolar mood disorder, is reported for the rare association and her complete recovery.

  5. Immunohistochemical localization of epidermal growth factor in rat and man

    Poulsen, Steen Seier; Nexø, Ebba


    Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands...... is well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands...

  6. Cephalosporin Induced Toxic Epidermal Necrolysis and Subsequent Penicillin Drug Exanthem

    Amanda Lam; Inderpal Randhawa; William Klaustermeyer


    Background: Drug hypersensitivity is classically divided into IgE mediated and non-IgE mediated disease. We report a rare case of consequent IgE mediated and non-IgE mediated reactions within the beta lactam class of antibiotics. Case Summary: An 84-year-old man developed toxic epidermal necrolysis (TEN) due to ceftriaxone, a third generation cephalosporin, involving 72% of the body surface area. The patient recovered but within weeks subsequently developed an acute IgE mediated allergic r...

  7. Toxic Epidermal Necrolysis induced by rarely implicated drugs

    Sujit Rajagopalan


    Full Text Available Toxic Epidermal Necrolysis (TEN and Steven-Johnson Syndrome (SJS are serious disorders commonly caused as idiosyncratic reactions to drugs, the most common ones being oxicams, anticonvulsants, allopurinol, and sulfonamides. We present a case of TEN in a patient who developed the lesions after ingesting multiple drugs including paracetamol, metoclopramide, antihistamines, and multivitamins. These drugs have rarely been implicated in this disorder. The suspected drugs in this case were paracetamol and metoclopramide. However, the role of other drugs could not be ruled out definitely. The patient was managed with antibiotics, corticosteroids, and parenteral fluids and recovered well.

  8. Acyl-CoA binding protein and epidermal barrier function

    Bloksgaard, Maria; Neess, Ditte; Færgeman, Nils J


    enzymatic systems; however, the precise function remains unknown. ACBP is expressed at relatively high levels in the epidermis, particularly in the suprabasal layers, which are highly active in lipid synthesis. Targeted disruption of the ACBP gene in mice leads to a pronounced skin and fur phenotype, which...... levels of non-esterified very long chain fatty acids in the stratum corneum of ACBP(-/-) mice. Here we review the current knowledge of ACBP with special focus on the function of ACBP in the epidermal barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis...

  9. Multinationals and plant survival

    Bandick, Roger


    The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

  10. Toxic epidermal necrolysis due to concomitant use of valproic asid and lamotrigine

    Hamdi Özcan


    Full Text Available Toxic epidermal necrolysis (TEN is a rare but life-threatening acute mucacutaneous hypersensitivity reaction, usually related to medications. Concomitant use of lamotrigine and valproic asid can cause this serious reaction. A 36 year-old-man admitted to emergency department with high fever, burning sensation at eyes, oral and genital mucous erosions, generalized rush and weakness. He had been taking valproic asid, olanzapine, and sertraline for bipolar affective disorder. Lamotrigine 25 mg/day treatment was added his treatment protocol 15 days ago before the rush and lamotgine dose was increased 50 mg/day 10 days later. The patient was diagnosed as TEN caused by concomitant use of valproic asid and lamotrigine. The patient followed up and treated at burn unit with intravenous immunoglobulin, corticosteroid and antibiotics. Concomitant use of valproic asid and lamotrigine increases the frequency of adverse reaction. TEN may cause serious complications and mortality. The patients with TEN should be followed by a multi-disciplinary team. Early determination of complications and suitable management can increase survival.

  11. Epidermal growth factor receptor inhibitor protects against abdominal aortic aneurysm in a mouse model.

    Obama, Takashi; Tsuji, Toshiyuki; Kobayashi, Tomonori; Fukuda, Yamato; Takayanagi, Takehiko; Taro, Yoshinori; Kawai, Tatsuo; Forrester, Steven J; Elliott, Katherine J; Choi, Eric; Daugherty, Alan; Rizzo, Victor; Eguchi, Satoru


    Angiotensin II (Ang II) has been implicated in the development of abdominal aortic aneurysm (AAA). In vascular smooth muscle cells (VSMC), Ang II activates epidermal growth factor receptor (EGFR) mediating growth promotion. We hypothesized that inhibition of EGFR prevents Ang II-dependent AAA. C57BL/6 mice were co-treated with Ang II and β-aminopropionitrile (BAPN) to induce AAA with or without treatment with EGFR inhibitor, erlotinib. Without erlotinib, 64.3% of mice were dead due to aortic rupture. All surviving mice had AAA associated with EGFR activation. Erlotinib-treated mice did not die and developed far fewer AAA. The maximum diameters of abdominal aortas were significantly shorter with erlotinib treatment. In contrast, both erlotinib-treated and non-treated mice developed hypertension. The erlotinib treatment of abdominal aorta was associated with lack of EGFR activation, endoplasmic reticulum (ER) stress, oxidative stress, interleukin-6 induction and matrix deposition. EGFR activation in AAA was also observed in humans. In conclusion, EGFR inhibition appears to protect mice from AAA formation induced by Ang II plus BAPN. The mechanism seems to involve suppression of vascular EGFR and ER stress.

  12. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

    Ping Zhao


    Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

  13. Epidermal Homeostasis and Radiation Responses in a Multiscale Tissue Modeling Framework

    Hu, Shaowen; Cucinotta, Francis A.


    The surface of skin is lined with several thin layers of epithelial cells that are maintained throughout life time by a small population of stem cells. High dose radiation exposures could injure and deplete the underlying proliferative cells and induce cutaneous radiation syndrome. In this work we propose a multiscale computational model for skin epidermal dynamics that links phenomena occurring at the subcellular, cellular, and tissue levels of organization, to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis. Incorporating experimentally measured histological and cell kinetic parameters, we obtain results of population kinetics and proliferation indexes comparable to observations in unirradiated and acutely irradiated swine experiments. At the sub-cellular level, several recently published Wnt signaling controlled cell-cycle models are applied and the roles of key components and parameters are analyzed. Based on our simulation results, we demonstrate that a moderate increase of proliferation rate for the survival proliferative cells is sufficient to fully repopulate the area denuded by high dose radiation, as long as the integrity of underlying basement membrane is maintained. Our work highlights the importance of considering proliferation kinetics as well as the spatial organization of tissues when conducting in vivo investigations of radiation responses. This integrated model allow us to test the validity of several basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and enhance our understanding of the pathophysiological effects of ionizing radiation on skin.

  14. Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations

    Lamond NW


    Full Text Available Nathan WD Lamond, Tallal YounisDepartment of Medicine, Dalhousie University at the Queen Elizabeth II Health Sciences Centre, Halifax, NS, CanadaAbstract: In the absence of specific therapy, the 15%–20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2 protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin, the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta, a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab's clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab’s incorporation into clinical practice.Keywords: HER2/neu, clinical trials, drug development, novel therapies, targeted anticancer therapy

  15. The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity.

    Cheng-Gang Zou

    Full Text Available The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca(2+ release. Ca(2+ mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS. ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca(2+-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response.

  16. Human epidermal growth factor receptor 2 expression in mixed gastric carcinoma.

    Wang, Yang-Kun; Chen, Zhong; Yun, Tian; Li, Cong-Yang; Jiang, Bo; Lv, Xue-Xia; Chu, Guang-Hui; Wang, Su-Nan; Yan, Hui; Shi, Lei-Feng


    To investigate human epidermal growth factor receptor 2 (HER2) amplification and protein expression in mixed gastric carcinoma. Fluorescence in situ hybridization and immunohistochemistry were used to detect HER2 amplification and protein expression in 277 cases of mixed gastric carcinoma. Protein staining intensity was rate as 1+, 2+, or 3+. Of the 277 cases, 114 (41.2%) expressed HER2 protein. HER2 3+ staining was observed in 28/277 (10.1%) cases, 2+ in 37/277 (13.4%) cases, and 1+ in 49/277 (17.7%) cases. A HER2 amplification rate of 17% was detected, of which 25/28 (89.3%) were observed in the HER2 3+ staining group, 17/37 (45.9%) in 2+, and 5/49 (10.2%) in 1+. Of the 47 patients with HER2 amplification who received chemotherapy plus trastuzumab, 22 demonstrated median progression-free and overall survivals of 9.1 mo and 16.7 mo, respectively, which were significantly better than those achieved with chemotherapy alone (5.6 mo and 12.1 mo, respectively) in 19 previously treated patients (Ps gastric carcinoma displays high heterogeneity. Relatively quantitative parameters are needed for assessing the level of HER2 amplification and protein expression.

  17. Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers

    Nathan Simon


    Full Text Available Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have progressed to human trials. This review summarizes much of the past and current work in the development of immunotoxins for targeting EGFR-driven cancers.

  18. Differential gene expression profiling of human epidermal growth factor receptor 2-overexpressing mammary tumor

    Yan Wang; Haining Peng; Yingli Zhong; Daiqiang Li; Mi Tang; Xiaofeng Ding; Jian Zhang


    Human epidermal growth factor receptor 2 (HER2) is highly expressed in approximately 30% of breast cancer patients,and substantial evidence supports the relationship between HER2 overexpression and poor overall survival. However,the biological function of HER2 signaltransduction pathways is not entirely clear. To investigate gene activation within the pathways, we screened differentially expressed genes in HER2-positive mouse mammary tumor using two-directional suppression subtractive hybridization combined with reverse dot-blotting analysis. Forty genes and expressed sequence tags related to transduction, cell proliferation/growth/apoptosis and secreted/extracellular matrix proteins were differentially expressed in HER2-positive mammary tumor tissue. Among these, 19 were already reported to be differentially expressed in mammary tumor, 11 were first identified to be differentially expressed in mammary tumor in this study but were already reported in other tumors, and 10 correlated with other cancers. These genes can facilitate the understanding of the role of HER2 signaling in breast cancer.

  19. Advances in Variations of Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor-2 Status in Metastatic Breast Cancer

    Yuan Yuan; Zhang Lili


    Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.

  20. Bioengineering of cultured epidermis from adult epidermal stem cells using Mebio gel sutable as autologous graft material

    Lakshmana K Yerneni


    Full Text Available Closure of burn wound is the primary requirement in order to reduce morbidity and mortality that are otherwise very high due to non-availability of permanent wound covering materials. Sheets of cultured epidermis grown from autologous epidermal keratinocyte stem cells are accepted world over as one of the best wound covering materials. In a largely populated country like ours where burn casualties occur more frequently due to inadequate safety practices, there is a need for indigenous research inputs to develop such methodologies. The technique to culturing epidermal sheets in vitro involves the basic Reheinwald-Green method with our own beneficial inputs. The technique employs attenuated 3T3 cells as feeders for propagating keratinocyte stem cells that are isolated from the epidermis of an initial skin biopsy of about 5 cm2 from the patient. The cultures are then maintained in Dulbecco's modified Eagle's medium strengthened with Ham's F12 formula, bovine fetal serum and various specific growth-promoting agents and factors in culture flasks under standard culture conditions. The primary cultures thus established would be serially passaged to achieve the required expansion. Our major inputs are into the establishment of (1 an efficient differential trypsinization protocol to isolate large number epidermal keratinocytes from the skin biopsy, (2 a highly specific, unique and foolproof attenuation protocol for 3T3 cells and (3 a specialized and significant decontamination protocol. The fully formed epidermal sheet as verified by immuno-histochemical and light & electron microscopic studies, is lifted on to paraffin gauze by incubating in a neutral protease. The graft is then ready to be transported to the operating theatre for autologous application. We have a capability of growing cultured epidermal sheets sufficient enough to cover 40 per cent burn wound in 28 days. The preliminary small area clinical applications undertaken so far revealed

  1. Bacterial survival in Martian conditions

    D'Alessandro, Giuseppe Galletta; Giulio Bertoloni; Maurizio


    We shortly discuss the observable consequences of the two hypotheses about the origin of life on Earth and Mars: the Lithopanspermia (Mars to Earth or viceversa) and the origin from a unique progenitor, that for Earth is called LUCA (the LUCA hypothesis). To test the possibility that some lifeforms similar to the terrestrial ones may survive on Mars, we designed and built two simulators of Martian environments where to perform experiments with different bacterial strains: LISA and mini-LISA. Our LISA environmental chambers can reproduce the conditions of many Martian locations near the surface trough changes of temperature, pressure, UV fluence and atmospheric composition. Both simulators are open to collaboration with other laboratories interested in performing experiments on many kind of samples (biological, minerals, electronic) in situations similar to that of the red planet. Inside LISA we have studied the survival of several bacterial strains and endospores. We verified that the UV light is the major re...

  2. Mitochondrial tolerance to single and repeat exposure to simulated sunlight in human epidermal and dermal skin cells.

    Kelly, J; Murphy, J E J


    Sunlight represents the primary threat to mitochondrial integrity in skin given the unique nature of the mitochondrial genome and its proximity to the electron transport chain. The accumulation of mitochondrial DNA (mtDNA) mutations is a key factor in many human pathologies and this is linked to key roles of mitochondrial function in terms of energy production and cell regulation. The main objective of this study was to evaluate solar radiation induced changes in mitochondrial integrity, function and dynamics in human skin cells using a Q-Sun solar simulator to deliver a close match to the intensity of summer sunlight. Spontaneously immortalised human skin epidermal keratinocytes (HaCaT) and Human Dermal Fibroblasts (HDFn) were divided into two groups. Group A were irradiated once and Group B twice 7days apart and evaluated using cell survival, viability and mitochondrial membrane potential (MMP) and mass at 1, 4 and 7days post one exposure for Group A and 1, 4, 7 and 14days post second exposure for Group B. Viability and survival of HaCaT and HDFn cells decreased after repeat exposure to Simulated Sunlight Irradiation (SSI) with no recovery. HDFn cells showed no loss in MMP after one or two exposures to SSI compared to HaCaT cells which showed a periodic loss of MMP after one exposure with a repeat exposure causing a dramatic decrease from which cells did not recover. Mitochondrial Mass in exposed HDFn cells was consistent with control after one or two exposures to SSI; however mitochondrial mass was significantly decreased in HaCaT cells. Data presented here suggests that mitochondria in epidermal cells are more sensitive to sunlight damage compared to mitochondria in dermal cells, despite their origin, confirming a skin layer specific sensitivity to sunlight, but not as expected. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Differential regulation of human Eag1 channel expression by serum and epidermal growth factor in lung and breast cancer cells

    Acuña-Macías I


    Full Text Available Isabel Acuña-Macías,1 Eunice Vera,1 Alma Yolanda Vázquez-Sánchez,1 María Eugenia Mendoza-Garrido,2 Javier Camacho1 1Department of Pharmacology, 2Department of Physiology, Biophysics and Neurosciences, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico Abstract: Oncogenic ether à-go-go-1 (Eag1 potassium channels are overexpressed in most primary human solid tumors. Low oxygen and nutrient/growth factor concentrations play critical roles in tumorigenesis. However, the mechanisms by which tumor cells survive and proliferate under growth factor-depleted conditions remain elusive. Here, we investigated whether serum-deprived conditions and epidermal growth factor (EGF regulate Eag1 expression in human lung and breast cancer cells. The human cancer cell lines A549 and MCF-7 (from the lungs and breast, respectively were obtained from the American Type Culture Collection and cultured following the manufacturer’s recommendations. Eag1 gene and protein expression were studied by real-time PCR and immunocytochemistry, respectively. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay, and ERK1/2 phosphorylation was investigated by Western blot. Serum-deprived conditions increased Eag1 mRNA and protein expression in both cell lines. This Eag1 upregulation was prevented by EGF and the ERK1/2 inhibitor U0126 in only lung cancer cells; vascular endothelial growth factor did not prevent Eag1 upregulation. Our results suggest that Eag1 may act as a survival and mitogenic factor under low-serum and nutrient conditions and may be a clinical target during the early stages of tumor development. Keywords: lung cancer, serum deprivation, ether à-go-go, potassium channels, EGF, epidermal growth factor, ERK 1/2

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

    Chiou-Mei Lee

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

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

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


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

  6. MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations.

    Nybakken, Grant E; Sargen, Michael; Abraham, Ronnie; Zhang, Paul J; Ming, Michael; Xu, Xiaowei


    Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.

  7. Upregulation of epidermal growth factor receptor 4 in ora leukoplakia

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


    In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ ErbB 1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP), The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

  8. Extraordinarily Stretchable All-Carbon Collaborative Nanoarchitectures for Epidermal Sensors

    Cai, Yichen


    Multifunctional microelectronic components featuring large stretchability, high sensitivity, high signal-to-noise ratio (SNR), and broad sensing range have attracted a huge surge of interest with the fast developing epidermal electronic systems. Here, the epidermal sensors based on all-carbon collaborative percolation network are demonstrated, which consist 3D graphene foam and carbon nanotubes (CNTs) obtained by two-step chemical vapor deposition processes. The nanoscaled CNT networks largely enhance the stretchability and SNR of the 3D microarchitectural graphene foams, endowing the strain sensor with a gauge factor as high as 35, a wide reliable sensing range up to 85%, and excellent cyclic stability (>5000 cycles). The flexible and reversible strain sensor can be easily mounted on human skin as a wearable electronic device for real-time and high accuracy detecting of electrophysiological stimuli and even for acoustic vibration recognition. The rationally designed all-carbon nanoarchitectures are scalable, low cost, and promising in practical applications requiring extraordinary stretchability and ultrahigh SNRs.

  9. Epidermolytic hyperkeratosis in inflammatory linear verrucous epidermal nevus

    Naser Tayyebi Meibodi


    Full Text Available Epidermolytic hyperkeratosis presents with perinuclear vacuolization of the keratinocytes in spinous and granular layers, keratinocytes with ill-defined limits, which leads to a reticulate appearance of the epidermis, an increased number of variously shaped and sized basophilic keratohyalin granules and the same sized eosinophilic trichohyalin granules, at any level of epidermis, mainly in the stratum granulosum, and compact hyperkeratosis. This minor reactive pathologic reaction pattern of skin is found in large variety of diseases. This paper is the first case report of such pattern in inflammatory linear verrucous epidermal nevus. Our case is of a 23-year-old man with pruritic verrucous lesions of trunk and extremities initiated since 13 years ago. Physical examination revealed white linear hyperkeratotic lesions, some of them on erythematous background and also classic epidermal nevus. No skeletal, ophthalmic, and nervous system involvement was detected. Microscopic study of pruritic verrucous lesions showed psoriasiform acanthosis, mild papillomatous, hyperkeratosis, and epidermolytic hyperkeratotic changes in hair follicles and acrosyrinx accompanied with moderate perivascular inflammation.

  10. Steven johnsons syndrome and toxic epidermal necrolysis: A review

    Sri ram Anne


    Full Text Available Toxic epidermal necrolysis (TEN and Stevens Johnson Syndrome (SJS are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the etiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP, disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS. Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy.

  11. Specific antibodies and sensitive immunoassays for the human epidermal growth factor receptors (HER2, HER3, and HER4).

    Broughton, Marianne Nordlund; Westgaard, Arne; Paus, Elisabeth; Øijordsbakken, Miriam; Henanger, Karoline J; Naume, Bjørn; Bjøro, Trine


    The use of trastuzumab in patients with breast cancer that overexpresses human epidermal growth factor receptor 2 has significantly improved treatment outcomes. However, a substantial proportion of this patient group still experiences progression of the disease after receiving the drug. Evaluation of the changes in expression of the human epidermal growth factor receptors could be of interest. Monoclonal antibodies against the extracellular domain of the human growth factor receptors, 2, 3, and 4, have been raised, and specific and sensitive immunoassays have been established. Sera from healthy individuals (Nordic Reference Interval Project and Database) were analyzed in the human epidermal growth factor receptor 2 assay (N = 805) and the human epidermal growth factor receptor 3 and 4 assays (N = 114), and reference limits were calculated. In addition, sera from 208 individual patients with breast cancer were tested in all three assays. Finally, the human epidermal growth factor receptor 2 assay was compared with a chemiluminescent immunoassay for serum human epidermal growth factor receptor 2/neu. Reference values were as follows: human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, human epidermal growth factor receptor 4, human epidermal growth factor receptor 2 and human epidermal growth factor receptor 3 serum levels between the patients with tissue human epidermal growth factor receptor 2-positive and tissue human epidermal growth factor receptor 2-negative ( p = 0.0026, p = 0.000011) tumors, but not in the serum levels of human epidermal growth factor receptor 4 ( p = 0.054). There was good agreement between the in-house human epidermal growth factor receptor 2 assay and the chemiluminescent immunoassay. Our new specific antibodies for all the three human epidermal growth factor receptors may prove valuable in the development of novel anti-human epidermal growth factor receptor targeted therapies with

  12. Proliferative activity of epidermal basal cells after wounding. AgNOR counts compared with bromodeoxyuridine reactivity in rats.

    Rebolledo Godoy, A P; Rebolledo Godoy, M; Meissner, C; Oehmichen, M


    Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation that can be demonstrated by a specific silver staining technique on paraffin-embedded sections. Wounding of skin induces proliferation of basal epidermal cells at the wound margin. The degree of proliferation depends on the survival time and can be measured by morphometric assessment of argyrophilic NORs (AgNORs). Following incision wounding of the pinnae, rats were allowed to survive for different intervals (7 rats per interval) up to 120 hours. Before each sacrifice, biopsies were taken and incubated in a bromodeoxyuridine (BrdU) solution, embedded in paraffin, and stained with an antibody against BrdU. At the same time morphometric analysis of AgNOR counts was performed on sections made from the same material. BrdU incorporating nuclei were assessed by simple counting, whereas morphometric analysis of AgNOR counts was computer aided. Both methods revealed an increase in the number of proliferating cells, a plateau phase being reached after about 36 hours, followed by a decline after about 70 hours. Both methods thus allowed a reliable temporal classification of the skin injury according to survival time. The molecular background of the AgNOR changes in relation to the proliferation of cellular elements is discussed in detail.

  13. Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation-positive non-small cell lung cancers: an update for recent advances in therapeutics.

    Chung, Clement


    The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations are in-frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and 20-40% of Asian patients with non-small cell lung cancer. T790M gene mutation at exon 20 is associated with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with afatinib is associated with improved progression-free survival compared to chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. However, despite a durable response of greater than a year, resistance to epidermal growth factor receptor tyrosine kinase inhibitors inevitably occurs. This mini-review describes the clinically relevant EGFR gene mutations and the efficacy/toxicity of small molecule epidermal growth factor receptor tyrosine kinase

  14. Transforming growth factor alpha and epidermal growth factor in laryngeal carcinomas demonstrated by immunohistochemistry

    Christensen, M E; Therkildsen, M H; Poulsen, Steen Seier


    Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF recep...

  15. The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

    Drzewiecki, K T; Piltz-Drzewiecka, J


    The quantitative evaluation of DOPA-positive epidermal melanocytes in 16 patients of Scandinavian origin showed both individual and regional differences in the melanocyte count. Our data is in agreement with other published studies. The distribution in the number of melanocytes varies significant...... concerning the presence of the epidermal melanin unit....

  16. Characterization of pigmented dermo-epidermal skin substitutes in a long-term in vivo assay.

    Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Klar, Agnieszka S; Widmer, Daniel S; Neuhaus, Kathrin; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst


    In our laboratory, we have been using human pigmented dermo-epidermal skin substitutes for short-term experiments since several years. Little is known, however, about the long-term biology of such constructs after transplantation. We constructed human, melanocyte-containing dermo-epidermal skin substitutes of different (light and dark) pigmentation types and studied them in a long-term animal experiment. Developmental and maturational stages of the epidermal and dermal compartment as well as signs of homoeostasis were analysed 15 weeks after transplantation. Keratinocytes, melanocytes and fibroblasts from human skin biopsies were isolated and assembled into dermo-epidermal skin substitutes. These were transplanted onto immuno-incompetent rats and investigated 15 weeks after transplantation. Chromameter evaluation showed a consistent skin colour between 3 and 4 months after transplantation. Melanocytes resided in the epidermal basal layer in physiological numbers and melanin accumulated in keratinocytes in a supranuclear position. Skin substitutes showed a mature epidermis in a homoeostatic state and the presence of dermal components such as Fibrillin and Tropoelastin suggested advanced maturation. Overall, pigmented dermo-epidermal skin substitutes show a promising development towards achieving near-normal skin characteristics and epidermal and dermal tissue homoeostasis. In particular, melanocytes function correctly over several months whilst remaining in a physiological, epidermal position and yield a pigmentation resembling original donor skin colour. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Growth activity of epidermal cells from different parts of human body

    CHAI Jia-ke; SHENG Zhi-yong; MA Zhong-feng; YANG Hong-ming; LIU Qiang; Liang Li-ming


    Background Most epidermal cells used in skin tissue engineering are obtained from the skins of fetuses or prepuces,which can not be widely used in culturing and transplanting autologous epidermis for patients with extensive burn wounds. To solve the problem, in this study, we cultured epidermal cells from different parts of human body in vitro, and detected their growth activity.Methods Normal epidermal cells obtained from the prepuce, scalp, and axilla of male patients, were cultured and passaged. Their growth characteristics including adherent rate and growth activity were compared. Data were analyzed by homogeneity test of variance.Results In primary culture, the growth of epidermal cells from the prepuce was significantly faster than that of the epidermal cells from the scalp and axilla. In the cells obtained from the prepuce, 80% confluence was achieved on day 12, while on day 16 and day 20 in the cells from the scalp and axilla, respectively. However, no significant difference was detected in their growth and proliferation in the second passage.Conclusions Although the growth of epidermal cells obtained from the scalp and axilla is slower than that from the prepuce in primary culture, stable cell line can be established and used in preparation of auto-epidermal grafts for patients with extensive burn wounds. Therefore, the scalp and axillary skin should be considered as important sources of epidermal cells other than the prepuce.

  18. Systemic epidermal nevus with involvement of the oral mucosa due to FGFR3 mutation

    Bygum, Anette; Fagerberg, Christina R; Clemmensen, Ole J


    Epidermal nevi (EN) represent benign congenital skin lesions following the lines of Blaschko. They result from genetic mosaicism, and activating FGFR3 and PIK3CA mutations have been implicated.......Epidermal nevi (EN) represent benign congenital skin lesions following the lines of Blaschko. They result from genetic mosaicism, and activating FGFR3 and PIK3CA mutations have been implicated....

  19. Growth activity of epidermal cells from different parts of human body.

    Chai, Jia-ke; Sheng, Zhi-yong; Ma, Zhong-feng; Yang, Hong-ming; Liu, Qiang; Liang, Li-ming


    Most epidermal cells used in skin tissue engineering are obtained from the skins of fetuses or prepuces, which can not be widely used in culturing and transplanting autologous epidermis for patients with extensive burn wounds. To solve the problem, in this study, we cultured epidermal cells from different parts of human body in vitro, and detected their growth activity. Normal epidermal cells obtained from the prepuce, scalp, and axilla of male patients, were cultured and passaged. Their growth characteristics including adherent rate and growth activity were compared. Data were analyzed by homogeneity test of variance. In primary culture, the growth of epidermal cells from the prepuce was significantly faster than that of the epidermal cells from the scalp and axilla. In the cells obtained from the prepuce, 80% confluence was achieved on day 12, while on day 16 and day 20 in the cells from the scalp and axilla, respectively. However, no significant difference was detected in their growth and proliferation in the second passage. Although the growth of epidermal cells obtained from the scalp and axilla is slower than that from the prepuce in primary culture, stable cell line can be established and used in preparation of auto-epidermal grafts for patients with extensive burn wounds. Therefore, the scalp and axillary skin should be considered as important sources of epidermal cells other than the prepuce.


    Mehmet Eren Yuksel


    Full Text Available Epidermal inclusion cysts are common benign cutaneous cysts which arise from hair follicles. These cysts usually present as asymptomatic, small, smooth, firm, round, slow growing swellings on hair bearing areas such as scalp, face, neck and trunk. Epidermal inclusion cysts are easily diagnosed by their clinical features. However, trichilemmal cyst, dermoid cyst, neurofibroma, hemangioma, lipoma and liposarcoma should also be kept in mind in differential diagnosis of cutaneous cystic lesions. As malignant transformation of epidermal inclusion cysts has been reported, histopathological evaluation of epidermal inclusion cysts is mandatory in order to rule out malignancy. Moreover, giant epidermal inclusion cysts with ulceration, rapid growth, resistance to treatment, recurrence and fistula drainage may have malignant potential. Therefore, epidermal cysts should be surgically removed. There are several different types of surgical techniques to remove cutaneous cysts. A proper surgical technique should facilitate the complete removal of the cyst wall to prevent recurrence. In addition, it should provide minimal scarring and a low wound infection rate. Epidermal inclusion cysts can be easily removed surgically with squeeze technique. In this technique, the cyst is squeezed out through a small incision using both index fingers. Thus, the cyst is not ruptured. The squeeze technique allows the cyst capsule to remain intact. Therefore, the risk of wound infection, recurrence and scar formation is minimized. Hereby, we present a 48-year-old male with multiple epidermal inclusion cysts on the scalp treated surgically with squeeze technique. 

  1. Distribution and number of epidermal growth factor receptors in skin is related to epithelial cell growth

    Green, M R; Basketter, D A; Couchman, J R


    Epidermal growth factor (EGF), a low-molecular-weight polypeptide (G. Carpenter and S. Cohen, 1979, Annu. Rev. Biochem. 48, 193-216), stimulates the proliferation and keratinisation of cultured embryonic epidermis (S. Cohen, 1965, Dev. Biol. 12, 394-407) and promotes epidermal growth, thickening,...

  2. Correlation between {sup 18}F Fluorodeoxyglucose uptake and epidermal growth factor receptor mutations in advanced lung cancer

    Choi, Yun Jung; Cho, Byoung Chul; Jeong, Youg Hyu; Seo, Hyo Jung; Kim, Hyun Jeong; Cho, Arthur; Lee, Jae Hoon; Yun, Mi Jin; Jeon, Tae Joo; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ., Health System, Seoul (Korea, Republic of)


    Mutations in the epidermal growth factor receptor (EGFR)gene have been identified as potential targets for the treatment and prognostic factors for non small cell lung cancer (NSCLC). We assessed the correlation between fluorodeoxyglucose (FDG) uptake and EGFR mutations, as well as their prognostic implications. A total of 163 patients with pathologically confirmed NSCLC were enrolled (99 males and 64 females; median age, 60 years). All patients underwent FDG positron emission tomography before treatment, and genetic studies of EGFR mutations were performed. The maximum standardized uptake value (SUVmax)of the primary lung cancer was measured and normalized with regard to liver uptake. The SUVmax between the wild type and EGFR mutant groups was compared. Survival was evaluated according to SUVmax and EGFR mutation status. EGFR mutations were found in 57 patients (60.8%). The SUVmax tended to be higher in wild type than mutant tumors, but was not significantly different (11.1{+-}5.7 vs. 9.8{+-}4.4, P=0.103). The SUVmax was significantly lower in patients with an exon 19 mutation than in those with either an exon 21 mutation or wild type (P=0.003 and 0.009, respectively). The EGFR mutation showed prolonged overall survival (OS) compared to wild type tumors (P=0.004). There was no significant difference in survival according to SUVmax. Both OS and progression free survival of patients with a mutation in exon 19 were significant longer than in patients with wild type tumors. In patients with NSCLC, a mutation in exon 19 was associated with a lower SUVmax and is a reliable predictor for good survival.

  3. Survivability in warship design

    Keuning, P.J.; Smit, C.S.


    The initiative taken by the AVT panel to organise this symposium on combat survivability is much welcomed. From our perspective, the possibilities for the survivability experts within NATO to exchange their research efforts have always been rather limited. This symposium under sponsorship of the AVT

  4. Survival in Extreme Conditions.

    Bloom, Martin; Halsema, James


    Explores the psychosocial and environmental configurations involved in the survival of 500 civilians in a Japanese internment camp in the Philippines during World War II. Although conditions were very harsh, the survival rate of this group was better than expected. Discusses available demographic, social organizational, and cultural information.…

  5. Survivability in warship design

    Keuning, P.J.; Smit, C.S.


    The initiative taken by the AVT panel to organise this symposium on combat survivability is much welcomed. From our perspective, the possibilities for the survivability experts within NATO to exchange their research efforts have always been rather limited. This symposium under sponsorship of the AVT

  6. The correlation between serum epidermal growth factor/testicular epidermal growth factor receptor and spermatogenesis in rat

    Peng Yi-feng; Bao Shi-hua; Xu Dong-liang; Zong Wan; Fang Xiang; Sheng Shi-le; Lu Ling-ming; Xu Guo-xiang; LU Ren-kang


    Objective: To investigate the correlation between epidermal growth factor (EGF)/testicular epidermal growth factor receptor (EGF-R) and spermatogenesis in rat.Methods: Forty mature male Spraque-Dauley (SD) rats were randomly assigned to four groups, ten rats in each: sham operation group (SOG), sialoadenectomy group (SG), sialoadeand blood and testes were obtained on the 48th day after the operation. Serum EGF concentrations were determined by radioimmunoassay (RIA), expression of EGF-R in testes was examined by the immunohistochemical method, and the spermatogenesis was pathologically checked.Results:Serum EGF levels in SG-EGFIand SG decreased significantly when compared with those of SOG (P<0.05 and P< 0.01, respectively). The testicular function of spermatogenesis showed a moderate to severe impairment in SG. The expression of EGF-R in Leydig cells decreased in SG (P< 0. 05). The two dosage groups of EGF replacement had different effects.There were no significant differences of EGF-R expression in testicular germ cells, Sertoli cells and Leydig cells in SOG, SG-EGFIand SG-EGFⅡ(P>0.05).Conclusion: EGF may play an important role in the regulation of spermatogenesis. Serum EGF concentration and high expression of EGF-R in Leydig cells have a positive correlation with spermatogenic function of the testes.

  7. Dissociation of Thermal Nociception and Epidermal Innervation in Streptozotocin-Diabetic Mice

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


    The quantification of epidermal innervation, which consists primarily of heat-sensitive C-fibers, is emerging as a tool for diagnosing and staging diabetic neuropathy. However, the relationship between changes in heat sensitivity and changes in epidermal innervation has not yet been adequately explored. Therefore, we assessed epidermal nerve fiber density and thermal withdrawal latency in the hind paw of Swiss Webster mice after two and four weeks of streptozotocin-induced diabetes. Thermal hypoalgesia developed after only two weeks of diabetes, but a measurable reduction in PGP9.5-immunoreactive epidermal nerve fiber density did not appear until four weeks. These data suggest that impaired epidermal nociceptor function contributes to early diabetes-induced thermal hypoalgesia prior to the loss of peripheral terminals. PMID:18619518

  8. Epidermal development in mammals: key regulators, signals from beneath, and stem cells.

    Liu, Shuang; Zhang, Huishan; Duan, Enkui


    Epidermis is one of the best-studied tissues in mammals that contain types of stem cells. Outstanding works in recent years have shed great light on behaviors of different epidermal stem cell populations in the homeostasis and regeneration of the epidermis as well as hair follicles. Also, the molecular mechanisms governing these stem cells are being elucidated, from genetic to epigenetic levels. Compared with the explicit knowledge about adult skin, embryonic development of the epidermis, especially the early period, still needs exploration. Furthermore, stem cells in the embryonic epidermis are largely unstudied or ambiguously depicted. In this review, we will summarize and discuss the process of embryonic epidermal development, with focuses on some key molecular regulators and the role of the sub-epidermal mesenchyme. We will also try to trace adult epidermal stem cell populations back to embryonic development. In addition, we will comment on in vitro derivation of epidermal lineages from ES cells and iPS cells.

  9. Epidermal cyst of the bony external auditory canal in an adult

    Ihshan Ali


    Full Text Available To present a rare case of epidermal cyst of the bony external auditory canal (EAC in an adult. Epidermal cyst of the bony EAC, although very rare, should be kept in the list of differential diagnosis of a skin-lined mass of the EAC. Epidermal cyst is very rare in the EAC. Only two cases of epidermoid cyst arising from the bony EAC are reported previously in English, but both were in pediatric age group. Epidermal cyst in EAC in adult patients may be confused with masses that are commonly seen, and these include osteomas, exostosis, ear polyps, carcinomas, etc. Epidermal cyst should be included in the differential diagnosis of a patient with an ear mass.

  10. Dermoscopy of verrucous epidermal nevus: large brown circles as a novel feature for diagnosis.

    Carbotti, Mattia; Coppola, Rosa; Graziano, Antonio; Verona Rinati, Maria; Paolilli, Francesco Luigi; Zanframundo, Salvatore; Panasiti, Vincenzo


    The epidermal nevus is a hamartomatous proliferation of the epithelium that can involve keratinocytes, sebaceous glands, the pilosebaceous unit, and eccrine or apocrine glands. It occurs in one in 1000 live births and most commonly presents as the verrucous type. Dermoscopy is a non-invasive technique commonly used to differentiate between melanocytic and non-melanocytic lesions. This study was performed to analyze dermoscopic aspects of verrucous epidermal nevi, which have not previously been described. Dermoscopic analyses of eight different verrucous epidermal nevi were conducted. Each lesion was excised, and its diagnosis was histopathologically confirmed. In non-melanocytic lesions, a new dermoscopic feature of large brown circles was observed. This characteristic is useful in the diagnosis of verrucous epidermal nevi. Large brown circles represent a specific dermoscopic feature for the diagnosis of verrucous epidermal nevus. © 2015 The International Society of Dermatology.

  11. Marketing child survival.

    Grant, J P


    Growth monitoring charts, packets of oral rehydration salts (ORS), and vaccines, are inexpensive, life-saving, growth-protecting technologies which can enable parents to protect their children against the worst effects of poverty. Similarly, a matrix of current and easily understandable information about pregnancy, breast feeding, weaning, feeding during and immediately after illness, child spacing, and preparing and using home-made oral rehydration solutions, also could empower parents to protect the lives and the health of their children. The question arises as to how can these technologies and this information be put at the disposal of millions of families in the low-income world. The initial task of the Child Survival and Development Revolution is the communication of what is now possible, yet little is known about how to communicate information whose principal value is to the poor. There are 2 large-scale precedents: the Green Revolution, which in many instances succeeded in putting into the hands of thousands of small and large farmers the techniques and the knowledge which enabled them to double and treble the yields from their lands; and the campaign to put the knowledge and the means of family planning at the disposal of many millions of people. There are 2 lessons to be learned from these precedents: they have shown that the way to promote a people's technology and to put information at the disposal of the majority is by mobilizing all possible resources and working through all possible channels both to create the demand and to meet it; and neither the Green Revolution nor the family planning movement rally took off until they were viewed as political and economic priorities and given the full support of the nation's political leadership. Nowhere are these 2 lessons more clearly illustrated than in present-day Indonesia. Because the campaign for family planning was given high personal and political priority by the President, and because 85% of all family

  12. Monosomy of Chromosome 10 Associated With Dysregulation of Epidermal Growth Factor Signaling in Glioblastomas

    Yadav, Ajay K.; Renfrow, Jaclyn J.; Scholtens, Denise M.; Xie, Hehuang; Duran, George E.; Bredel, Claudia; Vogel, Hannes; Chandler, James P.; Chakravarti, Arnab; Robe, Pierre A.; Das, Sunit; Scheck, Adrienne C.; Kessler, John A.; Soares, Marcelo B.; Sikic, Branimir I.; Harsh, Griffith R.; Bredel, Markus


    Context Glioblastomas—uniformly fatal brain tumors—often have both monosomy of chromosome 10 and gains of the epidermal growth factor receptor (EGFR) gene locus on chromosome 7, an association for which the mechanism is poorly understood. Objectives To assess whether coselection of EGFR gains on 7p12 and monosomy 10 in glioblastomas promotes tumorigenic epidermal growth factor (EGF) signaling through loss of the annexin A7 (ANXA7) gene on 10q21.1–q21.2 and whether ANXA7 acts as a tumor suppressor gene by regulating EGFR in glioblastomas. Design, Setting, and Patients Multidimensional analysis of gene, coding sequence, promoter methylation, messenger RNA (mRNA) transcript, protein data for ANXA7 (and EGFR), and clinical patient data profiles of 543 high-grade gliomas from US medical centers and The Cancer Genome Atlas pilot project (made public 2006–2008; and unpublished, tumors collected 2001–2008). Functional analyses using LN229 and U87 glioblastoma cells. Main Outcome Measures Associations among ANXA7 gene dosage, coding sequence, promoter methylation, mRNA transcript, and protein expression. Effect of ANXA7 haploinsufficiency on EGFR signaling and patient survival. Joint effects of loss of ANXA7 and gain of EGFR expression on tumorigenesis. Results Heterozygous ANXA7 gene deletion is associated with significant loss of ANXA7 mRNA transcript expression (P=1×10−15; linear regression) and a reduction (mean [SEM]) of 91.5% (2.3%) of ANXA7 protein expression compared with ANXA7 wild-type glioblastomas (P=.004; unpaired t test). ANXA7 loss of function stabilizes the EGFR protein (72%–744% increase in EGFR protein abundance) and augments EGFR transforming signaling in glioblastoma cells. ANXA7 haploinsufficiency doubles tumorigenic potential of glioblastoma cells, and combined ANXA7 knockdown and EGFR overexpression promotes tumorigenicity synergistically. The heterozygous loss of ANXA7 in≈75% of glioblastomas in the The Cancer Genome Atlas plus

  13. Scaling of stomatal size and density optimizes allocation of leaf epidermal space for gas exchange in angiosperms

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


    Stomata on plant leaves are key traits in the regulation of terrestrial fluxes of water and carbon. The basic morphology of stomata consists of a diffusion pore and two guard cells that regulate the exchange of CO2 and water vapour between the leaf interior and the atmosphere. This morphology is common to nearly all land plants, yet stomatal size (defined as the area of the guard cell pair) and stomatal density (the number of stomata per unit area) range over three orders of magnitude across species. Evolution of stomatal sizes and densities is driven by selection pressure on the anatomical maximum stomatal conductance (gsmax), which determines the operational range of leaf gas exchange. Despite the importance of stomata traits for regulating leaf gas exchange, a quantitative understanding of the relation between adaptation of gsmax and the underlying co-evolution of stomatal sizes and densities is still lacking. Here we develop a theoretical framework for a scaling relationship between stomatal sizes and densities within the constraints set by the allocation of epidermal space and stomatal gas exchange. Our theory predicts an optimal scaling relationship that maximizes gsmax and minimizes epidermal space allocation to stomata. We test whether stomatal sizes and densities reflect this optimal scaling with a global compilation of stomatal trait data on 923 species reflecting most major clades. Our results show optimal scaling between stomatal sizes and densities across all species in the compiled data set. Our results also show optimal stomatal scaling across angiosperm species, but not across gymnosperm and fern species. We propose that the evolutionary flexibility of angiosperms to adjust stomatal sizes underlies their optimal allocation of leaf epidermal space to gas exchange.

  14. Degenerative and regenerative changes in epidermal organ culture: a morphological study with reference to membrane-coating granules.

    Chapman, S J; Vickers, C F


    Membrane-coating granules (MCG) are poorly understood lamellate organelles unique to keratinized epithelia. This study provides data on a skin model for future in vitro investigations of MCG. Porcine ear epidermal organ cultures were used under standard cell culture conditions. This system was selected because it is easily established and, following a degenerative period in which MCG are lost, regenerates to form a highly differentiated epidermis. The epidermis appeared healthy during the first 2 d in vitro and contained MCG but lost keratohyalin granules (KHG). Overt degenerative changes were evident in the upper epidermis on Day 3, and MCG were now bloated. By Day 4 only one to three layers of viable undifferentiated cells remained. In the overlying necrotic epidermis MCG were rare, presumably due to the bursting of bloated MCG. Epidermal regeneration began around Day 5 and by Day 7 there were 8 to 13 layers, including a rudimentary parakeratotic stratum corneum (up to 4 layers). The stratum granulosum (two to three layers) now contained immature KHG and poorly lamellate MCG, but only amorphous material extracellularly. By Day 11 there were three to four layers of granular cells as in vivo, and an orthokeratotic stratum corneum (two to four layers). Improved cornification coincided with an increased number of mature KHG and cross-banded MCG, and lamellate MCG contents extracellularly. This model of epidermal regeneration will facilitate studies into the role played by MCG in keratinization because the epithelium initially lacked MCG but later expressed all the major morphologic features of epidermis. Furthermore the mechanisms by which MCG translocation and extrusion are effected may be probed by the inclusion of such agents as antimicrotubular drugs and calcium ionophores.

  15. Principais características clínicas de pacientes que sobrevivem 24 meses ou mais após uma hospitalização devido a descompensação cardíaca Major clinical characteristics of patients surviving 24 months or more after hospitalization due to decompensated heart failure

    Mucio Tavares de Oliveira Jr


    Full Text Available OBJETIVO: Estudar as principais características clínicas dos pacientes com insuficiência cardíaca sobreviventes há mais de 24 meses após hospitalização para compensação. MÉTODOS: Estudados 126 pacientes com insuficiência cardíaca, em classe funcional III ou IV, com idade média de 51,7 anos, a maioria homens (73%, com fração de ejeção (FE média de 0,36 e diâmetro diastólico (DD do VE de 7,13 cm. Avaliaram-se as principais características clínicas e laboratoriais e no seguimento identificaram-se 25 (19.8% pacientes que sobreviveram mais de 24 meses após a alta hospitalar. Compararam-se os dados dos sobreviventes (G1 aos dos que faleceram (G2 antes de 24 meses. RESULTADOS: No G1 encontraram-se níveis mais elevados do sódio sérico (138,3±3,4 vs 134,5±5,8 mEq/l; p=0,001, da pressão arterial (120,0 vs 96,7 mmHg; p=0,003 e da FE do VE (0,40±0,08 vs 0,34±0,09; p=0,004 e valores menores da uréia (59,8 vs 76,3 mg/dl; p=0,007, do tempo de protrombina (12,9 vs 14,8s; p=0,001, do DDVE (6,78±0,55 vs 7,22±0,91; p=0,003 e do diâmetro do AE (4,77 vs 4,99cm; p=0,0003. Houve mais sobreviventes entre os portadores de cardiomiopatia idiopática e hipertensiva do que entre os chagásicos e doença coronariana. Na análise multivariada permaneceram como variáveis preditoras independentes da mortalidade o DDVE > 7,8 cm (HR 1,95, o Na 14 seg (HR 1,69. CONCLUSÃO: O estudo permite predizer quais os pacientes com insuficiência cardíaca que poderão apresentar uma boa sobrevida após a alta e os com maior possibilidade de longa sobrevivência após a alta.OBJECTIVE: To study the major clinical characteristics of patients with heart failure who survived more than 24 months after hospitalization for compensation. METHODS: The study comprised 126 patients with heart failure in functional class III or IV, with a mean age of 51.7 years. Most patients were men (73%, had a mean ejection fraction (EF of 0.36 and left ventricular diastolic

  16. Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer



    Objective To explore the association between different epidermal growth factor receptor(EGFR)mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer(NSCLC).Methods A retrospective cohort study was performed to assess146 patients with advanced NSCLC at Cancer

  17. A Case of Epidermal Nervous Syndrome with a Novel Association of Congenital Cystic Dysplastic Kidney with Numerous Nephroblastic Proliferations


    Epidermal nevus syndrome is a broad term encompassing several disease processes. These entities are united by their association with epidermal nevi...and extracutaneous abnormalities. Renal aberrancies associated with this syndrome include nephroblastoma, hamartomas, hypoplasia, and renal agenesis...However, there are no well-described, documented cases of dysplastic kidney with cystic nephroblastic proliferation associated with epidermal nevus

  18. Expression of epidermal growth factor receptors in human endometrial carcinoma

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B


    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent....../inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas....

  19. Isolation, characterization and comparison of mammalian epidermal prekeratins.

    Bladon, P T; Taylor, M; Wood, E J; Cunliffe, W J


    1. The lower living layers of mammalian epidermis contain a cytoplasmic tonofilament protein, prekeratin, believed to be the precursor of the keratin which is found in the outer dead cell layer or stratum corneum. 2. Prekeratin is distinguished by its property of being extractable from epidermis homogenized in the presence of citric acid trisodium citrate buffer pH 2.65. 3. In the present study we have compared the epidermal prekeratins from ten mammalian species and have shown them to be of similar amino acid composition. 4. Conditions have been established for studying the immunology of these insoluble proteins and examination of their immunological properties has shown that they are similar to one another but that their antigenic determinants are different from those of callus keratin. 5. The SDS polyacrylamide gel electrophoretic patterns of these proteins differ widely and we have also demonstrated anatomical site variation by this method.

  20. Epidermal segmentation in high-definition optical coherence tomography.

    Li, Annan; Cheng, Jun; Yow, Ai Ping; Wall, Carolin; Wong, Damon Wing Kee; Tey, Hong Liang; Liu, Jiang


    Epidermis segmentation is a crucial step in many dermatological applications. Recently, high-definition optical coherence tomography (HD-OCT) has been developed and applied to imaging subsurface skin tissues. In this paper, a novel epidermis segmentation method using HD-OCT is proposed in which the epidermis is segmented by 3 steps: the weighted least square-based pre-processing, the graph-based skin surface detection and the local integral projection-based dermal-epidermal junction detection respectively. Using a dataset of five 3D volumes, we found that this method correlates well with the conventional method of manually marking out the epidermis. This method can therefore serve to effectively and rapidly delineate the epidermis for study and clinical management of skin diseases.

  1. Transcriptional responses of human epidermal keratinocytes to Oncostatin-M.

    Finelt, Nika; Gazel, Alix; Gorelick, Steven; Blumenberg, Miroslav


    Oncostatin-M (OsM) plays an important role in inflammatory and oncogenic processes in skin, including psoriasis and Kaposi sarcoma. However, the molecular responses to OsM in keratinocytes have not been explored in depth. Here we show the results of transcriptional profiling in OsM-treated primary human epidermal keratinocytes, using high-density DNA microarrays. We find that OsM strongly and specifically affects the expression of many genes, in particular those involved with innate immunity, angiogenesis, adhesion, motility, tissue remodeling, cell cycle and transcription. The timing of the responses to OsM comprises two waves, early at 1h, and late at 48 h, with much fewer genes regulated in the intervening time points. Secreted cytokines and growth factors and their receptors, as well as nuclear transcription factors, are primary targets of OsM regulation, and these, in turn, effect the secondary changes.

  2. Epidermal growth factor pathway substrate 15, Eps15

    Salcini, A E; Chen, H; Iannolo, G


    Eps15 was originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR). Eps15 has a tripartite structure comprising a NH2-terminal portion, which contains three EH domains, a central putative coiled-coil region, and a COOH-terminal domain containing...... of EGF and transferrin, demonstrating that both proteins are components of the endocytic machinery. Since the family of EH-containing proteins is implicated in various aspects of intracellular sorting, biomolecular strategies aimed at interfering with these processes can now be envisioned....... These strategies have potentially far reaching implications extending to the control of cell proliferation. In this regard, it is of note that Eps15 has the potential of transforming NIH-3T3 cells and that the eps15 gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias, thus implicating...

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

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


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

  4. Aceclofenac induced Stevens-Johnson/toxic epidermal necrolysis overlap syndrome

    Kaderthambi Hajamohideen Nooru Ameen


    Full Text Available The purpose of this paper is to report a rare occurrence of Stevens-Johnson/Toxic epidermal necrolysis (SJS/TEN overlap syndrome after the use of aceclofenac. A 38 year old healthy adult male presented with rapidly evolving rash over face and upper body with ulceration of buccal mucosa and breathlessness after taking aceclofenac tablet. Naranjo score for this adverse drug event was six, thereby making it a probable adverse drug reaction. Despite aggressive fluid resuscitation and use of antihistamines and systemic steroids, patient′s health rapidly worsened and died within six hours of presentation. Aceclofenac induced SJS/TEN overlap is an extremely rare clinical association previously reported only once in medical literature. To the best of our knowledge, this is the first case report of such an association in the Indian population. We are presenting this case to highlight the serious adverse reactions possible from a routinely prescribed drug.

  5. Cell and molecular biology of epidermal growth factor receptor.

    Ceresa, Brian P; Peterson, Joanne L


    The epidermal growth factor receptor (EGFR) has been one of the most intensely studied cell surface receptors due to its well-established roles in developmental biology, tissue homeostasis, and cancer biology. The EGFR has been critical for creating paradigms for numerous aspects of cell biology, such as ligand binding, signal transduction, and membrane trafficking. Despite this history of discovery, there is a continual stream of evidence that only the surface has been scratched. New ways of receptor regulation continue to be identified, each of which is a potential molecular target for manipulating EGFR signaling and the resultant changes in cell and tissue biology. This chapter is an update on EGFR-mediated signaling, and describes some recent developments in the regulation of receptor biology.




    Full Text Available A morphological study of 38 species of Baccharis used in traditional medicinewas carried out to provide some epidermal characters that will contribute to theknowledge of the genus. The present study revealed: 1 seven different types oftrichomes: conical, aseptate fl agellate, fi liform fl agellate, 1-armed, 2-4-armed,bulbiferous fl agellate, and glandular biseriate; 2 that 28 of the total of 38 specieshave trichomes in tufts; 3 six different types of stomata: anomocytic, anisocytic,cyclocytic, actinocytic, tetracytic, and staurocytic; 4 that some trichome types,such as 2-4-armed (B. dracunculifolia and aseptate fl agellate branched (B. trinervis,show a high diagnostic value; 5 that the stomata types can be used to differentiatespecies with similar trichomes type (e.g. B. trimera and B. articulata.Illustrations of the studied characters are provided.

  7. A case report on toxic epidermal necrolysis with etoricoxib

    J S Kameshwari


    Full Text Available Etoricoxib is a selective cyclo-oxygenase 2 (COX-2 enzyme inhibitor and is exploited for its analgesic activity in various disease conditions like osteoarthritis, gouty arthritis, acute pain including postoperative dental pain and primary dysmenorrhea, etc. Although highly efficacious in pain management the safety profile of this COX-2 inhibitor is yet to be established in a broader sense. Short-term clinical trials and postmarketing surveillance have shown a very rare incidence of very serious skin reactions like Steven Johnson syndrome or toxic epidermal necrolysis (TEN. In this case report, we summarize regarding a patient who developed TEN after treatment with etoricoxib for osteoarthritis that later resolved in 15 days after withdrawal and symptomatic treatment.

  8. Perforated Sigmoid Diverticulitis in the Presence of Toxic Epidermal Necrolysis

    P. Heye


    Full Text Available Even though the incidence of toxic epidermal necrolysis (TEN is low, it is also associated with a high mortality rate. The condition predominantly affects the skin, but may also affect the gastrointestinal tract, dramatically increasing mortality. We present a case of perforated sigmoid diverticulitis in the presence of TEN. The patient was taking medication, known to be a risk factor, and presented an affected total body surface area and temporal development similar to previously reported cases of TEN. Characteristic abdominal symptoms, however, were missing. Gastrointestinal involvement in TEN appears to be a poor prognostic factor; medical staff must therefore be alert to patients with TEN who complain of abdominal discomfort. The exact pathogenesis, however, remains unclear.

  9. Interferon gamma-dependent transactivation of epidermal growth factor receptor.

    Burova, Elena; Vassilenko, Konstantin; Dorosh, Victoria; Gonchar, Ilya; Nikolsky, Nikolai


    The present report provides evidence that, in A431 cells, interferon gamma (IFNgamma) induces the rapid (within 5 min), and reversible, tyrosine phosphorylation of the epidermal growth factor receptor (EGFR). IFNgamma-induced EGFR transactivation requires EGFR kinase activity, as well as activity of the Src-family tyrosine kinases and JAK2. Here, we show that IFNgamma-induced STAT1 activation in A431 and HeLa cells partially depends on the kinase activity of both EGFR and Src. Furthermore, in these cells, EGFR kinase activity is essential for IFNgamma-induced ERK1,2 activation. This study is the first to demonstrate that EGFR is implicated in IFNgamma-dependent signaling pathways.

  10. Epidermal growth factor in rat milk is dependent on insulin

    Thulesen, J; Poulsen, Steen Seier; Nexo, E;


    decreased when compared to the control group. In contrast, the total protein concentration in milk from the untreated diabetic rats was similar to the concentration in milk from the control rats. Insulin-treatment of diabetic rats almost completely reversed the decrease in the milk volume......Epidermal growth factor (EGF) was measured in milk from four groups of rats: untreated diabetic, insulin-treated diabetic, insulin-treated normal and control rats. In the untreated diabetic group the volume of milk, and the concentration of EGF and the total output of EGF were significantly...... of EGF from the mammary glands is dependent on insulin and that the decrement in milk-EGF from diabetic rats is selective when compared to the content of protein in milk....

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

    David E. Heppner


    Full Text Available 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.

  12. Toxic epidermal necrolysis associated with deflazacort therapy with nephrotic syndrome

    Eun Chae Lee


    Full Text Available Toxic epidermal necrolysis (TEN is a drug-related fatal disease. Extensive necrosis of the epidermis can lead to serious complications. This report describes two cases of TEN, associated with deflazacort (DFZ, in two boys, aged 4 years and 14 years, with nephrotic syndrome (NS. The 14-year-old male teenager received DFZ following NS relapse. After 17 days, pruritic papules appeared on the lower extremities. Another case involved a 4-year-old boy receiving DFZ and enalapril. After a 41-day DFZ treatment period, erythematous papules appeared on the palms and soles. Within 3 days, both boys developed widespread skin lesions (>50% and were admitted to the intensive care unit for resuscitative and supportive treatment. The patients showed improvement after intravenous immunoglobulin-G therapy. Owing to the rapid, fatal course of TEN, clinicians need to be aware of the adverse effects of this drug when treating cases of NS.

  13. Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes

    Choudhary, Vivek; Olala, Lawrence O.; Kaddour-Djebbar, Ismail; Helwa, Inas; Bollag, Wendy B.


    Background Protein kinase D (PKD or PKD1) is a serine/threonine protein kinase that has been shown to play a role in a variety of cellular processes; however, the function of PKD1 in the skin has not been fully investigated. The balance between proliferation and differentiation processes in the predominant cells of the epidermis, the keratinocytes, is essential for normal skin function. Objective To investigate the effect of PKD1 deficiency on proliferation and differentiation of epidermal keratinocytes. Methods We utilized a floxed PKD1 mouse model such that infecting epidermal keratinocytes derived from these mice with an adenovirus expressing Cre-recombinase allowed us to determine the effect of PKD1 gene loss in vitro. Proliferation and differentiation were monitored using qRT-PCR, Western blot, transglutaminase activity assays, [3H]thymidine incorporation into DNA and cell cycle analysis. Results A significant decrease in PKD1 mRNA and protein levels was achieved in adenoviral Cre-recombinase-infected cells. Deficiency of PKD1 resulted in significant increases in the mRNA and protein expression of various differentiation markers such as loricrin, involucrin, and keratin 10 either basally and/or upon stimulation of differentiation. PKD1-deficient keratinocytes also showed an increase in transglutaminase expression and activity, indicating an anti-differentiative role of PKD1. Furthermore, the PKD1-deficient keratinocytes exhibited decreased proliferation. However, PKD1 loss had no effect on stem cell marker expression. Conclusions Cre-recombinase-mediated knockdown represents an additional approach demonstrating that PKD1 is an anti-differentiative, pro-proliferative signal in mouse keratinocytes. PMID:25450094

  14. Toxic epidermal necrolysis, DRESS, AGEP: Do overlap cases exist?

    Bouvresse Sophie


    Full Text Available Abstract Background Severe cutaneous adverse reactions to drugs (SCARs include acute generalized exanthematous pustulosis (AGEP, drug reaction with eosinophilia and systemic symptoms (DRESS and epidermal necrolysis (Stevens-Johnson syndrome–toxic epidermal necrolysis [SJS-TEN]. Because of the varied initial presentation of such adverse drug reactions, diagnosis may be difficult and suggests overlap among SCARs. Overlapping SCARs are defined as cases fulfilling the criteria for definite or probable diagnosis of at least 2 ADRs according to scoring systems for AGEP, DRESS and SJS-TEN. We aimed to evaluate the prevalence of overlap among SCARs among cases in the referral hospital in France. Methods We retrospectively analyzed data for 216 patients hospitalized in the referral centre over 7 years with a discharge diagnosis of AGEP (n = 45, DRESS (n = 47, SJS-TEN (n = 80 or “drug rash” (n = 44. Each case with detailed clinical data and a skin biopsy specimen was scored for AGEP, DRESS and SJS-TEN by use of diagnostic scores elaborated by the RegiSCAR group. Results In total, 45 of 216 cases (21% had at least 2 possible diagnoses: 35 had a single predominant diagnosis (definite or probable, 7 had several possible diagnoses and 3 (2.1% of 145 confirmed SCARs were overlap SCARs. Conclusions Despite ambiguities among SCARs, confirmed overlap cases are rare. This study did not avoid pitfalls linked to its retrospective nature and selection bias. In the acute stage of disease, early identification of severe ADRs can be difficult because of clinical or biologic overlapping features and missing data on histology, biology and evolution. Retrospectively analyzing cases by use of diagnostic algorithms can lead to reliable discrimination among AGEP, DRESS and SJS-TEN.

  15. Expression of T-Lymphocyte Markers in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

    Lee, Changro; Kim, Joo Heung; Lim, Sung Mook; Park, Hyung Seok; Kim, Seung Il; Park, Byeong-Woo


    Purpose The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. Methods Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels. Immunohistochemistry analysis was performed using paired primary and metastatic tissues of 29 HER2-positive tumors treated with systemic chemotherapy and HER2-directed therapy. Results HER2 mRNA was mutually exclusive of T-lymphocyte markers, and a significant correlation between T-cell markers was observed in the cBioPortal for Cancer Genomics. According to analysis of the Kaplan-Meier plotter, the impact of T-lymphocyte marker expression on survival was statistically insignificant in clinical HER2-positive tumors, irrespective of the cutoff levels. However, in the intrinsic HER2-positive subtype, the individual analyses of T-cell markers except for FOXP3 and combined analysis showed significantly favorable survival irrespective of cutoff points. Although the small clinical sample size made it difficult to show the statistical relevance of immunohistochemistry findings, good responses to neoadjuvant treatments might be associated with positive expression of combined T-lymphocyte markers, and approximately half of the samples showed discordance of combined markers between baseline and resistant tumors. Conclusion T-lymphocyte markers could be favorable prognostic factors in HER2-positive breast cancers; however, a consensus on patient section criteria, detection methods, and cutoff value could not be reached. The resistance to HER2-directed therapy might

  16. Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer

    Meng, Xiangjiao; Huang, Zhaoqin; Di, Jian; Mu, Dianbin; Wang, Yawei; Zhao, Xianguang; Zhao, Hanxi; Zhu, Wanqi; Li, Xiaolin; Kong, Lingling; Xing, Ligang


    Abstract The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for

  17. p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells

    Mardaryev, Andrei N.; Gdula, Michal R.; Yarker, Joanne L.; Emelianov, Vladimir N.; Poterlowicz, Krzysztof; Sharov, Andrey A.; Sharova, Tatyana Y.; Scarpa, Julie A.; Chambon, Pierre; Botchkarev, Vladimir A.; Fessing, Michael Y.


    Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression. The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood. Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis. During epidermal development, the locus relocates away from the nuclear periphery towards the nuclear interior into a compartment enriched in SC35-positive nuclear speckles. Relocation of the EDC locus occurs prior to the full activation of EDC genes involved in controlling terminal keratinocyte differentiation and is a lineage-specific, developmentally regulated event controlled by transcription factor p63, a master regulator of epidermal development. We also show that, in epidermal progenitor cells, p63 directly regulates the expression of the ATP-dependent chromatin remodeller Brg1, which binds to distinct domains within the EDC and is required for relocation of the EDC towards the nuclear interior. Furthermore, Brg1 also regulates gene expression within the EDC locus during epidermal morphogenesis. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development. PMID:24346698

  18. Improved epidermal barrier formation in human skin models by chitosan modulated dermal matrices

    Mieremet, Arnout; Rietveld, Marion; Absalah, Samira; van Smeden, Jeroen


    Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan. Herein, we report that these collagen-chitosan FTMs (CC-FTMs) possess a well-organized epidermis and maintain both the early and late differentiation programs as in FTMs. Distinctively, the epidermal cell activation is reduced in CC-FTMs to levels observed in NHS. Dermal-epidermal interactions are functional in both FTM types, based on the formation of the basement membrane. Evaluation of the barrier structure by the organization of the extracellular lipid matrix of the stratum corneum revealed an elongated repeat distance of the long periodicity phase. The ceramide composition exhibited a higher resemblance of the NHS, based on the carbon chain-length distribution and subclass profile. The inside-out barrier functionality indicated by the transepidermal water loss is significantly improved in the CC-FTMs. The expression of epidermal barrier lipid processing enzymes is marginally affected, although more restricted to a single granular layer. The novel CC-FTM resembles the NHS more closely, which makes them a promising tool for epidermal barrier related studies. PMID:28333992

  19. Dynamic tracing for epidermal growth factor receptor mutations in urinary circulating DNA in gastric cancer patients.

    Shi, Xiu-Qin; Xue, Wen-Hua; Zhao, Song-Feng; Zhang, Xiao-Jian; Sun, Wukong


    The mutations of epidermal growth factor receptor are detected in gastric cancer, indicating its suitability as a target for receptor tyrosine kinase inhibitors, as well as a marker for clinical outcome of chemotherapeutic treatments. However, extraction of quality tumor tissue for molecular processes remains challenging. Here, we aimed to examine the clinical relevance of urinary cell-free DNA as an alternative tumor material source used specifically for monitoring epidermal growth factor receptor mutations. Therefore, 120 gastric cancer patients with epidermal growth factor receptor mutations and 100 healthy controls were recruited for the study. The gastric patients also received epidermal growth factor receptor inhibitor treatment for a serial monitoring study. Paired primary tumor specimens were obtained with blood and urine samples, which were taken at a 1-month interval for a duration of 12 months. We found that urinary cell-free DNA yielded a close agreement of 92% on epidermal growth factor receptor mutation status when compared to primary tissue at baseline, and of 99% epidermal growth factor receptor mutation status when compared to plasma samples at different time points. Thus, our data suggest that urinary cell-free DNA may be a reliable source for screening and monitoring epidermal growth factor receptor mutations in the primary gastric cancer.

  20. Proliferative response of fibroblasts expressing internalization-deficient epidermal growth factor (EGF) receptors is altered via differential EGF depletion effect.

    Reddy, C C; Wells, A; Lauffenburger, D A


    We describe experiments comparing the proliferation responses to epidermal growth factor (EGF) by NR6 fibroblasts expressing genetically engineered epidermal growth factor receptors (EGFRs). These cells present either wild-type (WT) EGFR or a cytoplasmic domain-truncated (c'973) EGFR that exhibits a decreased ligand-induced internalization rate constant. In two distinct in vitro proliferation assays, with or without medium replenishment, we measured the specific cell proliferation rate constants and EGF depletion kinetics for both WT and c'973 cells. When EGF depletion is minimized by replenishment, the EGF concentration dependencies of the two cell types are similar, whereas when EGF depletion is not prevented, maximal proliferation of WT cells requires an initial EGF concentration that is approximately 10x that required by c'973 cells. However, when EGF depletion is accounted for, the dependencies of growth rate for the two cell types on the current EGF concentration in both assays are essentially identical. Our results demonstrate that diminished depletion of EGF from the extracellular medium is a major reason for increased mitogenic sensitivity to EGF by cells possessing internalization-deficient receptors.

  1. Sequence, evolution and tissue expression patterns of an epidermal type I keratin from the shark Scyliorhinus stellaris.

    Schaffeld, Michael; Höffling, Simon; Jürgen, Markl


    From the shark Scyliorhinus stellaris we cloned and sequenced a cDNA encoding a novel type I keratin, termed SstK10. By MALDI-MS peptide mass fingerprinting of cytoskeletal proteins separated on polyacrylamide gels, we assigned SstK10 to a 46-kDa protein which is the major epidermal type I ("IE") keratin in this fish and is specifically expressed in stratified epithelia. In a phylogenetic tree based on type I keratin sequences and with lamprey keratins applied as outgroup, SstK10 branches off in a rather basal position. This tree strongly supports the concept that teleost keratins and tetrapod keratins resulted from two independent gene radiation processes. The only exception is human K18 because its orthologs have been found in all jawed vertebrates (Gnathostomata) studied; in the tree, they form a common, most early branch, with the shark version, SstK18, in the most basal position. Thus, the sequences of SstK10 and SstK18 also favor the classical view of vertebrate evolution that considers the cartilaginous fishes as the most ancient living Gnathostomata. To determine the overall expression patterns of epidermal ("E") and simple epithelial ("S") keratins in this shark, we furthermore tested a panel of monoclonal anti-keratin antibodies by immunofluorescence microscopy of frozen tissue sections, and in immunoblots of cytoskeletal preparations, demonstrating that immunodetection of specific keratins is a convenient method to characterize epithelial tissues in shark.

  2. Clinical Experience with First-generation Epidermal Growth Factor Receptor 
Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients 
with Brain Metastasis

    Huixing DONG


    Full Text Available Background and objective A survival analysis and the influencing factors for non-small cell lung cancer (NSCLC patients with brain metastases accepting first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs treatment have not yet been elucidated to date. In this study, we collected and analyzed the survival data of NSCLC patients with brain metastasis to obtain evidence and to provide guidance in clinical practice. Methods NSCLC patients with brain metastases who were treated with first-generation EGFR-TKIs were retrospectively collected in 2012-2013 from Shanghai Chest Hospital, Shanghai Jiao Tong University. The Kaplan-Meier method and Cox regression were performed for univariate and multivariate analyses, respectively, to explore the independent predictors influencing the survival of patients with NSCLC brain metastases. Results The median progression-free survival (PFS and median overall survival (OS of all patients treated with first-generation EGFR-TKIs were 10.0 months (95%CI: 8.3-11.7 and 28.0 months (95%CI: 22.9-33.1, respectively. Pathological subtypes were the independent predictors of PFS (P=0.001, and tumor differentiations were the independent predictors of OS (P=0.050. Conclusion First-generation EGFR-TKIs showed promising efficacy in NSCLC patients with brain metastases. PFS was longer in patients with adenocarcinoma than in those with a non-adenocarcinoma subtype. OS was longer in patients with differentiated tumors than in those who developed poorly differentiated tumors.

  3. Epidermization in the esophageal mucosa: unusual epithelial changes clearly detected by Lugol's staining.

    Nakanishi, Y; Ochiai, A; Shimoda, T; Yamaguchi, H; Tachimori, Y; Kato, H; Watanabe, H; Hirohashi, S


    A 58-year-old Japanese man with superficial esophageal cancer accompanied by unusual epithelial changes, including esophageal mucosal epidermization, is reported. Staining with Lugol's iodine clearly showed irregular unstained lesions, which could not be seen clearly macroscopically, in the resected specimen. Histologic examination of the irregular unstained areas showed definite granular and horny layers regarded as epidermization, acanthosis with slight nuclear enlargement, and epithelial atrophy. The immunohistochemical staining patterns of keratins in the epidermized and atrophic lesions were similar to those in the epidermis, and the keratin staining patterns of the acanthotic lesion were similar to those of the oral epithelium.

  4. Vulvar epidermal inclusion cyst as a long-term complication of female genital mutilation

    Ana Mercedes Victoria-Martínez


    Full Text Available We present a case report of a patient with epidermal inclusion cyst as a late complication of female genital mutilation (FGM. We describe the management of the patient, and a review of the literature. We report the clinical and pathological findings in a 37-year-old female patient from Nigeria, with a clitoral mass of 1 year duration. She declared to have an FGM since she was 5 years. The lesion was excised successfully with good cosmetic results. Histological examination revealed epidermal cyst with the presence of granular layer. An epidermal inclusion cyst can develop as a long-term consequence of FGM.

  5. Vulvar Epidermal Inclusion Cyst as a Long-term Complication of Female Genital Mutilation.

    Victoria-Martínez, Ana Mercedes; Cubells-Sánchez, Laura; Martínez-Leborans, Lorena; Sánchez-Carazo, José Luis; de Miquel, Víctor Alegre


    We present a case report of a patient with epidermal inclusion cyst as a late complication of female genital mutilation (FGM). We describe the management of the patient, and a review of the literature. We report the clinical and pathological findings in a 37-year-old female patient from Nigeria, with a clitoral mass of 1 year duration. She declared to have an FGM since she was 5 years. The lesion was excised successfully with good cosmetic results. Histological examination revealed epidermal cyst with the presence of granular layer. An epidermal inclusion cyst can develop as a long-term consequence of FGM.

  6. Basal cell carcinoma arising on a verrucous epidermal nevus: a case report.

    Viana, Analia; Aguinaga, Felipe; Marinho, Flauberto; Rodrigues, Rosangela; Cuzzi, Tullia; Ramos-E-Silva, Marcia


    We report a case of basal cell carcinoma that appeared from an epidermal verrucous nevus in a 61-year-old patient. The onset of basal cell carcinoma in sebaceous nevi, basal cell nevi and dysplastic nevi is relatively common, but it is rarely associated with epidermal verrucous nevi. There is no consensus on whether the two lesions have a common cellular origin or whether they merely represent a collision of two distinct tumors. Since this association - as with other malignant tumors - is rare, there is no need for prophylactic removal of epidermal verrucous nevi.

  7. Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab

    Zeuli Massimo


    Full Text Available Abstract Background Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR Gene Copy Number (GCN. Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC patients receiving chemotherapy plus Cetuximab. Methods One hundred and one advanced CRC patients (43 untreated- and 58 pre-treated were retrospectively studied by fluorescence in situ hybridization (FISH to assess EGFR-GCN and by immunohistochemistry (IHC to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR, progression-free survival (PFS and overall survival (OS. Results Increased EGFR-GCN was found in 60/101 (59% tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43. Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43 while it was 18% (10/56 in the group with previous lines of therapy (p Conclusion In metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.

  8. EphrinA5 suppresses colon cancer development by negatively regulating epidermal growth factor receptor stability.

    Wang, Tong-Hong; Chang, Junn-Liang; Ho, Jar-Yi; Wu, Hsiao-Chun; Chen, Tse-Ching


    Colon cancer is one of the most common human cancers worldwide. Owing to its aggressiveness and lethality, it is necessary to determine the mechanisms regulating the carcinogenesis of colon cancer. EphrinA5 has been reported to act as a putative tumor suppressor in glioma; however, little is known concerning the role of this protein in the context of colon cancer. To elucidate the biological significance of ephrinA5 in colon cancer, we examined ephrinA5 and epidermal growth factor receptor (EGFR) expression profiles in both colon cancer and normal tissues, using immunohistochemistry on a 96-spot tissue microarray. Gain-of-function and loss-of-function experiments were performed on the human colon cancer cell lines SW480 and WiDr to determine the biological effects of ephrinA5 in relation to cell proliferation, survival, and migration. It was found that ephrinA5 mRNA and protein levels were significantly reduced in colon cancer as compared with normal colon tissue specimens. EphrinA5 expression was also negatively associated with tumor differentiation and clinical stage. In colon cancer cell line models, ephrinA5 exerted an inhibitory effect on EGFR by promoting c-Cbl-mediated EGFR ubiquitination and degradation. EphrinA5 did not affect the transcriptional regulation of EGFR mRNA expression in colon cancer cells. Expression of ephrinA5 suppressed colon cancer cell proliferation, migration, and chemotherapeutic resistance. In conclusion, ephrinA5 inhibited colon cancer progression by promoting c-Cbl-mediated EGFR degradation. Our findings identify a novel mechanism that could be utilized to improve the therapeutic efficiency of EGFR-targeting strategies.

  9. Effects of epidermal growth factor receptor kinase inhibition on radiation response in canine osteosarcoma cells.

    Mantovani, Fernanda B; Morrison, Jodi A; Mutsaers, Anthony J


    Radiation therapy is a palliative treatment modality for canine osteosarcoma, with transient improvement in analgesia observed in many cases. However there is room for improvement in outcome for these patients. It is possible that the addition of sensitizing agents may increase tumor response to radiation therapy and prolong quality of life. Epidermal growth factor receptor (EGFR) expression has been documented in canine osteosarcoma and higher EGFR levels have been correlated to a worse prognosis. However, effects of EGFR inhibition on radiation responsiveness in canine osteosarcoma have not been previously characterized. This study examined the effects of the small molecule EGFR inhibitor erlotinib on canine osteosarcoma radiation responses, target and downstream protein expression in vitro. Additionally, to assess the potential impact of treatment on tumor angiogenesis, vascular endothelial growth factor (VEGF) levels in conditioned media were measured. Erlotinib as a single agent reduced clonogenic survival in two canine osteosarcoma cell lines and enhanced the impact of radiation in one out of three cell lines investigated. In cell viability assays, erlotinib enhanced radiation effects and demonstrated single agent effects. Erlotinib did not alter total levels of EGFR, nor inhibit downstream protein kinase B (PKB/Akt) activation. On the contrary, erlotinib treatment increased phosphorylated Akt in these osteosarcoma cell lines. VEGF levels in conditioned media increased after erlotinib treatment as a single agent and in combination with radiation in two out of three cell lines investigated. However, VEGF levels decreased with erlotinib treatment in the third cell line. Erlotinib treatment promoted modest enhancement of radiation effects in canine osteosarcoma cells, and possessed activity as a single agent in some cell lines, indicating a potential role for EGFR inhibition in the treatment of a subset of osteosarcoma patients. The relative radioresistance of

  10. Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation

    Faria, Jerusa A.Q.A.; Andrade, Carolina de; Goes, Alfredo M. [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Rodrigues, Michele A. [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Department of General Pathology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Gomes, Dawidson A., E-mail: [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil)


    The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells. - Highlights: • EGF, HB-EGF, TGF-α, β-Cellulin are involved in the EGFR nuclear translocation. • Amphiregulin and epiregulin did not promote nuclear translocation of EGFR. • EGF, HB-EGF, TGF-α and β-Cellulin have a role in SkHep-1 cells migration. • EGFR ligands associated with better prognosis don't stimulate EGFR translocation.

  11. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H. [Ohio State Univ., Columbus, OH (United States); Carlsson, J. [Uppsala Univ. (Sweden). Dept. of Radiation Sciences


    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of {sup 10}B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10{sup 5} {minus}10{sup 6} EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10{sup 8} boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight ({approximately} 6 kD), this has allowed us to construct relatively small bioconjugates containing {approximately} 900 boron atoms per EGF molecule{sup 3}, which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using {sup 131}I{minus} or {sup 99m}{Tc}-labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma.

  12. Epidermal development, growth control, and homeostasis in the face of centrosome amplification.

    Kulukian, Anita; Holland, Andrew J; Vitre, Benjamin; Naik, Shruti; Cleveland, Don W; Fuchs, Elaine


    As nucleators of the mitotic spindle and primary cilium, centrosomes play crucial roles in equal segregation of DNA content to daughter cells, coordination of growth and differentiation, and transduction of homeostatic cues. Whereas the majority of mammalian cells carry no more than two centrosomes per cell, exceptions to this rule apply in certain specialized tissues and in select disease states, including cancer. Centrosome amplification, or the condition of having more than two centrosomes per cell, has been suggested to contribute to instability of chromosomes, imbalance in asymmetric divisions, and reorganization of tissue architecture; however, the degree to which these conditions are a direct cause of or simply a consequence of human disease is poorly understood. Here we addressed this issue by generating a mouse model inducing centrosome amplification in a naturally proliferative epithelial tissue by elevating Polo-like kinase 4 (Plk4) expression in the skin epidermis. By altering centrosome numbers, we observed multiciliated cells, spindle orientation errors, and chromosome segregation defects within developing epidermis. None of these defects was sufficient to impart a proliferative advantage within the tissue, however. Rather, impaired mitoses led to p53-mediated cell death and contributed to defective growth and stratification. Despite these abnormalities, mice remained viable and healthy, although epidermal cells with centrosome amplification were still appreciable. Moreover, these abnormalities were insufficient to disrupt homeostasis and initiate or enhance tumorigenesis, underscoring the powerful surveillance mechanisms in the skin.

  13. In Vivo Cosmetic Product Efficacy Testing by Analyzing Epidermal Proteins Extracted from Tape Strips

    Marie Westman


    Full Text Available The objective of this in vivo pilot study was to investigate whether differential biomarker analysis from skin tape strips could be used, not only to evaluate the difference between treated and untreated skin, but also to evaluate the effect of different product treatments. Ten volunteers were included in the study, applying two different basic formulations on their forearms. After four weeks of product application, and also after one week of treatment remission, tape strips were collected from the different treatment sites, as well as from untreated skin. The biomarkers investigated were selected to cover different aspects of epidermal differentiation and in connection with moisturization and barrier function. Levels of Involucrin were increased in both treatments, compared to untreated skin, whereas the levels of Keratin-6 were decreased for both treatments. In addition, a pattern for increased levels of Hornerin and Claudin-1 was also detected. There were no significant differences between the two treatments, only for treatment compared to untreated, but there were tendencies for different effect on some of the biomarkers investigated, differences that may reach significance with increased sample size. The major differences between the two treatments in this study were seen after one week of product remission, although due to too small sample size these differences were not significant.


    Tomoko Oishi


    Full Text Available Introduction: Staphylococcal scaled skin syndrome (SSSS presents generalized form bullous impetigo caused by Staphylococcus aureus (S. aureus infection, typically seen in infants and children. SSSS may occur also in adults; however, the majority of adult cases are those with immunosuppression. Atypical clinical features of impetigo in adults sometimes make it difficult to diagnose correctly. Case Report: A 74-year-old healthy woman was hospitalized, complaining of extensive desquamative erythema and a number of erosions. She was administered oral antiviral drugs under suspicion of herpes zoster prior to 10 days. Initial diagnosis on the admission was toxic epidermal necrolysis (TEN due to antiviral tablets; however, steroid pulse therapy resulted in no effect. Bacterial culture yielded coagulase-positive methicillin-resistent S. aureus, producing exfoliative toxin B. A biopsy specimen showed subcorneal splitting of the epidermis. The diffuse erosions gradually improved over 10 days by the treatment with intravenous antibiotics. Conclusions: The differentiation between streptococcal scaled skin syndrome (SSSS and TEN is sometimes difficult. It is important to remind SSSS when we suspect TEN, even in healthy adults..

  15. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain.

    Jeffrey C Lee


    Full Text Available BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132 of glioblastomas and 12.5% (1/8 of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

  16. Wartime major venous vessel injuries.

    Hudorovic, Narcis


    The aim of this study is to declare our experience and to identify the important factors that influence the mortality and morbidity in patients with combat-related penetrating wounds of the abdomen (CR-PWA) with major venous vessel injuries. Twenty-six wounded with combat-related injuries of major abdominal venous vessels, admitted in the University Clinic cardiovascular surgery department during the period from 1 August 1991 through 30 October 1995, were analyzed. Patients with concomitant injured arteries and extra-abdominal injuries (n=150; 85.2%) were excluded from this study. The Penetrating Abdominal Trauma Index (PATI) score for each patient was calculated. Fifteen patients (57.69%) sustained with PATI score greater than 25 died. The mean duration of hospitalization was 16 days (range 0-86). The average hospitalization time for those surviving their complications was 17 days with a PATI of 25 or less, and 43 days with a score more than 25. Three clinical assessments of the long-term outcome were performed after a median of about 3, 5 and 10 years, respectively. Surviving patients (42.31%) were symptom free and had normal Duplex scans as well as no other surgical related complications. Higher PATI scores, postoperative complications and reoperations exert an unfavorable effect on patient outcome.

  17. Collagen hydrogels strengthened by biodegradable meshes are a basis for dermo-epidermal skin grafts intended to reconstitute human skin in a one-step surgical intervention.

    Hartmann-Fritsch, Fabienne; Biedermann, Thomas; Braziulis, Erik; Luginbühl, Joachim; Pontiggia, Luca; Böttcher-Haberzeth, Sophie; van Kuppevelt, Toin H; Faraj, Kaeuis A; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst


    Extensive full-thickness skin loss, associated with deep burns or other traumata, represents a major clinical problem that is far from being solved. A promising approach to treat large skin defects is the use of tissue-engineered full-thickness skin analogues with nearly normal anatomy and function. In addition to excellent biological properties, such skin substitutes should exhibit optimal structural and mechanical features. This study aimed to test novel dermo-epidermal skin substitutes based on collagen type I hydrogels, physically strengthened by two types of polymeric net-like meshes. One mesh has already been used in clinical trials for treating inguinal hernia; the second one is new but consists of a FDA-approved polymer. Both meshes were integrated into collagen type I hydrogels and dermo-epidermal skin substitutes were generated. Skin substitutes were transplanted onto immuno-incompetent rats and analyzed after distinct time periods. The skin substitutes homogeneously developed into a well-stratified epidermis over the entire surface of the grafts. The epidermis deposited a continuous basement membrane and dermo-epidermal junction, displayed a well-defined basal cell layer, about 10 suprabasal strata and a stratum corneum. Additionally, the dermal component of the grafts was well vascularized. Copyright © 2012 John Wiley & Sons, Ltd.

  18. Optical characterization of epidermal cells and their relationship to DNA recovery from touch samples [version 1; referees: 2 approved

    Cristina E. Stanciu


    Full Text Available The goal of this study was to investigate the relative contributions of different cellular and genetic components to biological samples created by touch or contact with a surface – one of the most challenging forms of forensic evidence. Touch samples were generated by having individuals hold an object for five minutes and analyzed for quantity of intact epidermal cells, extracellular DNA, and DNA from pelleted cell material after elution from the collection swab. Comparisons were made between samples where individuals had washed their hands immediately prior to handling and those where hand washing was not controlled. The vast majority (84-100% of DNA detected in these touch samples was extracellular and was uncorrelated to the number of epidermal cells detected. Although little to no extracellular or cell pellet-associated DNA was detected when individuals washed their hands prior to substrate handling, we found that a significant number of epidermal cells (between ~5x103 and ~1x105 could still be recovered from these samples, suggesting that other types of biological information may be present even when no amplifiable nuclear DNA is present. These results help to elucidate the biological context for touch samples and characterize factors that may contribute to patterns of transfer and persistence of genetic material in forensic evidence.

  19. Effects of soap-water wash on human epidermal penetration.

    Zhu, Hanjiang; Jung, Eui-Chang; Phuong, Christina; Hui, Xiaoying; Maibach, Howard


    Skin decontamination is a primary interventional method used to decrease dermal absorption of hazardous contaminants, including chemical warfare agents, pesticides and industrial pollutants. Soap and water wash, the most common and readily available decontamination system, may enhance percutaneous absorption through the "wash-in effect." To understand better the effect of soap-water wash on percutaneous penetration, and provide insight to improving skin decontamination methods, in vitro human epidermal penetration rates of four C(14) -labeled model chemicals (hydroquinone, clonidine, benzoic acid and paraoxon) were assayed using flow-through diffusion cells. Stratum corneum (SC) absorption rates of these chemicals at various hydration levels (0-295% of the dry SC weights) were determined and compared with the results of the epidermal penetration study to clarify the effect of SC hydration on skin permeability. Results showed accelerated penetration curves of benzoic acid and paraoxon after surface wash at 30 min postdosing. Thirty minutes after washing (60 min postdosing), penetration rates of hydroquinone and benzoic acid decreased due to reduced amounts of chemical on the skin surface and in the SC. At the end of the experiment (90 min postdosing), a soap-water wash resulted in lower hydroquinone penetration, greater paraoxon penetration and similar levels of benzoic acid and clonidine penetration compared to penetration levels in the non-wash groups. The observed wash-in effect agrees with the enhancement effect of SC hydration on the SC chemical absorption rate. These results suggest SC hydration derived from surface wash to be one cause of the wash-in effect. Further, the occurrence of a wash-in effect is dependent on chemical identity and elapsed time between exposure and onset of decontamination. By reducing chemical residue quantity on skin surface and in the SC reservoir, the soap-water wash may decrease the total quantity of chemical absorbed in the

  20. Regulation of epidermal Langerhans cell migration by lactoferrin.

    Cumberbatch, M; Dearman, R J; Uribe-Luna, S; Headon, D R; Ward, P P; Conneely, O M; Kimber, I


    Lactoferrin (LF) is a member of the transferrin family of iron-binding glycoproteins to which several anti-inflammatory functions have been ascribed. LF has been shown to down-regulate expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha), although the possibility has been raised that the activity of LF in this regard was indirect and secondary to its ability to bind to and inactivate the bacterial lipopolysaccharide (LPS) used to induce cytokine production. However, the identification of putative membrane receptors for LF raises the possibility that the interaction of LF with its receptor may be one important route through which this protein exerts anti-inflammatory activity. In the present investigations the biological properties of LF have been examined in a model of cutaneous immune function where the allergen-induced migration of epidermal Langerhans cells (LC) from the skin and their subsequent accumulation as dendritic cells (DC) in skin-draining lymph nodes are known to be dependent upon the de novo synthesis of TNF-alpha, but independent of exogenous LPS. Consistent with the protein having direct anti-inflammatory properties, it was found that the intradermal injection of recombinant murine LF (either iron-saturated or iron-depleted LF) inhibited significantly allergen (oxazolone) -induced LC migration and DC accumulation. That these inhibitory effects were secondary to the inhibition of local TNF-alpha synthesis was suggested by the findings that first, LF was unable to inhibit LC migration induced by intradermal injection of TNF-alpha itself, and second, that migration stimulated by local administration of another epidermal cytokine, interleukin 1beta, which is also dependent upon TNF-alpha production, was impaired significantly by prior treatment with LF. Finally, immunohistochemical analyses demonstrated the presence of LF in skin, associated primarily with keratinocytes. Collectively these data support the possession by

  1. Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes

    Philpott Michael P


    Full Text Available Abstract Background The human cell cycle transcription factor FOXM1 is known to play a key role in regulating timely mitotic progression and accurate chromosomal segregation during cell division. Deregulation of FOXM1 has been linked to a majority of human cancers. We previously showed that FOXM1 was upregulated in basal cell carcinoma and recently reported that upregulation of FOXM1 precedes malignancy in a number of solid human cancer types including oral, oesophagus, lung, breast, kidney, bladder and uterus. This indicates that upregulation of FOXM1 may be an early molecular signal required for aberrant cell cycle and cancer initiation. Results The present study investigated the putative early mechanism of UVB and FOXM1 in skin cancer initiation. We have demonstrated that UVB dose-dependently increased FOXM1 protein levels through protein stabilisation and accumulation rather than de novo mRNA expression in human epidermal keratinocytes. FOXM1 upregulation in primary human keratinocytes triggered pro-apoptotic/DNA-damage checkpoint response genes such as p21, p38 MAPK, p53 and PARP, however, without causing significant cell cycle arrest or cell death. Using a high-resolution Affymetrix genome-wide single nucleotide polymorphism (SNP mapping technique, we provided the evidence that FOXM1 upregulation in epidermal keratinocytes is sufficient to induce genomic instability, in the form of loss of heterozygosity (LOH and copy number variations (CNV. FOXM1-induced genomic instability was significantly enhanced and accumulated with increasing cell passage and this instability was increased even further upon exposure to UVB resulting in whole chromosomal gain (7p21.3-7q36.3 and segmental LOH (6q25.1-6q25.3. Conclusion We hypothesise that prolonged and repeated UVB exposure selects for skin cells bearing stable FOXM1 protein causes aberrant cell cycle checkpoint thereby allowing ectopic cell cycle entry and subsequent genomic instability. The aberrant

  2. Nevo da epidermólise bolhosa: caso clínico e revisão da literatura Epidermolysis bullosa nevus: case report and literature review

    Carolina Porto Cotrim


    Full Text Available Lesões melanocíticas adquiridas assemelhando-se à melanoma têm sido descritas nos principais grupos da Epidermólise bolhosa, e referidas como "Nevos da Epidermólise bolhosa''. Induzem facilmente ao erro diagnóstico, apesar de nenhuma transformação maligna ter sido descrita. Relatamos o desenvolvimento de um nevo melanocítico adquirido grande no local de bolhas recorrentes em uma criança de 5 anos portadora de Epidermólise bolhosa simples. O padrão dermatoscópico global foi sugestivo de benignidade, e os achados histopatológicos foram compatíveis com um nevo melanocítico composto. Este é o primeiro caso de um Nevo da Epidermólise bolhosa publicado na literatura brasileiraAcquired melanocytic lesions resembling malignant melanoma have been described in all major categories of Epidermolysis bullosa and referred to as "Epidermolysis bullosa nevi''. They easily induce to diagnostic error, although no malignant transformation has been reported. We report the development of a large acquired melanocytic nevus at a site of recurrent blisters in a 5-year-old child with Epidermolysis bullosa simplex. The global dermoscopic pattern was suggestive of benignity, and the histopathological findings were compatible with a compound melanocytic nevus. This is the first published case of Epidermolysis bullosa nevi in Brazilian literature. Despite their benign behavior, we emphasize the importance of regular clinical and dermoscopic monitoring, since a malignant course still cannot be totally excluded

  3. Ceftriaxone-induced toxic epidermal necrolysis mimicking burn injury: a case report

    Billig Allan


    Full Text Available Abstract Introduction Toxic epidermal necrolysis is a rare exfoliative disorder with a high mortality rate. Case presentation We present a 70-year-old woman of Iranian descent who presented with toxic epidermal necrolysis that was initially diagnosed as a scald burn. Further anamnesis prompted by spread of the lesions during hospitalization revealed that the patient had been receiving ceftriaxone for several days. To the best of our knowledge, this is the first case of ceftriaxone-induced toxic epidermal necrolysis in the English literature. Conclusion Toxic epidermal necrolysis is an acute, life-threatening, exfoliative disorder with a high mortality rate. High clinical suspicion, prompt recognition, and initiation of supportive care is mandatory. Thorough investigation of the pathogenetic mechanisms is fundamental. Optimal treatment guidelines are still unavailable.

  4. Transplantation of autologous noncultured epidermal cell suspension in treatment of patients with stable vitiligo

    XU Ai-e; WEI Xiao-dong; CHENG Dong-qing; ZHOU He-fen; QIAN Guo-pei


    @@ Treatment of vitiligo by transplantation of noncultured melanocytes containing keratino-cytes has been successful since 1992,1 We report the encouraging results of autologous epidermal cell suspension in the treatment of 24 patients with stable vitiligo since 1998.

  5. Sustained complete remission of human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver during long-term trastuzumab (Herceptin maintenance therapy in a woman: a case report

    Tsavaris Nicolas


    Full Text Available Abstract Introduction This case report and short review discusses how long trastuzumab should be continued in metastatic breast cancer, the safety issues in case of pregnancy and the risk of relapse with trastuzumab cessation. Case presentation We present the case of a 34-year-old Caucasian woman with human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver who achieved prolonged complete remission within six months of receiving trastuzumab (Herceptin in combination with vinorelbine and gemcitabine. The patient remains in complete remission seven years later and continues to receive trastuzumab as maintenance therapy. Conclusion Trastuzumab-based therapies have greatly improved the survival rates of patients with human epidermal growth factor receptor 2- positive metastatic breast cancer. Despite such improvements, the safety of trastuzumab administration during pregnancy is yet to be defined.

  6. Necrotrophic fungi associated with epidermal microcracking caused by chilling injury in pickling cucumber fruit


    The objective of this work was to visualize the association between microcracking and other epidermal chilling injury symptoms, and to identify rots in cucumber fruit (Cucumis sativus L.) by scanning electron microscopy (SEM). Depressed epidermal areas and surface cracking due to damages of subepidermal cells characterized the onset of pitting in cucumber fruit. The germination of conidia of Alternaria alternata, with some of them evident on the fractures in the cultivar Trópico, occurred aft...

  7. Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration

    Oike, Yuichi; Yasunaga, Kunio; Ito, Yasuhiro; Matsumoto, Shun-ichiro; Maekawa, Hiromitsu; Morisada, Tohru; Arai, Fumio; Nakagata, Naomi; Takeya, Motohiro; Masuho, Yasuhiko; Suda, Toshio


    We report here the identification of an angiopoietin-related growth factor (AGF). To examine the biological function of AGF in vivo, we created transgenic mice expressing AGF in epidermal keratinocytes (K14-AGF). K14-AGF mice exhibited swollen and reddish ears, nose and eyelids. Histological analyses of K14-AGF mice revealed significantly thickened epidermis and a marked increase in proliferating epidermal cells as well as vascular cells in the skin compared with nontr...

  8. Epidermal differentiation complex yields a secret: mutations in the cornification protein filaggrin underlie ichthyosis vulgaris.

    Segre, Julia A


    Ichthyosis vulgaris (IV), characterized by mild scaling on limbs and lower abdomen, has an incidence of 1 in 250. Smith, McLean, and colleagues demonstrate that common mutations in filaggrin underlie IV. Filaggrin aggregates keratin intermediate filaments and is cross-linked into the cornified envelope to form the epidermal barrier. These findings reinforce the importance of the epidermal barrier in pathogenesis of skin diseases.

  9. Antimicrobial susceptibility of Staphylococcus hyicus isolated from exudative epidermitis in pigs.

    Wegener, H C; Watts, J.L.; Salmon, S A; Yancey, R J


    Exudative epidermitis or greasy pig syndrome is caused by the coagulase-variable staphylococcal species Staphylococcus hyicus. Treatment of this disease is problematic because of the limited number of antimicrobial agents available for this purpose. Thirteen antimicrobial agents were evaluated for their activities against 100 S. hyicus strains isolated from pigs with exudative epidermitis. Novobiocin was the most active compound tested, with an MIC for 90% of the strains tested (MIC90) of < o...

  10. Vulvar Epidermal Inclusion Cyst as a Long-term Complication of Female Genital Mutilation

    Ana Mercedes Victoria-Martínez; Laura Cubells-Sánchez; Lorena Martínez-Leborans; José Luis Sánchez-Carazo; Víctor Alegre de Miquel


    We present a case report of a patient with epidermal inclusion cyst as a late complication of female genital mutilation (FGM). We describe the management of the patient, and a review of the literature. We report the clinical and pathological findings in a 37-year-old female patient from Nigeria, with a clitoral mass of 1 year duration. She declared to have an FGM since she was 5 years. The lesion was excised successfully with good cosmetic results. Histological examination revealed epidermal ...

  11. Cephazolin-Induced Toxic Epidermal Necrolysis Treated with Intravenous Immunoglobulin and N-Acetylcysteine

    Carlos Saavedra


    Full Text Available Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. We report a case of cephazolin-induced toxic epidermal necrolysis treated with intravenous immunoglobulin and N-acetylcysteine with excellent response.

  12. Survival of environmental mycobacteria in Acanthamoeba polyphaga.

    Adékambi, Toïdi; Ben Salah, Skandar; Khlif, Mohamed; Raoult, Didier; Drancourt, Michel


    Free-living amoebae in water are hosts to many bacterial species living in such an environment. Such an association enables bacteria to select virulence factors and survive in adverse conditions. Waterborne mycobacteria (WBM) are important sources of community- and hospital-acquired outbreaks of nontuberculosis mycobacterial infections. However, the interactions between WBM and free-living amoebae in water have been demonstrated for only few Mycobacterium spp. We investigated the ability of a number (n = 26) of Mycobacterium spp. to survive in the trophozoites and cysts of Acanthamoeba polyphaga. All the species tested entered the trophozoites of A. polyphaga and survived at this location over a period of 5 days. Moreover, all Mycobacterium spp. survived inside cysts for a period of 15 days. Intracellular Mycobacterium spp. within amoeba cysts survived when exposed to free chlorine (15 mg/liter) for 24 h. These data document the interactions between free-living amoebae and the majority of waterborne Mycobacterium spp. Further studies are required to examine the effects of various germicidal agents on the survival of WBM in an aquatic environment.

  13. Toxic epidermal necrolysis: a severe cutaneous adverse drug reaction

    K. N. Chidananda


    Full Text Available Toxic epidermal necrolysis (TEN is a rare but serious is a rare but potentially life-threatening condition. It is primarily a cutaneous reaction to various precipitating agents, characterized by wide spread erythema and detachment of the epidermis from the dermis. Among the various cutaneous adverse drug reactions, TEN occupy a primary place in terms of mortality. In TEN large sheets of skin are lost from the body surface, thereby decreasing the protecting function of the skin, which results in complications. Usually, TEN is self-limited in absence of complications. If complicated by sepsis, there will be increased chances of mortality. The main treatment would be cessation of the causative drug and early admission of the patient for supportive care and minimizing the occurrence of complications. The present articles reviews the etiology, pathophysiology, differential diagnosis and treatment protocol, with a case of TEN occurrence in a child of 4 years age after consuming phenytoin syrup for febrile convulsions. [Int J Basic Clin Pharmacol 2015; 4(1.000: 1-5

  14. Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans.

    Van Buskirk, Cheryl; Sternberg, Paul W


    The epidermal growth factor receptor (EGFR)/ErbB receptor tyrosine kinases regulate several aspects of development, including the development of the mammalian nervous system. ErbB signaling also has physiological effects on neuronal function, with influences on synaptic plasticity and daily cycles of activity. However, little is known about the effectors of EGFR activation in neurons. Here we show that EGF signaling has a nondevelopmental effect on behavior in Caenorhabditis elegans. Ectopic expression of the EGF-like ligand LIN-3 at any stage induces a reversible cessation of feeding and locomotion. These effects are mediated by neuronal EGFR (also called LET-23) and phospholipase C-gamma (PLC-gamma), diacylglycerol-binding proteins, and regulators of synaptic vesicle release. Activation of EGFR within a single neuron, ALA, is sufficient to induce a quiescent state. This pathway modulates the cessation of pharyngeal pumping and locomotion that normally occurs during the lethargus period that precedes larval molting. Our results reveal an evolutionarily conserved role for EGF signaling in the regulation of behavioral quiescence.

  15. Intranasal epidermal growth factor treatment rescues neonatal brain injury

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


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

  16. Epidermal growth factor: a critical factor in fetal maturation?

    Thorburn, G D; Waters, M J; Young, I R; Dolling, M; Buntine, D; Hopkins, P S


    Epidermal growth factor (EGF) infused over 3-14 days into fetal sheep of 110-125 days gestation resulted in a number of morphological and endocrine changes. Striking hypertrophy of the skin, wool follicles and their accessory structures was seen, together with a reduction in the ratio of secondary to primary follicles and degenerative changes in wool fibres associated with shedding of fibres. Adrenal, thyroid, liver and kidney weights were increased while thymus weight was decreased. The increase in adrenal size resulted from cortical hypertrophy and was associated with increased cortisol secretion. Thyroid hypertrophy was accompanied by an increase in colloid stores, decreased plasma thyroxine and reverse triiodothyronine (T3) concentrations, unchanged plasma T3 and thyroid-binding globulin and raised thyrotropin (TSH) levels. Thyrotropin receptor affinity and content per gram of tissue were unchanged. Fetal and maternal plasma prolactin and growth hormone levels, and fetal plasma placental lactogen levels, were unchanged, although there was a significant rise in maternal plasma placental lactogen concentrations with high doses of EGF. Other maturational parameters such as switching from fetal to adult haemoglobin and liver glycogen content were unaffected.

  17. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF.

    Yonghua He

    Full Text Available Necrotizing enterocolitis (NEC is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF, typically found in bodily fluids, such as amniotic fluid, salvia and mother's breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N' terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.

  18. Shavenbaby couples patterning to epidermal cell shape control.

    Hélène Chanut-Delalande


    Full Text Available 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.

  19. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

    Yoshihiro Akimoto


    Full Text Available Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488. However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

  20. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes.

    Geetanjali Kharmate

    Full Text Available Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa. However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa.

  1. Human epidermal growth factor and the proliferation of human fibroblasts.

    Carpenter, G; Cohen, S


    The effect of human epidermal growth factor (hEGF), a 5,400 molecular weight polypeptide isolated from human urine, on the growth of human foreskin fibroblasts (HF cells) was studied by measuring cell numbers and the incorporation of labeled thymidine. The addition of hEGF to HF cells growing in a medium containing 10% calf serum resulted in a 4-fold increase in the final density. The presence of hEGF also promoted the growth of HF cells in media containing either 1% calf serum or 10% gamma globulin-free serum. The addition of hEGF to quiescent confluent monolayers of HF cells, maintained in a medium with 1% calf serum for 48 hours, resulted in a 10- to 20-fold increase in the amount of 3H-thymidine incorporation after 20-24 hours. The stimulation of thymidine incorporation was maximal at an hEGF concentration of 2 ng/ml, was dependent on the presence of serum, and was enhanced by the addition of ascorbic acid. In confluent cultures of HF cells, subject to density dependent inhibition of growth, hEGF was able to stimulate DNA synthesis more effectively than fresh calf serum. Human EGF stimulated DNA synthesis in quiescent cultures, however, regardless of cell density. The addition of rabbit anti-hEGF inhibited all effects of this growth factor on HF cells.

  2. Epidermal growth factor mediates spermatogonial proliferation in newt testis

    Abé Shin-ichi


    Full Text Available Abstract The complex processes of spermatogenesis are regulated by various factors. The aim of the current study is to determine the effect of epidermal growth factor (EGF on spermatogonial proliferation and clarify the mechanism causing the proliferation in newt testis. In the organ culture, EGF stimulated spermatogonial proliferation, but not their differentiation into spermatocytes. cDNA cloning identified 3 members of the EGF receptors, ErbB1, ErbB2, and ErbB4, in the testis. RT-PCR showed that all the receptors cloned were expressed in both Sertoli and germ cells at the spermatogonial stage. In the organ cultures with inhibitors for the EGF receptors, mitogen-activated protein kinase (MAPK, and phosphoinositide 3-kinase (PI3K, the EGF-induced spermatogonial proliferation was suppressed. Furthermore, when the organ culture was exposed to EGF, the expressions of stem cell factor (SCF, immunoglobulin-like domain containing neuregulin1 (Ig-NRG1, and ErbB4 mRNA were increased. These results suggested that, since the spermatogonia are sequestered within cysts by the blood-testis barrier consisted of Sertoli cells, EGF possibly mediates spermatogonial proliferation in an endocrine manner through the receptors including ErbB1, ErbB2, and ErbB4 expressed on Sertoli cells via activation of MAPK cascade or/and PI3K cascade by elevating the expressions of SCF, Ig-NRG1, and ErbB4.

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

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


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

  4. Expression of epidermal growth factor receptors in human brain tumors.

    Libermann, T A; Razon, N; Bartal, A D; Yarden, Y; Schlessinger, J; Soreq, H


    The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.

  5. Verrucous hemangioma with pseudoepitheliomatous epidermal hyperplasia in an adult horse.

    Pérez-Écija, A; Estepa, J C; Barranco, I; Rodríguez-Gómez, I M; Mendoza, F J; Gómez-Laguna, J


    Verrucous hemangiomas are a rare specific variant of equine skin tumors not well described in the literature. An 8-year-old gelding presented a unilateral lesion on the pastern. Macroscopically, the mass showed a warty and verrucous surface with focal ulcerations. The histology showed a dermal proliferation of endothelial-layered capillaries and venules separated by a delicate stroma of scant fibroblasts and collagen deposition, with pseudoepitheliomatous hyperplasia (exuberant reactive irregular epithelial hyperplasia with tongue-like projections extending into the dermis, mimicking downgrowth of squamous cell carcinoma) and orthokeratotic hyperkeratosis of the overlying epidermis. The immunohistochemical study confirmed the endothelial origin of the tumor, and a final diagnosis of verrucous hemangioma with pseudoepitheliomatous hyperplasia was confirmed. To the knowledge of the authors, this is the first detailed description of this entity in adult horses. Moreover, the clinical progression and epidermal changes have not been previously reported, emphasizing the importance of a pathological study of any epithelial preneoplastic lesion to rule out an underlying dermal neoplasia. © The Author(s) 2013.

  6. Early radiographic response to epidermal growth factor receptor-tyrosine kinase inhibitor in non-small cell lung cancer patients with epidermal growth factor receptor mutations: A prospective study

    John WC Chang


    Full Text Available Background: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI in non-small cell lung cancer (NSCLC patients are still ill-defined. Methods: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS, overall survival (OS, and toxicity profile were assessed prospectively. Results: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4% achieved partial response (PR. Twenty-one patients (21/39, 53.8% had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29. Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months and OS (18.3 months of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively. But the survival differences were statistically non-significant. Conclusions: A very high percentage (72.4%, 21/29 of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

  7. Ex vivo differentiation of multipotent adult progenitor cells to skin epidermal cells

    Ji Kaihong; Xiong Jun; Fan Lixing; Hu Kaimeng; Liu Houqi


    Objective: By establishing the indirect contact co-culture system, we studied the in vitro condition for MAPCs differentiating into epidermal cells and the transformation of MAPCs into epidermal cell phenotype. Methods: Cell culture insert membrane was used for substitute basal membrane and MAPCs, fibroblast cells (FCs) and mixture of MAPCs and epidermal cells and FCs were separately implanted into 2 sides of it. PKH26 was used to label cloned MAPCs; type Ⅳ collagen rapid adhering method was used to isolate and culture the skin epidermal cells from 1-day-old SD rat. Results: Part of the MAPCs transformed into cells expressing keratin in the presence of peripheral epithelia and FCs. Type Ⅳ collagen rapid adhering method successfully selected rats' epidermal stem cells. The mixture of the 2 kinds of cells or indirect culture might promote the differentiation through mesenchymal factors secreted by dermis FC. Conclusion: We were the first to have established the in vitro model of MAPCs differentiation into epidermal cells, in which MAPCs were transformed into epithelium-like cells.

  8. Evolution of the clonogenic potential of human epidermal stem/progenitor cells with age

    Zobiri O


    Full Text Available Olivia Zobiri, Nathalie Deshayes, Michelle Rathman-JosserandDepartment of Biological Research, L'Oréal Advanced Research, Clichy Cedex, FranceAbstract: A number of clinical observations have indicated that the regenerative potential and overall function of the epidermis is modified with age. The epidermis becomes thinner, repairs itself less efficiently after wounding, and presents modified barrier function recovery. In addition, the dermal papillae flatten out with increasing age, suggesting a modification in the interaction between epidermal and dermal compartments. As the epidermal regenerative capacity is dependent upon stem and progenitor cell function, it is naturally of interest to identify and understand age-related changes in these particular keratinocyte populations. Previous studies have indicated that the number of stem cells does not decrease with age in mouse models but little solid evidence is currently available concerning human skin. The objective of this study was to evaluate the clonogenic potential of keratinocyte populations isolated from the epidermis of over 50 human donors ranging from 18 to 71 years old. The data indicate that the number of epidermal cells presenting high regenerative potential does not dramatically decline with age in human skin. The authors believe that changes in the microenvironment controlling epidermal basal cell activity are more likely to explain the differences in epidermal function observed with increasing age.Keywords: skin, epidermal stem cells, aging, colony-forming efficiency test

  9. The increasing role of epidermal grafting utilizing a novel harvesting system in chronic wounds.

    Serena, Thomas E


    Skin grafting techniques range from harvesting full-thickness to split-thickness grafts to grafts containing only epidermis. All of these autologous tissues have their place on the reconstructive ladder. However, the use of full-thickness and split-thickness grafts as coverage over chronic wounds remains limited by a number of factors, including the need for anesthesia, a surgically trained physician, and an operating room in which to perform the procedure; pain and damage associated with the donor site; and severe patient comorbidities. Epidermal grafting offers an option for autografts and uses only a minimal amount of superficial epidermis from the donor site. Although successful use of epidermal grafting has been reported in pigmentation disorders, as well as burns and chronic wounds, previous harvesting methods have been described as cumbersome and time consuming. An automated epidermal harvesting system is now commercially available and involves a tool that applies both heat and suction concurrently to normal skin to induce epidermal micrograft formation. The new tool allows quick harvest and transfer of the epidermal micrografts at the bedside without anesthesia, with minimal donor site healing time and patient discomfort. The use of epidermal grafts in chronic wounds and the harvesting technique are reviewed here.

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

    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


    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. 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). 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. 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. Copyright © 2014 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  11. Streptococcus induces circulating CLA(+) memory T-cell-dependent epidermal cell activation in psoriasis.

    Ferran, Marta; Galván, Ana B; Rincón, Catalina; Romeu, Ester R; Sacrista, Marc; Barboza, Erika; Giménez-Arnau, Ana; Celada, Antonio; Pujol, Ramon M; Santamaria-Babí, Luis F


    Streptococcal throat infection is associated with a specific variant of psoriasis and with HLA-Cw6 expression. In this study, activation of circulating psoriatic cutaneous lymphocyte-associated antigen (CLA)(+) memory T cells cultured together with epidermal cells occurred only when streptococcal throat extracts were added. This triggered the production of Th1, Th17, and Th22 cytokines, as well as epidermal cell mediators (CXCL8, CXCL9, CXCL10, and CXCL11). Streptococcal extracts (SEs) did not induce any activation with either CLA(-) cells or memory T cells cultured together with epidermal cells from healthy subjects. Intradermal injection of activated culture supernatants into mouse skin induced epidermal hyperplasia. SEs also induced activation when we used epidermal cells from nonlesional skin of psoriatic patients with CLA(+) memory T cells. Significant correlations were found between SE induced upregulation of mRNA expression for ifn-γ, il-17, il-22, ip-10, and serum level of antistreptolysin O in psoriatic patients. This study demonstrates the direct involvement of streptococcal infection in pathological mechanisms of psoriasis, such as IL-17 production and epidermal cell activation.

  12. Sensitivity enhancement of a micro-scale biomimetic tactile sensor with epidermal ridges

    Zhang, Yuhua


    A microscale biomimetic tactile sensor with epidermal ridges is proposed to enhance the sensitivity of force detection. Guided by the principles of the human tactile perception mechanism, specifically the epidermal ridges, artificial epidermal ridges made of polydimethylsiloxane (PDMS) were designed and placed on micro-fabricated metal strain gauge arrays. A polyimide layer was fabricated to facilitate attachment between the metal and PDMS, so that patterned copper could be deposited on the polyimide to function as the strain gauges. The aspect ratio of the artificial epidermal ridges was optimized using material stability calculations and finite element method (FEM) simulations, and the optimal structure obtained was 400 µm in width and 110 µm in height. Experiments verified the effectiveness of enhancing the sensitivity of such a tactile sensor with the artificial epidermal ridges, in that the outputs of the strain gauges were 1.8 times more sensitive than those of a tactile sensor without ridges. The proposed artificial epidermal ridges are readily applicable to any developed tactile sensors for performance enhancement.

  13. Epidermal growth factor treatment of the adult brain subventricular zone leads to focal microglia/macrophage accumulation and angiogenesis.

    Lindberg, Olle R; Brederlau, Anke; Kuhn, H Georg


    One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  14. The role of group size and environmental factors on survival in a cooperatively breeding tropical passerine

    Richardson, David S.; Eikenaar, Cas; Komdeur, Jan


    1. Variation in survival, a major determinant of fitness, may be caused by individual or environmental characteristics. Furthermore, interactions between individuals may influence survival through the negative feedback effects of density dependence. Compared to species in temperate regions, we have

  15. Surviving Women's Learning Experiences from the Tsunami in Aceh

    Teng, Yan Fang Jane; Yusof, Qismullah


    This study investigated surviving women's learning experiences from the 2004 tsunami in Aceh. Women were the majority of casualties and the most vulnerable after the tsunami. Almost a decade later, we used a conceptual framework of experiential learning, critical reflection, and transformative learning to understand the surviving women's ways of…

  16. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

    Palmer, Colin N A; Irvine, Alan D; Terron-Kwiatkowski, Ana


    Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although...

  17. Survivable Local Area Network.

    Enhanced availability and survivability of communications between geographically remote locations with a minimum of redundancy of transmission...isolate bus segements on either side of a connection so that if a fault occurs only the segment containing the fault will be affected. The first type

  18. Survivability via Control Objectives



    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  19. Flexible survival regression modelling

    Cortese, Giuliana; Scheike, Thomas H; Martinussen, Torben


    Regression analysis of survival data, and more generally event history data, is typically based on Cox's regression model. We here review some recent methodology, focusing on the limitations of Cox's regression model. The key limitation is that the model is not well suited to represent time-varyi...

  20. A Profile of Survival.

    Zimrin, Hanita


    Abused children who survived the trauma of their childhood and grew up to be well-adjusted were compared with a matched group who showed a high degree of psychosocial pathology. The variables which distinguished the two groups were fatalism, self-esteem, cognitive abilities, self-destructiveness, hope and fantasy, behavior patterns and external…

  1. Network ties and survival

    Acheampong, George; Narteh, Bedman; Rand, John


    of the SCPFs in Ghana. Distribution ties are associated with negative survival chances and this is not even reversed if the human capital of the owner increases although managers with higher human capital and higher distribution ties experience positive effects. Industry ties are associated with positive ties...

  2. Fighting for their survival

    Gracie; Guo


    The analysis of economic performance of China’s painting&dyeing industry during the first five months of 2008 Relying on the researches on enterprises,China Dyeing and Printing Association works out the industry performance in the first five months this year.According to the results,painting&dyeing firms are fighting for their survival in 2008 with yuan appreciation,

  3. Artists’ Survival Rate

    Bille, Trine; Jensen, Søren


    The literature of cultural economics generally finds that an artistic education has no significant impact on artists’ income and careers in the arts. In our research, we have readdressed this question by looking at the artists’ survival in the arts occupations. The results show that an artistic...... education has a significant impact on artists’ careers in the arts and we find important industry differences....

  4. Crossover studies with survival outcomes.

    Buyze, Jozefien; Goetghebeur, Els


    Crossover designs are well known to have major advantages when comparing the effect of two treatments which do not interact. With a right-censored survival endpoint, however, this design is quickly abandoned in favour of the more costly parallel design. Motivated by human immunodeficiency virus (HIV) prevention studies which lacked power, we evaluate what may be gained in this setting and compare parallel with crossover designs. In a heterogeneous population, we find and explain a substantial increase in power for the crossover study using a non-parametric logrank test. With frailties in a proportional hazards model, crossover designs equally lead to substantially smaller variance for the subject-specific hazard ratio (HR), while the population-averaged HR sees negligible gain. Its efficiency benefit is recovered when the population-averaged HR is reconstructed from estimated subject-specific hazard rates. We derive the time point for treatment crossover that optimizes efficiency and end with the analysis of two recent HIV prevention trials. We find that a Cellulose sulphate trial could have hardly gained efficiency from a crossover design, while a Nonoxynol-9 trial stood to gain substantial power. We conclude that there is a role for effective crossover designs in important classes of survival problems.

  5. Breast cancer survival in Germany: a population-based high resolution study from Saarland.

    Holleczek, Bernd; Jansen, Lina; Brenner, Hermann


    Population-based survival studies of breast cancer patients are commonly restricted to age- and stage-specific analyses. This study from Germany aimed at extending available population-based survival data on further prognostic cancer characteristics such as tumor grade, hormone receptor status and human epidermal growth factor receptor type 2 (HER2/neu) expression. Data from the population-based Saarland Cancer Registry including female patients diagnosed with invasive breast cancer between 2000 and 2009 were included. Period analysis methodology and regression modelling were used to obtain estimates of 5-year relative survival and tumor related excess risks in 2005-2009. Overall age standardized 5-year relative survival was 83%. In addition to age and stage, tumor grade and hormone receptor status were independent predictors of 5-year relative survival. Detailed analyses by age, stage, morphology, tumor grade, hormone receptor status and HER2/neu expression consistently revealed lower survival of patients with high grade, hormone receptor negative or HER2/neu positive cancers and patients aged 70 years or older. This high resolution study extends available population-based survival data of breast cancer patients. Particular efforts should be made to overcome the persisting large survival deficits, which were observed for elderly patients in all clinical subgroups.

  6. Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2

    LI Hui-ping; XIAO Yu; WANG You-fan; L(U) You-yong; SUN Yan; JI Jia-fu; HOU Kuan-yong; LEI Yu-tao; ZHAO Hong-mei; WANG Jing; ZHENG Jie; LIU Jian-ying; WANG Mo-pei


    Background Human epidermal growth factor 2 (HER2) is one of the most important prediction factors, but only 25%-30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients.This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients.Methods Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2. and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis.Results Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods (P=0.047 and P=0.05, respectively). Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index (kappa=0.37), allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69-2.74 fold.Conclusions Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.

  7. Human epidermal growth factor receptor-2 in oesophageal cancers: An observational study

    Hazem Al-Momani; Rachel Barnes; Ahmed El-Hadi; Rachit Shah; Wyn G Lewis; Paul Edwards


    AIM:To determine the incidence of human epidermal growth factor receptor 2 (HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative"for HER2; those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colour in situ hybridisations (HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66years (range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was; upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases; seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21 (84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3or more (13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases

  8. Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer

    Sobani, Zain A; Sawant, Ashwin; Jafri, Mikram; Correa, Amit Keith; Sahin, Ibrahim Halil


    Epidermal growth factor receptor (EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer (CRC). Evidence from clinical trials indicates that cetuximab and panitumumab (anti-EGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS (KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade. PMID:27777877

  9. Factors influencing patient and graft survival in 300 cadaveric pediatric renal transplants.

    Churchill, B M; Sheldon, C A; McLorie, G A; Arbus, G S


    We reviewed the results of 300 cadaveric pediatric renal transplantations performed at our institution. The procedures provided significant survival and improvement of the quality of life in the majority of children. Recipient and graft survival was better in patients more than 5 years old than in younger children. Early nontechnical thrombosis was a major specific problem in young recipients. The original disease did affect graft survival. Uncorrected congenital bladder storage and micturition inefficiency adversely affected graft survival.

  10. Fatty acid metabolism studies of human epidermal cell cultures.

    Marcelo, C L; Dunham, W R


    Adult human epidermal keratinocytes grow rapidly in medium that is essential fatty acid (EFA)-deficient. In this medium they exhibit decreased amounts of the fatty acids, 18:2, 20:3, 20:4, and contain increased amounts of monounsaturated fatty acids. [14C]- and [3H]acetate and radiolabeled fatty acids, 16:0, 18:2, and 20:4 were used to study the fatty acid metabolism of these cells. Label from acetate appeared in 14- to 20-carbon fatty acids, both saturated and monounsaturated. No label was seen in the essential fatty acid 18:2, 18:3, and 20:4. Radiolabel from [9, 10-3H]palmitic acid (16:0) was detected in 16:0, 16:1, 18:0, and 18:1. [14C]linoleic acid (18:2) was converted to 18:3, 20:2, 20:3, and 20:4, demonstrating delta 6 and delta 5 desaturase activity in keratinocytes. Label from acetate, 16:0, or 18:2 was found mostly in the cellular phospholipids while only one third of the label from [14C]arachidonic was found in the phospholipids. [14C]acetate and [14C]18:2 time course data were used to construct a model of the metabolism of these reactants, using coupled, first-order differential equations. The data show that EFA-deficient keratinocytes metabolize fatty acids using pathways previously found in liver; they suggest the positioning of 18:2 desaturase and 18:3 elongase near the plasma membrane; they indicate that for the synthesis of nonessential fatty acids the formation of 18:0 from 16:0 is the rate-determining step; and they show that the conversion of 18:2 to 20:3 is rapid. These experiments demonstrate a method to study lipid enzyme kinetics in living cells.

  11. BCDC Major Permits

    California Department of Resources — Data depicts the majority of the major permits that BCDC has issued. Data has been created by a team of interns and staff and has been digitized using maps provided...

  12. Major Sport Venues

    Department of Homeland Security — The Major Public Venues dataset is composed of facilities that host events for the National Association for Stock Car Auto Racing, Indy Racing League, Major League...

  13. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro

    GAO Nan; CUI GuangHui; WANG ZhiChong; HUANG Bing; GE Jian; LU Rong; ZHANG KeFei; FAN ZhiGang; LU Li; PENG Zhan


    Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epidermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immunohistology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epidermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being cocultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

  14. Evaluation of emulsion electrospun polycaprolactone/hyaluronan/epidermal growth factor nanofibrous scaffolds for wound healing.

    Wang, Zhenbei; Qian, Yuna; Li, Linhao; Pan, Lianhong; Njunge, Lucy W; Dong, Lili; Yang, Li


    Wound healing scaffolds provide cells with structural integrity and can also deliver biological agents to establish a skin tissue-specific microenvironment to regulate cell functions and to accelerate the healing process. In this study, we fabricated biodegradable nanofibrous scaffolds with an emulsion electrospinning technique. The scaffolds were composed of polycaprolactone, hyaluronan and encapsulating epidermal growth factor. The morphology and core-sheath structure of the nanofibers were characterized by scanning electron microscopy and transmission electron microscopy. The scaffolds were also characterized for chemical composition and hydrophilicity with a Fourier-transform infrared analysis, energy dispersive spectroscopy and the water contact angle. An in vitro model protein bovine serum albumin and epidermal growth factor release study was conducted to evaluate the sustained release potential of the core-sheath structured nanofibers with and without the hyaluronan component. Additionally, an in vitro cultivation of human skin keratinocytes (HaCaT) and fibroblasts on polycaprolactone/hyaluronan and polycaprolactone/hyaluronan-epidermal growth factor scaffolds showed a significant synergistic effect of hyaluronan and epidermal growth factor on cell proliferation and infiltration. Furthermore, there was an up-regulation of the wound-healing-related genes collagen I, collagen III and TGF-β in polycaprolactone/hyaluronan/epidermal growth factor scaffolds compared with control groups. In the full-thickness wound model, the enhanced regeneration of fully functional skin was facilitated by epidermal regeneration in the polycaprolactone/hyaluronan/epidermal growth factor treatment group. Our findings suggest that bioactivity and hemostasis of the hyaluronan-based nanofibrous scaffolds have the capability to encapsulate and control the release of growth factors that can serve as skin tissue engineering scaffolds for wound healing.

  15. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro


    Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epi-dermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immuno-histology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epi-dermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being co-cultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

  16. Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.

    Cripps, C; Winquist, E; Devries, M C; Stys-Norman, D; Gilbert, R


    What are the benefits associated with the use of anti-epidermal growth factor receptor (anti-EGFR) therapies in squamous cell carcinoma of the head and neck (HNSCC)? Anti-EGFR therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab. Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract. The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx. Worldwide, HNSCC is the sixth most common neoplasm, and despite advances in therapy, long-term survival in HNSCC patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages III-IVB) HNSCC; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years. Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced HNSCC and as monotherapy for patients with recurrent or metastatic (stage IVC) HNSCC who have progressed on platinum-based therapy. Given the interest in anti-EGFR agents in advanced HNSCC, the Head and Neck Cancer Disease Site Group (DSG) of Cancer Care Ontario's Program in Evidence-Based Care (PEBC) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment. Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-EGFR therapies. The medline, embase, and Cochrane Library databases, the American Society of Clinical Oncology online conference proceedings, the Canadian Medical Association InfoBase, and the National Guidelines Clearinghouse were systematically searched to

  17. Survival analysis models and applications

    Liu, Xian


    Survival analysis concerns sequential occurrences of events governed by probabilistic laws.  Recent decades have witnessed many applications of survival analysis in various disciplines. This book introduces both classic survival models and theories along with newly developed techniques. Readers will learn how to perform analysis of survival data by following numerous empirical illustrations in SAS. Survival Analysis: Models and Applications: Presents basic techniques before leading onto some of the most advanced topics in survival analysis.Assumes only a minimal knowledge of SAS whilst enablin

  18. Thalassaemia major and the heart

    J. Malcolm Walker


    Full Text Available Disorders of haemoglobin synthesis are the commonest monogenetic disorders worldwide. When first described, thalassaemia was universally fatal in childhood, but after the adoption of regular blood transfusion survival until early teenage and adulthood was to be expected. At that stage in the life of these affected individuals organ failure followed, due to accumulated iron, for which the human has no excretory capacity. Principal amongst the tissues affected by iron overload is the heart and even to the present day, heart disease accounts for the overwhelming majority of premature deaths in this population. Managing transfusion derived iron overload was the next hurdle for clinicians and the families of the patients. For nearly four decades the only available treatment was the demanding regime of parenteral chelation therapy, required on a daily basis, to achieve growth, development and survival with limited or no organ damage. Despite the adoption of these treatment strategies the outlook for thalassaemia patients remained poor, with a 30% to 40% mortality occurring between late teenage and 30 years of age, even in well organised health care systems, such as in the UK, where regular transfusion and desferioxamine treatment were readily available. This dreadful early mortality, largely as a consequence of myocardial iron overload, (1,2 is now improving so that in the UK and other developed nations, heart failure in thalassaemic patients has become uncommon and premature death a much rarer tragedy. This editorial reviews, from a personal viewpoint of a cardiologist involved in the care of these patients for the last 20 years, the progress in the management of the cardiovascular complications of thalassaemia major (TM, which has followed better techniques of identifying those thalassaemic individuals at greatest risk, improved chelation strategies making best use of the three chelating agents that are now available and improved co

  19. Do signal transduction cascades influence survival in triple-negative breast cancer? A preliminary study

    Mumm, Jan-Niclas; Kölbl, Alexandra C; Jeschke, Udo; Andergassen, Ulrich


    Background Triple-negative breast cancer (TNBC) is a rather aggressive form of breast cancer, comprised by early metastasis formation and reduced overall survival of the affected patients. Steroid hormone receptors and the human epidermal growth factor receptor 2 are not overexpressed, limiting therapeutic options. Therefore, new treatment options have to be investigated. The aim of our preliminary study was to detect coherences between some molecules of intracellular signal transduction pathways and survival of patients with TNBC, in order to obtain some hints for new therapeutical solutions. Methods Thirty-one paraffin-embedded tumor tissue samples, which were determined to be negative for steroid hormone receptors as well as human epidermal growth factor receptor 2, were immunohistochemically stained for a number of signal transduction molecules from several signaling pathways. β-Catenin, HIF1α, MCL, Notch1, LRP6, XBP1, and FOXP3 were stained with specific antibodies, and their staining was correlated with patient survival by Kaplan–Meier analyses. Results Only two of the investigated molecules have shown correlation with overall survival. Cytoplasmic staining of HIF1α and centro-tumoral lymphocyte FOXP3 staining showed statistically significant correlations with survival. Conclusion The coherence of signal transduction molecules with survival of patients with TNBC is still controversially discussed in the literature. Our study comprises one more mosaic stone in the elucidation of these intracellular processes and their influences on patient outcome. Lots of research still has to be done in this field, but it would be worthwhile as it may offer new therapeutic targets for a group of patients with breast cancer, which is still hard to treat. PMID:27307757

  20. Pigmented epidermal cyst with dense collection of melanin: A rare entity - Report of a case with review of the literature.

    Jayalakshmy, P S; Subitha, K; Priya, P V; Johnson, Gerald


    Epidermal cyst is a very common benign cystic lesion of the skin. It is usual to find ulceration of the lining epithelium, rupture of the cyst wall with chronic inflammation and foreign body giant cell reaction. But, it is very rare to see an epidermal cyst with marked accumulation of melanin pigment. Only a few cases of pigmented epidermal cyst with dense collection of melanin pigment have been published in the literature. Here, we are reporting a case of ruptured epidermal cyst with keratin granuloma formation and showing dense collection of melanin pigment.

  1. Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model.

    Santa Maria, Peter Luke; Weierich, Kendall; Kim, Sungwoo; Yang, Yunzhi Peter


    That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model. A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle. The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks. The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration. This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

  2. Protective Effect of HemoHIM on Epidermal Melanocytes in Ultraviolet-B irradiated Mice

    Lee, Hae June [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Kim, Jong Choon; Moon, Chang Jong; Kim, Sung Ho [Chonnam National University, Gwangju (Korea, Republic of); Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Jeongeup Campus of Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Jang, Jong Sik; Kim, Tae Hwan [Kyungpook National University, Daegu (Korea, Republic of)


    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet-B (UV-B) irradiation, and observed the effect of an herbal preparation (HemoHIM, HH) on the formation, and decrease of UV-B-induced epidermal melanocytes. C57BL/6 mice were irradiated by UV-B 80 mJ:cm{sup -2} (0.5 mW:sec{sup -1}) daily for 7 days, and HH was intraperitoneally, orally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 13∼15 melanocytes:mm{sup -2}, and one week after UV irradiation, the applied areas showed an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal, oral or topical treatment with HH before each irradiation interrupted UV-B-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UV-B-irradiated, untreated control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with HH at 3rd and 6th weeks after irradiation. The present study suggests the HH as inhibitor of UV-B-induced pigmentation, and depigmenting agent.

  3. Homologs of SCAR/WAVE complex components are required for epidermal cell morphogenesis in rice.

    Zhou, Wenqi; Wang, Yuchuan; Wu, Zhongliang; Luo, Liang; Liu, Ping; Yan, Longfeng; Hou, Suiwen


    Filamentous actins (F-actins) play a vital role in epidermal cell morphogenesis. However, a limited number of studies have examined actin-dependent leaf epidermal cell morphogenesis events in rice. In this study, two recessive mutants were isolated: less pronounced lobe epidermal cell2-1 (lpl2-1) and lpl3-1, whose leaf and stem epidermis developed a smooth surface, with fewer serrated pavement cell (PC) lobes, and decreased papillae. The lpl2-1 also exhibited irregular stomata patterns, reduced plant height, and short panicles and roots. Molecular genetic studies demonstrated that LPL2 and LPL3 encode the PIROGI/Specifically Rac1-associated protein 1 (PIR/SRA1)-like and NCK-associated protein 1 (NAP1)-like proteins, respectively, two components of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (SCAR/WAVE) regulatory complex involved in actin nucleation and function. Epidermal cells exhibited abnormal arrangement of F-actins in both lpl2 and lpl3 expanding leaves. Moreover, the distorted trichomes of Arabidopsis pir could be partially restored by an overexpression of LPL2 A yeast two-hybrid assay revealed that LPL2 can directly interact with LPL3 in vitro Collectively, the results indicate that LPL2 and LPL3 are two functionally conserved homologs of the SCAR/WAVE complex components, and that they play an important role in controlling epidermal cell morphogenesis in rice by organising F-actin.

  4. Ultrastructure of the Epidermal Cell Wall and Cuticle of Tomato Fruit (Solanum lycopersicum L.) during Development.

    Segado, Patricia; Domínguez, Eva; Heredia, Antonio


    The epidermis plays a pivotal role in plant development and interaction with the environment. However, it is still poorly understood, especially its outer epidermal wall: a singular wall covered by a cuticle. Changes in the cuticle and cell wall structures are important to fully understand their functions. In this work, an ultrastructure and immunocytochemical approach was taken to identify changes in the cuticle and the main components of the epidermal cell wall during tomato fruit development. A thin and uniform procuticle was already present before fruit set. During cell division, the inner side of the procuticle showed a globular structure with vesicle-like particles in the cell wall close to the cuticle. Transition between cell division and elongation was accompanied by a dramatic increase in cuticle thickness, which represented more than half of the outer epidermal wall, and the lamellate arrangement of the non-cutinized cell wall. Changes in this non-cutinized outer wall during development showed specific features not shared with other cell walls. The coordinated nature of the changes observed in the cuticle and the epidermal cell wall indicate a deep interaction between these two supramolecular structures. Hence, the cuticle should be interpreted within the context of the outer epidermal wall. © 2016 American Society of Plant Biologists. All Rights Reserved.

  5. Serum response factor controls transcriptional network regulating epidermal function and hair follicle morphogenesis.

    Lin, Congxing; Hindes, Anna; Burns, Carole J; Koppel, Aaron C; Kiss, Alexi; Yin, Yan; Ma, Liang; Blumenberg, Miroslav; Khnykin, Denis; Jahnsen, Frode L; Crosby, Seth D; Ramanan, Narendrakumar; Efimova, Tatiana


    Serum response factor (SRF) is a transcription factor that regulates the expression of growth-related immediate-early, cytoskeletal, and muscle-specific genes to control growth, differentiation, and cytoskeletal integrity in different cell types. To investigate the role for SRF in epidermal development and homeostasis, we conditionally knocked out SRF in epidermal keratinocytes. We report that SRF deletion disrupted epidermal barrier function leading to early postnatal lethality. Mice lacking SRF in epidermis displayed morphogenetic defects, including an eye-open-at-birth phenotype and lack of whiskers. SRF-null skin exhibited abnormal morphology, hyperplasia, aberrant expression of differentiation markers and transcriptional regulators, anomalous actin organization, enhanced inflammation, and retarded hair follicle (HF) development. Transcriptional profiling experiments uncovered profound molecular changes in SRF-null E17.5 epidermis and revealed that many previously identified SRF target CArG box-containing genes were markedly upregulated in SRF-null epidermis, indicating that SRF may function to repress transcription of a subset of its target genes in epidermis. Remarkably, when transplanted onto nude mice, engrafted SRF-null skin lacked hair but displayed normal epidermal architecture with proper expression of differentiation markers, suggesting that although keratinocyte SRF is essential for HF development, a cross-talk between SRF-null keratinocytes and the surrounding microenvironment is likely responsible for the barrier-deficient mutant epidermal phenotype.

  6. In situ visualization of intracellular morphology of epidermal cells using stimulated Raman scattering microscopy

    Egawa, Mariko; Tokunaga, Kyoya; Hosoi, Junichi; Iwanaga, Shinya; Ozeki, Yasuyuki


    Visualization of epidermal cells is important because the differentiation patterns of keratinocytes (KCs) are considered to be related to the functions and condition of skin. Optical microscopy has been widely used to investigate epidermal cells, but its applicability is still limited because of the need for sample fixation and staining. Here, we report our staining-free observation of epidermal cells in both tissue and culture by stimulated Raman scattering (SRS) microscopy that provides molecular vibrational contrast. SRS allowed us to observe a variety of cellular morphologies in skin tissue, including ladder-like structures in the spinous layer, enucleation of KCs in the granular layer, and three-dimensional cell column structures in the stratum corneum. We noticed that some cells in the spinous layer had a brighter signal in the cytoplasm than KCs. To examine the relevance of the observation of epidermal layers, we also observed cultured epidermal cells, including KCs at various differentiation stages, melanocytes, and Langerhans cell-like cells. Their SRS images also demonstrated various morphologies, suggesting that the morphological differences observed in tissue corresponded to the cell lineage. These results indicate the possible application of SRS microscopy to dermatological investigation of cell lineages and types in the epidermis by cellular-level analysis.

  7. Evolution of the clonogenic potential of human epidermal stem/progenitor cells with age.

    Zobiri, Olivia; Deshayes, Nathalie; Rathman-Josserand, Michelle


    A number of clinical observations have indicated that the regenerative potential and overall function of the epidermis is modified with age. The epidermis becomes thinner, repairs itself less efficiently after wounding, and presents modified barrier function recovery. In addition, the dermal papillae fatten out with increasing age, suggesting a modification in the interaction between epidermal and dermal compartments. As the epidermal regenerative capacity is dependent upon stem and progenitor cell function, it is naturally of interest to identify and understand age-related changes in these particular keratinocyte populations. Previous studies have indicated that the number of stem cells does not decrease with age in mouse models but little solid evidence is currently available concerning human skin. The objective of this study was to evaluate the clonogenic potential of keratinocyte populations isolated from the epidermis of over 50 human donors ranging from 18 to 71 years old. The data indicate that the number of epidermal cells presenting high regenerative potential does not dramatically decline with age in human skin. The authors believe that changes in the microenvironment controlling epidermal basal cell activity are more likely to explain the differences in epidermal function observed with increasing age.



    Objective: To investigate the mechanism of the effect of Moist Exposed Burn Therapy (MEBT) and Moist Exposed Burn Ointment (MEBO) on the spontaneous repair and healing of superficial third degree burn wound involving fatty layer. Method: A series of skin tissue samples were taken from deep burn wounds of 2 cases. Immunocytochemistry method, biotin avidin DCS system, and indirect immunofluorescence technique were applied. Mouse anti human keratin type 19 monoclonal antibody was used to detect regenerative epidermal stem cells in wound tissues. Results: Epidermal regenerative stem cells emerged at 24 hours post burn, and the number of epidermal regenerative stem cell increased on day 4 post burn. On days 7 and 14 post burn, the number of epidermal stem cells increased to the peak level. On days 21 and 28 post burn, it decreased and disappeared gradually as burn wound progressed to healing. Conclusion: MEBT/MEBO has the effect of promoting the activation and proliferation of epidermal regenerative stem cells in the residual viable tissue of superficial full thickness burn wound, and these stem cells play an unique role in spontaneous wound healing of deep burn.

  9. From diffuse growth to planar polarity in Arabidopsis root epidermal cells

    Daria eBalcerowicz


    Full Text Available Plant roots fulfill important functions as they serve in water and nutrient uptake, provide anchorage of the plant body in the soil and in some species form the site of symbiotic interactions with soil-living biota. Root hairs, tubular-shaped outgrowths of specific epidermal cells, significantly increase the root's surface area and aid in these processes. In this review we focus on the molecular mechanisms that determine the hair and non-hair cell fate of epidermal cells and that define the site on the epidermal cell where the root hair will be initiated (= planar polarity determination. In the model plant Arabidopsis, trichoblast and atrichoblast cell fate results from intra- and intercellular position-dependent signaling and from complex feedback loops that ultimately regulate GL2 expressing and non-expressing cells. When epidermal cells reach the end of the root expansion zone, root hair promoting transcription factors dictate the establishment of polarity within epidermal cells followed by the selection of the root hair initiation site at the more basal part of the trichoblast. Molecular players in the abovementioned processes as well as the role of phytohormones are discussed, and open areas for future experiments are identified.

  10. Nicotinic acid receptor abnormalities in human skin cancer: implications for a role in epidermal differentiation.

    Yira Bermudez

    Full Text Available BACKGROUND: Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells. RESULTS: Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional. CONCLUSIONS: The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s of nicotinic acid receptors in human skin homeostasis.

  11. TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier.

    Jackson, Ben; Brown, Stuart J; Avilion, Ariel A; O'Shaughnessy, Ryan F L; Sully, Katherine; Akinduro, Olufolake; Murphy, Mark; Cleary, Michael L; Byrne, Carolyn


    The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is strong evidence for body-site-dependent dermal programming of epidermal differentiation in which the epidermis responds by altering expression of key barrier proteins, but the underlying mechanisms have not been defined. The LCE multigene cluster encodes barrier proteins that are differentially expressed over the body surface, and perturbation of LCE cluster expression is linked to the common regional skin disease psoriasis. LCE subclusters comprise genes expressed variably in either external barrier-forming epithelia (e.g. skin) or in internal epithelia with less stringent barriers (e.g. tongue). We demonstrate here that a complex of TALE homeobox transcription factors PBX1, PBX2 and Pknox (homologues of Drosophila Extradenticle and Homothorax) preferentially regulate external rather than internal LCE gene expression, competitively binding with SP1 and SP3. Perturbation of TALE protein expression in stratified squamous epithelia in mice produces external but not internal barrier abnormalities. We conclude that epidermal barrier genes, such as the LCE multigene cluster, are regulated by TALE homeodomain transcription factors to produce regional epidermal barriers.

  12. Applied survival analysis using R

    Moore, Dirk F


    Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

  13. Survival Rates for Thymus Cancer

    ... Early Detection, Diagnosis, and Staging Survival Rates for Thymus Cancer Survival rates are often used by doctors ... Ask Your Doctor About Thymus Cancer? More In Thymus Cancer About Thymus Cancer Causes, Risk Factors, and ...

  14. A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

    Han CY


    Full Text Available Cui-yan Han,1,2 Li-ling Yue,2 Ling-yu Tai,1 Li Zhou,2 Xue-yan Li,2 Gui-hua Xing,2 Xing-gang Yang,1 Ming-shuang Sun,1 Wei-san Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Qiqihar Medical University, Qiqihar, People’s Republic of China Abstract: The epidermal growth factor receptor (EGFR serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy. Keywords: EGFR, small peptide, tumor targeting, lung cancer, NLC

  15. Secretion of protein and epidermal growth factor (EGF) by transplanted human pancreas.

    Konturek, J W; Buesing, M; Hopt, U T; Stachura, J; Becker, H D; Konturek, S J


    Epidermal growth factor (EGF) has been localized in human salivary and Brunner's glands and found to stimulate the proliferation of gastrointestinal and pancreatic tissues in animals, but little is known about EGF in human pancreas. This study was designed to determine the distribution and release of EGF in the pancreas and to assess the secretion of EGF and protein by the transplanted human pancreas. The peroxidase antiperoxidase (PAP) immunocytochemical method with anti-hEGF showed that EGF was restricted mainly to the excretory cells lining pancreatic ducts. The EGF immunoreactivity in the pancreatic tissue averaged about 15 +/- 0.5 micrograms/g of tissue wt. The concentration and output of EGF in the pancreatic juice were, respectively, about 3.4 +/- 0.7 ng/mL and 68 + 12 ng/h in basal secretion collected from the whole pancreatic transplant. A significant increase in EGF release from this transplant started about 2 h after its reperfusion and was accompanied by a parallel increase in protein output. Injection of iv secretion (1 U/kg) resulted in a transient rise in EGF output, probably as a result of washout by increased vol flow, whereas HCCK (1 U/kg) caused more prolonged release of EGF accompanied by a marked stimulation of protein secretion. Ingestion of a mixed meal caused an immediate and sustained increment in EGF output, and protein output showed a more protracted increase, reaching its peak in the second postprandial hour. Fractionation of an extract of pancreatic juice on G-5O Sephadex superfine column revealed that EGF immunoreactivity emerged as a major peak in the same position as authentic human EGF (hEGF).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Epidermal growth factor receptor (EGFR-RAS signaling pathway in penile squamous cell carcinoma.

    Hong-Feng Gou

    Full Text Available Penile Squamous Cell Carcinoma (SCC is a rare cancer with poor prognosis and limited response to conventional chemotherapy. The genetic and epigenetic alterations of Epidermal Growth Factor Receptor (EGFR-RAS-RAF signaling in penile SCC are unclear. This study aims to investigate four key members of this pathway in penile SCC. We examined the expression of EGFR and RAS-association domain family 1 A (RASSF1A as well as the mutation status of K-RAS and BRAF in 150 cases of penile SCC. EGFR and RASSF1A expression was evaluated by immunohistochemistry. KRAS mutations at codons 12 and 13, and the BRAF mutation at codon 600 were analyzed on DNA isolated from formalin fixed paraffin embedded tissues by direct genomic sequencing. EGFR expression was positive in all specimens, and its over-expression rate was 92%. RASSF1A expression rate was only 3.42%. Significant correlation was not found between the expression of EGFR or RASSF1A and tumor grade, pT stage or lymph node metastases. The detection of KRAS and BRAF mutations analysis was performed in 94 and 83 tumor tissues, respectively. We found KRAS mutation in only one sample and found no BRAF V600E point mutation. In summary, we found over-expression of EGFR in the majority cases of penile SCC, but only rare expression of RASSF1A, rare KRAS mutation, and no BRAF mutation in penile SCC. These data suggest that anti-EGFR agents may be potentially considered as therapeutic options in penile SCC.

  17. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Pangburn Heather A


    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  18. Structural Characterization and Statistical-Mechanical Model of Epidermal Patterns.

    Chen, Duyu; Aw, Wen Yih; Devenport, Danelle; Torquato, Salvatore


    In proliferating epithelia of mammalian skin, cells of irregular polygon-like shapes pack into complex, nearly flat two-dimensional structures that are pliable to deformations. In this work, we employ various sensitive correlation functions to quantitatively characterize structural features of evolving packings of epithelial cells across length scales in mouse skin. We find that the pair statistics in direct space (correlation function) and Fourier space (structure factor) of the cell centroids in the early stages of embryonic development show structural directional dependence (statistical anisotropy), which is a reflection of the fact that cells are stretched, which promotes uniaxial growth along the epithelial plane. In the late stages, the patterns tend toward statistically isotropic states, as cells attain global polarization and epidermal growth shifts to produce the skin's outer stratified layers. We construct a minimalist four-component statistical-mechanical model involving effective isotropic pair interactions consisting of hard-core repulsion and extra short-range soft-core repulsion beyond the hard core, whose length scale is roughly the same as the hard core. The model parameters are optimized to match the sample pair statistics in both direct and Fourier spaces. By doing this, the parameters are biologically constrained. In contrast with many vertex-based models, our statistical-mechanical model does not explicitly incorporate information about the cell shapes and interfacial energy between cells; nonetheless, our model predicts essentially the same polygonal shape distribution and size disparity of cells found in experiments, as measured by Voronoi statistics. Moreover, our simulated equilibrium liquid-like configurations are able to match other nontrivial unconstrained statistics, which is a testament to the power and novelty of the model. The array of structural descriptors that we deploy enable us to distinguish between normal, mechanically

  19. Survival analysis of aging aircraft

    Benavides, Samuel

    This study pushes systems engineering of aging aircraft beyond the boundaries of empirical and deterministic modeling by making a sharp break with the traditional laboratory-derived corrosion prediction algorithms that have shrouded real-world failures of aircraft structure. At the heart of this problem is the aeronautical industry's inability to be forthcoming in an accurate model that predicts corrosion failures in aircraft in spite of advances in corrosion algorithms or improvements in simulation and modeling. The struggle to develop accurate corrosion probabilistic models stems from a multitude of real-world interacting variables that synergistically influence corrosion in convoluted and complex ways. This dissertation, in essence, offers a statistical framework for the analysis of structural airframe corrosion failure by utilizing real-world data while considering the effects of interacting corrosion variables. This study injects realism into corrosion failures of aging aircraft systems by accomplishing four major goals related to the conceptual and methodological framework of corrosion modeling. First, this work connects corrosion modeling from the traditional, laboratory derived algorithms to corrosion failures in actual operating aircraft. This work augments physics-based modeling by examining the many confounding and interacting variables, such as environmental, geographical and operational, that impact failure of airframe structure. Examined through the lens of censored failure data from aircraft flying in a maritime environment, this study enhances the understanding between the triad of the theoretical, laboratory and real-world corrosion. Secondly, this study explores the importation and successful application of an advanced biomedical statistical tool---survival analysis---to model censored corrosion failure data. This well-grounded statistical methodology is inverted from a methodology that analyzes survival to one that examines failures. Third, this

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

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


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

  1. Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

    Yu-Mu Chen

    Full Text Available Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKIs, although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs and proton pump inhibitors (PPIs as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.Fifty-seven patients (57/269, 21.2% were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234. However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002. Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041. Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

  2. Evaluation Model of System Survivability

    LIU Yuling; PAN Shiying; TIAN Junfeng


    This paper puts forward a survivability evaluation model, SQEM(Survivability Quantitative Evaluation Model), based on lucubrating the main method existed. Then it defines the measurement factors and parses the survivability mathematically, introduces state change probability and the idea of setting the weights of survivability factors dynamically into the evaluating process of SQEM, which improved the accuracy of evaluation. An example is presented to illustrate the way SQEM works, which demonstrated the validity and feasibility of the method.

  3. Nuclear War Survival Skills

    Kearny, C.H.


    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  4. Surviving relatives after suicide

    Nørrelykke, Helle; Cohrt, Pernille


    We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...... suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...

  5. Design of survivable networks

    Stoer, Mechthild


    The problem of designing a cost-efficient network that survives the failure of one or more nodes or edges of the network is critical to modern telecommunications engineering. The method developed in this book is designed to solve such problems to optimality. In particular, a cutting plane approach is described, based on polyhedral combinatorics, that is ableto solve real-world problems of this type in short computation time. These results are of interest for practitioners in the area of communication network design. The book is addressed especially to the combinatorial optimization community, but also to those who want to learn polyhedral methods. In addition, interesting new research problemsare formulated.

  6. Survival after blood transfusion

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus


    the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... as well as for cost-benefit estimation of new blood safety interventions....

  7. Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer.

    Tiseo, Marcello; Capelletti, Marzia; De Palma, Giuseppe; Franciosi, Vittorio; Cavazzoni, Andrea; Mozzoni, Paola; Alfieri, Roberta R; Goldoni, Matteo; Galetti, Maricla; Bortesi, Beatrice; Bozzetti, Cecilia; Loprevite, Maura; Boni, Luca; Camisa, Roberta; Rindi, Guido; Petronini, Pier Giorgio; Ardizzoni, Andrea


    Epidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC). Blood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene copy number and immunohistochemistry expression were determined. Moreover, a panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was also studied. EGFR intron 1 polymorphism showed a statistically significant correlation with the gefitinib response (response rate 25 versus 0%, for patients with a (CA)16 and with a (CA)else genotype, respectively; p = 0.044). Patients with a (CA)16 genotype had a longer survival compared with those with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In addition, cell lines lacking the (CA)16 allele showed a statistically significant higher IC50 compared with cell lines bearing at least one (CA)16 allele (p = 0.003). This study supports a potential role of EGFR intron 1 polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC.

  8. Involvement of aquaporin-3 in epidermal growth factor receptor signaling via hydrogen peroxide transport in cancer cells.

    Hara-Chikuma, Mariko; Watanabe, Sachiko; Satooka, Hiroki


    Aquaporin 3 (AQP3), a water/glycerol channel protein, is capable of transporting hydrogen peroxide (H2O2). Here, we show that AQP3-mediated intracellular H2O2 is involved in epidermal growth factor (EGF)-induced cell signaling and its dependent cell function in the EGF receptor (EGFR)-positive cancer cell lines A431 and H1666. AQP3 knockdown suppressed the transport into the cells of extracellular H2O2 produced in response to EGF in A431 and H1666 cells. EGF-induced Erk and Akt activation, which occurred through SHP2 and/or PTEN modulation, was impaired by AQP3 knockdown. Cell growth and migration induced by EGF stimulation were attenuated in AQP3 knockdown cells compared with those in control cells. Coincidentally, tumor growth of A431 cell xenografts in immunodeficient mice was decreased by AQP3 knockdown. Accordingly, a xenograft with AQP3 knockdown A431 cells significantly enhanced the survival of recipient mice compared with the transplantation with control cells. In addition, AQP3 associated with EGFR and NADPH oxidase 2, which we propose is linked to AQP3 producing a localized increase in intracellular H2O2 to function as a second messenger during EGFR cell signaling. Therefore, our findings suggest that AQP3 is required for EGF-EGFR cell signaling in cancer cells and is a therapeutic target for cancer progression.

  9. Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M

    Shigeru Kawabata


    Full Text Available Lung cancer in never-smokers is an important disease often characterized by mutations in epidermal growth factor receptor (EGFR, yet risk reduction measures and effective chemopreventive strategies have not been established. We identify mammalian target of rapamycin (mTOR as potentially valuable target for EGFR mutant lung cancer. mTOR is activated in human lung cancers with EGFR mutations, and this increases with acquisition of T790M mutation. In a mouse model of EGFR mutant lung cancer, mTOR activation is an early event. As a single agent, the mTOR inhibitor rapamycin prevents tumor development, prolongs overall survival, and improves outcomes after treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI. These studies support clinical testing of mTOR inhibitors in order to prevent the development and progression of EGFR mutant lung cancers.

  10. Differential gene expression in individual papilla-resistant and powdery mildew-infected barley epidermal cells

    Gjetting, T.; Carver, Timothy L. W.; Skøt, Leif


    Resistance and susceptibility in barley to the powdery mildew fungus (Blumeria graminis f. sp. hordei) is determined at the single-cell level. Even in genetically compatible interactions, attacked plant epidermal cells defend themselves against attempted fungal penetration by localized responses...... leading to papilla deposition and reinforcement of their cell wall. This conveys a race-nonspecific form of resistance. However, this defense is not complete, and a proportion of penetration attempts succeed in infection. The resultant mixture of infected and uninfected leaf cells makes it impossible...... to relate powdery mildew-induced gene expression in whole leaves or even dissected epidermal tissues to resistance or susceptibility. A method for generating transcript profiles from individual barley epidermal cells was established and proven useful for analyzing resistant and successfully infected cells...

  11. Antimicrobial susceptibility of Staphylococcus hyicus Isolated from exudative epidermitis in pigs

    Wegener, Henrik Caspar; Watts, J.L.; Salmon, S.A.


    Exudative epidermitis or greasy pig syndrome is caused by the coagulase-variable staphylococcal species Staphylococcus hyicus. Treatment of this disease is problematic because of the limited number of antimicrobial agents available for this purpose. Thirteen antimicrobial agents were evaluated...... for their activities against 100 S. hyicus strains isolated from pigs with exudative epidermitis. Novobiocin was the most active compound tested, with an MIC for 90% of the strains tested (MIC(90)) of less than or equal to 0.06 mu g/ml. Enrofloxacin, ampicillin, and ceftiofur were the next most active compounds...... at ratios of 1:2 (lincomycin to spectinomycin) and 1:8 were more active, with MIC(90)s of 16.0 and 4.0 mu g/ml, respectively. These results indicate that novobiocin and sulfadiazine-trimethoprim were the most active compounds tested against the S. hyicus strains isolated from pigs with exudative epidermitis...

  12. Linear verrucous epidermal nevi-effects of carbon dioxide laser therapy.

    Borzecki, Adam; Strus-Rosińska, Beata; Raszewska-Famielec, Magdalena; Sajdak-Wojtaluk, Agnieszka; Pilat, Pawel


    Linear epidermal nevus is a congenital malformation characterized by linear, often one-sided arrangement. The lesions are localized along the Blaschko's lines, are present at birth, or appear in early childhood. They can be single or multiple, and have various colors-from skin color to dark brown. These lesions persist through the whole life making a significant cosmetic defect. Here, we present three clinical cases of epidermal nevus treated with CO2 laser. In a female patient, verrucous, dark brown skin eruptions were observed at the back of earlobe and down the neck. In the cases of the male patients, the lesions were located in the area of the neck and left blade. The removal of nevi was performed in stages, by cutting and evaporation using a CO2 laser. A very good therapeutic effect was obtained. CO2 laser treatment is the method of choice for the removal of extensive epidermal nevi. It is characterized by high efficacy and safety.

  13. A Taxonomic Study of some Species in Cassiinae (Leguminosae using Leaf Epidermal Characters

    Sefiu Adekilekun SAHEED


    Full Text Available Foliar epidermal characters of ten species from the genus Cassia L. Emend. Gaertner, Senna Miller and Chamaecrista Moench found in South Western Nigeria were studied. The aim was to establish some useful diagnostic features that may be employed in combination with other characters as intra or inter-specific or generic tools for their delimitation. Our results revealed exciting features that are helpful in the identification of each species. These include guard cell area, stomatal index and frequency, presence or absence of trichomes, types of trichomes, as well as their length on epidermal surfaces and wall types. These results, therefore suggest diagnostic features that were found on the epidermal surface that can be employed to justify the separation of the new genera Senna and Chamaecrista from their initial genus Cassia.

  14. Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

    Gruber, Robert; Elias, Peter M; Crumrine, Debra; Lin, Tzu-Kai; Brandner, Johanna M; Hachem, Jean-Pierre; Presland, Richard B; Fleckman, Philip; Janecke, Andreas R; Sandilands, Aileen; McLean, W H Irwin; Fritsch, Peter O; Mildner, Michael; Tschachler, Erwin; Schmuth, Matthias


    Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix. These results clarify how FLG mutations impair epidermal permeability barrier function.

  15. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis.

    Dina Khalaf


    Full Text Available Primary illness with cytomegalovirus leads to latent infection with possible reactivations especially in the immunocompromised patients. Toxic epidermal necrolysis is an immune mediated cytotoxic reaction. A fifty years old female diabetic hypertensive patient with end stage renal disease was admitted with fever of unknown origin, constitutional symptoms, vague upper gastrointestinal symptoms and skin rash. Upper gastrointestinal endoscopic biopsy confirmed her diagnosis with cytomegalovirus esophagitis and duodenitis. Cytomegalovirus immunoglobulin M and immunoglobulin G levels were negative but polymerase chain reaction showed fulminant viremia. Biopsy of the skin rash was consistent with toxic epidermal necrolysis. Despite treatment with Ganciclovir, intravenous immunoglobulins, and granulocyte colony stimulating factor the patient’s condition rapidly deteriorated and she died due to multiorgan failure, disseminated intravascular coagulopathy and overwhelming sepsis. Probably there is a true association linking toxic epidermal necrolysis to fulminant reactivation of cytomegalovirus. The aim of this anecdote is reporting a newly recognized presentation of cytomegalovirus.

  16. Ultrathin epidermal strain sensor based on an elastomer nanosheet with an inkjet-printed conductive polymer

    Tetsu, Yuma; Yamagishi, Kento; Kato, Akira; Matsumoto, Yuya; Tsukune, Mariko; Kobayashi, Yo; Fujie, Masakatsu G.; Takeoka, Shinji; Fujie, Toshinori


    To minimize the interference that skin-contact strain sensors cause natural skin deformation, physical conformability to the epidermal structure is critical. Here, we developed an ultrathin strain sensor made from poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) inkjet-printed on a polystyrene-polybutadiene-polystyrene (SBS) nanosheet. The sensor, whose total thickness and gauge factor were ˜1 µm and 0.73 ± 0.10, respectively, deeply conformed to the epidermal structure and successfully detected the small skin strain (˜2%) while interfering minimally with the natural deformation of the skin. Such an epidermal strain sensor will open a new avenue for precisely detecting the motion of human skin and artificial soft-robotic skin.

  17. The repair of impaired epidermal barrier function in rats by the cutaneous application of linoleic acid.

    Prottey, C; Hartop, P J; Black, J G; McCormack, J I


    Epidermal barrier function in rats was experimentally impaired by two separate means, namely, by rendering the animals deficient in essential fatty acids and by evoking a primary cutaneous irritant response by treating with a solution of sodium laurate. Impaired barrier function was manifested by a greatly increased rate of transepidermal water loss. Application to the skin of sunflower seed oil, which is rich in linoleic acid, rapidly restored to normal the abnormally high rates of transepidermal water loss in both experimental cases, and it was shown with the essential fatty acid-deficient rats that there was a concomitant incorporation of linoleic acid of the sunflower seed oil into epidermal lipids. Cutaneous application of olive oil, which is low in linoleic acid but rich in the non-essential oleic acid, did not influence epidermal barrier function. A close relationship of barrier function and essential fatty acids is indicated.

  18. Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor.

    Konturek, S J; Brzozowski, T; Piastucki, I; Dembinski, A; Radecki, T; Dembinska-Kiec, A; Zmuda, A; Gregory, H


    This study compares the effect of epidermal growth factor and prostaglandins (PGE2 or PGI2), applied topically to gastric mucosa, on gastric secretion and formation of ASA-induced gastric ulcerations in rats. Epidermal growth factor given topically in non-antisecretory doses prevented dose-dependently the formation of ASA-induced ulcers without affecting prostaglandin generation but with a significant rise in DNA synthesis in the oxyntic mucosa. The anti-ulcer effect of topical prostaglandins was also accompanied by an increase in DNA synthesis. This study indicates that topical epidermal growth factor, like PGE2 or PGI2, is cytoprotective and that this cytoprotection is not mediated by the inhibition of gastric secretion or prostaglandin formation but related to the increase in DNA synthesis in oxyntic mucosa. PMID:7030877

  19. Fatal Metastatic Cutaneous Squamous Cell Carcinoma Evolving from a Localized Verrucous Epidermal Nevus

    Hassan Riad


    Full Text Available A malignant transformation is known to occur in many nevi such as a sebaceous nevus or a basal cell nevus, but a verrucous epidermal nevus has only rarely been associated with neoplastic changes. Keratoacanthoma, multifocal papillary apocrine adenoma, multiple malignant eccrine poroma, basal cell carcinoma and cutaneous squamous cell carcinoma (CSCC have all been reported to develop from a verrucous epidermal nevus. CSCC has also been reported to arise from other nevoid lesions like a nevus comedonicus, porokeratosis, a sebaceous nevus, an oral sponge nevus and an ichthyosiform nevus with CHILD syndrome. Here we report a case of progressive poorly differentiated CSCC arising from a localized verrucous epidermal nevus, which caused both spinal cord and brain metastasis.

  20. Giant epidermal inclusion cyst in the male breast: A case report

    KIm, Hyun Jin; Park, Woon Ju; KIm, Sang Wook; Paik, So Ya [Daejin Medical Center Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)


    Giant epidermal inclusion cyst is a rare disease entity, and the occurrence of this cyst in the male breast is extremely rare. We report a case of giant epidermal inclusion cyst in the breast, which presented as a palpable and painful right breast mass in a 63-year-old man. The sonographic and computed tomography (CT) features are described in-depth. Physical examination revealed a firm, well-defined mass in the upper central portion of the right breast. Ultrasonography showed a 5.2 cm sized, oval, circumscribed, and complex cystic and solid mass with posterior acoustic enhancement, and CT showed a well-defined homogeneous low density mass without enhancement in the right breast. Surgical excision was performed, and pathological examination revealed a giant epidermal inclusion cyst.

  1. In situ localization of epidermal stem cells using a novel multi epitope ligand cartography approach.

    Ruetze, Martin; Gallinat, Stefan; Wenck, Horst; Deppert, Wolfgang; Knott, Anja


    Precise knowledge of the frequency and localization of epidermal stem cells within skin tissue would further our understanding of their role in maintaining skin homeostasis. As a novel approach we used the recently developed method of multi epitope ligand cartography, applying a set of described putative epidermal stem cell markers. Bioinformatic evaluation of the data led to the identification of several discrete basal keratinocyte populations, but none of them displayed the complete stem cell marker set. The distribution of the keratinocyte populations within the tissue was remarkably heterogeneous, but determination of distance relationships revealed a population of quiescent cells highly expressing p63 and the integrins alpha(6)/beta(1) that represent origins of a gradual differentiation lineage. This population comprises about 6% of all basal cells, shows a scattered distribution pattern and could also be found in keratinocyte holoclone colonies. The data suggest that this population identifies interfollicular epidermal stem cells.

  2. Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

    Dvorak, J.; Sirak, I.; Petera, J. [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Oncology and Radiotherapy; Sitorova, V.; Ryska, A.; Hatlova, J. [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Pathology; Richter, I. [Regional Hospital Liberec, Liberec (Czech Republic); Charles Univ. Medical School, Hradec Kralove (Czech Republic); Ferko, A. [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Surgery; Melichar, B. [Palacky Univ. Medical School and Teaching Hospital, Olomouc (Czech Republic). Dept. of Oncology


    Purpose: The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma. Patients and methods: A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Results: Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis. Conclusion: An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied. (orig.)

  3. Delivery of epidermal neural crest stem cells (EPI-NCSC) to hippocamp in Alzheimer's disease rat model.

    Esmaeilzade, Banafshe; Nobakht, Maliheh; Joghataei, Mohammad Taghi; Rahbar Roshandel, Nahid; Rasouli, Homa; Samadi Kuchaksaraei, Ali; Hosseini, Seyed Mohammad; Najafzade, Nowruz; Asalgoo, Sara; Hejazian, Leila Beygom; Moghani Ghoroghi, Fatima


    Alzheimer's disease (AD) is characterized by progressive neuronal loss in hippocamp. Epidermal neural crest stem cells (EPI-NCSC) can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the effects of transplanting EPI-NCSC into AD rat model. Two weeks after induction of AD by injection of Amyloid-β1-40 into CA1 area of rat hippocamp, Y-maze and single-trial passive avoidance tests were used to show deficit of learning and memory abilities. EPI-NCSC were obtained from the vibrissa hair follicle of rat, cultured and labeled with bromodeoxyuridine. When Alzheimer was proved by behavioral tests, EPI-NCSC was transplanted into CA3 area of hippocamp in AD rat model. The staining of EPI-NCSC markers (nestin and SOX10) was done in vitro. Double-labeling immunofluorescence was performed to study survival and differentiation of the grafted cells. We showed that transplanted EPI-NCSC survive and produce many neurons and a few glial cells, presenting glial fibrillary acidic protein. Total number of granule cells in hippocamp was estimated to be more in the AD rat model with transplanted cells as compared to AD control group. We observed that rats with hippocampal damage made more errors than control rats on the Y-maze, when reward locations were reversed. Transplanted cells were migrated to all areas of hippocamp and the total number of granule cell in treatment group was equal compared to control group. Transplantation of EPI-NCSC into hippocamp might differentiate into cholinergic neurons and could cure impairment of memory in AD rat model.

  4. Synthetic Lethality Screen Identifies RPS6KA2 as Modifier of Epidermal Growth Factor Receptor Activity in Pancreatic Cancer

    Nada Milosevic


    Full Text Available Pancreatic cancer is characterized by a high degree of resistance to chemotherapy. Epidermal growth factor receptor (EGFR inhibition using the small-molecule inhibitor erlotinib was shown to provide a small survival benefit in a subgroup of patients. To identify kinases whose inhibition acts synergistically with erlotinib, we employed a kinome-wide small-interfering RNA (siRNA-based loss-of-function screen in the presence of erlotinib. Of 779 tested kinases, we identified several targets whose inhibition acted synergistically lethal with EGFR inhibition by erlotinib, among them the S6 kinase ribosomal protein S6 kinase 2 (RPS6KA2/ribosomal S6 kinase 3. Activated RPS6KA2 was expressed in approximately 40% of 123 human pancreatic cancer tissues. RPS6KA2 was shown to act downstream of EGFR/RAS/mitogen-activated protein kinase kinase (MEK/extracellular-signal regulated kinase (ERK signaling and was activated by EGF independently of the presence of KRAS mutations. Knockdown of RPS6KA2 by siRNA led to increased apoptosis only in the presence of erlotinib, whereas RPS6KA2 activation or overexpression rescued from erlotinib- and gemcitabine-induced apoptosis. This effect was at least in part mediated by downstream activation of ribosomal protein S6. Genetic as well as pharmacological inhibition of RPS6KA2 by the inhibitor BI-D1870 acted synergistically with erlotinib. By applying this synergistic lethality screen using a kinome-wide RNA interference-library approach, we identified RPS6KA2 as potential drug target whose inhibition synergistically enhanced the effect of erlotinib on tumor cell survival. This kinase therefore represents a promising drug candidate suitable for the development of novel inhibitors for pancreatic cancer therapy.

  5. Clinical, microscopic and microbial characterization of exfoliative superficial pyoderma-associated epidermal collarettes in dogs.

    Banovic, Frane; Linder, Keith; Olivry, Thierry


    The microscopic and microbial features of the spreading epidermal collarettes of canine exfoliative superficial pyodermas are poorly characterized. To characterize the clinical, cytological, microbial and histopathological features of epidermal collarettes in five dogs. Cytology from the margins of collarettes identified neutrophils, extracellular and intracellular cocci within neutrophils but no acantholytic keratinocytes. Phenotypic and genotypic analyses identified all bacterial isolates from the centre and margin of five epidermal collarettes as Staphylococcus pseudintermedius. PCRs of collarette-associated Staphylococcus strains did not amplify genes encoding for the known exfoliative toxins expA and expB, whereas the predicted siet and speta amplification products were detected in all isolates. Microscopically, epidermal collarettes consisted of interfollicular, epidermal spongiotic pustules. Advancing edges of lesions consisted of peripheral intracorneal clefts in the deep stratum disjunctum above an intact stratum compactum; they contained lytic neutrophil debris, bacterial cocci and fluid, but no acantholytic keratinocytes. This intracorneal location of bacteria was confirmed using Gram stains and fluorescent in situ hybridization with eubacterial- and Staphylococcus-specific probes. The indirect immunofluorescence staining patterns of desmoglein-1, desmocollin-1, claudin-1, E-cadherin and corneodesmosin were discontinuous and patchy in areas of spongiotic pustules, whereas only that of corneodesmosin was weaker and patchy in advancing collarette edges. Epidermal collarettes represent unique clinical and histological lesions of exfoliative superficial pyodermas that are distinct from those of impetigo and superficial bacterial folliculitis. The characterization of possible causative staphylococcal exfoliatin proteases and the role of corneodesmosin in collarette pathogenesis deserve further investigation. © 2016 ESVD and ACVD.

  6. Phytochemical and anti-bacterial activity of epidermal glands extract of Christella parasitica (L.) H. Lev.

    Paul Raj K; Irudayaraj V; Johnson M; Patric Raja D


    Objective: To study the morphology, biochemistry and bioactivity of the epidermal glands of the glandular morphotype of Christella parasitica (C. parasitica) (L.) H. Lev. Methods:Morphological studies on epidermal glands were carried out by using light microscope and scanning electron microscope. To prepare the extract, the shade-dried fronds of glandular morphotype were soaked in acetone. For antibacterial studies paper disc method was followed by using various pathogenic bacteria. Results: Detailed micromorphological, phytochemical and bioactivity studies on a medicinal fern C. parasitica (L.) H. Lev. showed its intraspecific variation in antibacterial activity. The presence or absence of the epidermal glands was the key factor for antibacterial activity in the morphovariants of this species. The epidermal glands were orange-coloured, stalked and elongated ones of about 84.2 μm 45 μm, and distributed on the undersurface of costa, costules and veins in croziers, young and mature leaves. Frequency of glands varied from 15/cm on costa in mature leaves to 140/cm on costules in croziers. The acetone extract of the glands showed antibacterial activities and also toxic effect against mosquito larvae and tadpoles of frog. Preliminary phytochemical analysis and HPLC studies of the gland extract showed the presence of various kinds of terpenoids, alkaloids, tannins, saponins and flavonoids in it. Conclusions: The present study shows that epidermal glands of the glandular morphotype of C. parasitica (L.) H. Lev. have several bioactive compounds and such rare morphovariant should be conserved in nature. The next step is to isolate the pure compounds and to screen the bioactivity of individual compounds of the epidermal glands.

  7. Phytochemical and anti-bacterial activity of epidermal glands extract of Christella parasitica (L.) H. Lev.

    Paul; Raj; K; Irudayaraj; V; Johnson; M; Patric; Raja; D


    Objective:To study the morphology,biochemistry and bioactivity of the epidermal glands of the glandular morphotype of Christella parasitica(C.parasitica)(L.) H.Lev.Methods: Morphological studies on epidermal glands were earned out by using light microscope and scanning electron microscope.To prepare the extract,the shade-dried fronds of glandular morphotype were soaked in acetone.For antibacterial studies paper disc method was followed by using various pathogenic bacteria.Results:Detailed micromorphological,phytochemical and bioactivity studies on a medicinal fern C.parasitica(L.) H.Lev.showed its inlraspecific variation in antibacterial activity.The presence or absence of the epidermal glands was the key factor for antibacterial activity in the morphovariants of this species.The epidermal glands were orange-coloured,stalked and elongated ones of about 84.2μm×45μm,and distributed on the undersurface of cosla,coslules and veins in croziers,young and mature leaves.Frequency of glands varied from 15/cm on costa in mature leaves to 140/cm on costules in croziers.The acetone extract of the glands showed antibacterial activities and also toxic effect against mosquito larvae and tadpoles of frog.Preliminary phytochemical analysis and HPLC studies of the gland extract showed the presence of various kinds of terpenoids,alkaloids,tannins,saponins and flavonoids in it.Conclusions:The present study shows that epidermal glands of the glandular morphotype of C. parasitica(L.) H.Lev.have several bioactive compounds and such rare moiphovariant should be conserved in nature.The next step is to isolate the pure compounds and to screen the bioactivity of individual compounds of the epidermal glands.

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

    Srinivas, L.; Colburn, N.H.


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

  9. Epidermal growth factor enemas for induction of remission in left-sided ulcerative colitis

    Hugo Nodarse-Cuní


    Full Text Available Introduction: ulcerative colitis is a little known chronic inflammatory disease in colonic mucosa. The positive effect of epidermal growth factor was shown in a previous report, with enema use for treatment of mild to moderate left-sided manifestation of the disease. This evidence provided the basis for evaluating the efficacy and safety profile of a viscous solution of this product. Methods: thirty-one patients were randomized to three groups for daily medications during 14 days. Twelve received one 10 mg enema of epidermal growth factor dissolved in 100 mL of viscous solution whereas nine were treated with placebo enema; both groups also received 1.2 g of oral mesalamine per day. The other group included ten patients with 3 g / 100 mL of mesalamine enema. Primary end point was clinical responses after two weeks of treatment, defined as a decreased of, at least three points from baseline, the Disease Activity Index and endoscopic or histological evidences of improvement. Results: remission of disease was observed in all patients in the epidermal growth factor group, and six in both, mesalamine enema and placebo group. All the comparisons between groups showed statistically significant superiority for epidermal growth factor, the only product with significant reduction in disease activity index as well as the presence and intensity of digestive symptoms in patients after treatment. None adverse event was reported. Conclusions: the results agree with previous molecular and clinical evidences, indicating that the epidermal growth factor is effective to reduce disease activity and to induce remission. A new study involving more patients should be conducted to confirm the efficacy of the epidermal growth factor enemas.

  10. Simple preparation of plant epidermal tissue for laser microdissection and downstream quantitative proteome and carbohydrate analysis.

    Falter, Christian; Ellinger, Dorothea; von Hülsen, Behrend; Heim, René; Voigt, Christian A


    The outwardly directed cell wall and associated plasma membrane of epidermal cells represent the first layers of plant defense against intruding pathogens. Cell wall modifications and the formation of defense structures at sites of attempted pathogen penetration are decisive for plant defense. A precise isolation of these stress-induced structures would allow a specific analysis of regulatory mechanism and cell wall adaption. However, methods for large-scale epidermal tissue preparation from the model plant Arabidopsis thaliana, which would allow proteome and cell wall analysis of complete, laser-microdissected epidermal defense structures, have not been provided. We developed the adhesive tape - liquid cover glass technique (ACT) for simple leaf epidermis preparation from A. thaliana, which is also applicable on grass leaves. This method is compatible with subsequent staining techniques to visualize stress-related cell wall structures, which were precisely isolated from the epidermal tissue layer by laser microdissection (LM) coupled to laser pressure catapulting. We successfully demonstrated that these specific epidermal tissue samples could be used for quantitative downstream proteome and cell wall analysis. The development of the ACT for simple leaf epidermis preparation and the compatibility to LM and downstream quantitative analysis opens new possibilities in the precise examination of stress- and pathogen-related cell wall structures in epidermal cells. Because the developed tissue processing is also applicable on A. thaliana, well-established, model pathosystems that include the interaction with powdery mildews can be studied to determine principal regulatory mechanisms in plant-microbe interaction with their potential outreach into crop breeding.

  11. Simple preparation of plant epidermal tissue for laser microdissection and downstream quantitative proteome and carbohydrate analysis

    Christian eFalter


    Full Text Available The outwardly directed cell wall and associated plasma membrane of epidermal cells represent the first layers of plant defense against intruding pathogens. Cell wall modifications and the formation of defense structures at sites of attempted pathogen penetration are decisive for plant defense. A precise isolation of these stress-induced structures would allow a specific analysis of regulatory mechanism and cell wall adaption. However, methods for large-scale epidermal tissue preparation from the model plant Arabidopsis thaliana, which would allow proteome and cell wall analysis of complete, laser-microdissected epidermal defense structures, have not been provided. We developed the adhesive tape – liquid cover glass technique for simple leaf epidermis preparation from A. thaliana, which is also applicable on grass leaves. This method is compatible with subsequent staining techniques to visualize stress-related cell wall structures, which were precisely isolated from the epidermal tissue layer by laser microdissection coupled to laser pressure catapulting. We successfully demonstrated that these specific epidermal tissue samples could be used for quantitative downstream proteome and cell wall analysis. The development of the adhesive tape – liquid cover glass technique for simple leaf epidermis preparation and the compatibility to laser microdissection and downstream quantitative analysis opens new possibilities in the precise examination of stress- and pathogen-related cell wall structures in epidermal cells. Because the developed tissue processing is also applicable on A. thaliana, well-established, model pathosystems that include the interaction with powdery mildews can be studied to determine principal regulatory mechanisms in plant-microbe interaction with their potential outreach into crop breeding.

  12. Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona


    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte–associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell–driven disease memory in psoriasis. PMID:24610014

  13. Programmed Cell Death Progresses Differentially in Epidermal and Mesophyll Cells of Lily Petals.

    Hiroko Mochizuki-Kawai

    Full Text Available In the petals of some species of flowers, programmed cell death (PCD begins earlier in mesophyll cells than in epidermal cells. However, PCD progression in each cell type has not been characterized in detail. We separately constructed a time course of biochemical signs and expression patterns of PCD-associated genes in epidermal and mesophyll cells in Lilium cv. Yelloween petals. Before visible signs of senescence could be observed, we found signs of PCD, including DNA degradation and decreased protein content in mesophyll cells only. In these cells, the total proteinase activity increased on the day after anthesis. Within 3 days after anthesis, the protein content decreased by 61.8%, and 22.8% of mesophyll cells was lost. A second peak of proteinase activity was observed on day 6, and the number of mesophyll cells decreased again from days 4 to 7. These biochemical and morphological results suggest that PCD progressed in steps during flower life in the mesophyll cells. PCD began in epidermal cells on day 5, in temporal synchrony with the time course of visible senescence. In the mesophyll cells, the KDEL-tailed cysteine proteinase (LoCYP and S1/P1 nuclease (LoNUC genes were upregulated before petal wilting, earlier than in epidermal cells. In contrast, relative to that in the mesophyll cells, the expression of the SAG12 cysteine proteinase homolog (LoSAG12 drastically increased in epidermal cells in the final stage of senescence. These results suggest that multiple PCD-associated genes differentially contribute to the time lag of PCD progression between epidermal and mesophyll cells of lily petals.

  14. Epidermal hyperplasia induced by Raf-MAPK signaling requires Stat3 activation.

    Tarutani, Masahito; Nakajima, Kimiko; Takaishi, Mikiro; Ohko, Kentaro; Sano, Shigetoshi


    Raf is one of the downstream effectors of Ras GTPases, and plays a key role in regulating cell proliferation and differentiation through the activation of MAPK. We have previously demonstrated that temporal induction of Raf in the epidermis of K14-Raf:ER transgenic mice results in epidermal hyperplasia resembling squamous cell carcinoma and psoriasis. It has been demonstrated that epidermal Stat3 activation is required for psoriasis development, since keratinocyte-specific Stat3 activation in a mouse model elicits a psoriasis-like phenotype, which is reversed by inhibition of Stat3 signaling. The aim of this study was whether Stat3 signaling is involved in Raf-MAPK-dependent epidermal hyperplasia. K14-Raf:ER transgenic mice, in which the 4-hydroxytamoxifen (4OHT)-responsive mutant estrogen receptor ligand binding domain-Raf fusion gene is expressed under control of the keratin 14 promoter, were mated with epidermis-specific Stat3 null mice (K5-Cre.Stat3(flox/flox)). K5-Cre.Stat3(flox/flox) mice were used to define the impact of Stat3 deficiency on Raf-induced epidermal hyperplasia. Over-expression of Raf by 4OHT treatment in K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice greatly attenuated the epidermal hyperplasia and dermal cell infiltrates compared with K14-Raf:ER;K5-Cre.Stat3(flox/WT) mice. Also, up-regulation of psoriasis-associated cytokine profiles, including VEGF, was inhibited in the skin from K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice following 4OHT treatment. These results clearly indicate that Raf-MAPK-dependent psoriatic-like epidermal hyperplasia requires Stat3 signaling in keratinocytes. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Consistency of Random Survival Forests.

    Ishwaran, Hemant; Kogalur, Udaya B


    We prove uniform consistency of Random Survival Forests (RSF), a newly introduced forest ensemble learner for analysis of right-censored survival data. Consistency is proven under general splitting rules, bootstrapping, and random selection of variables-that is, under true implementation of the methodology. Under this setting we show that the forest ensemble survival function converges uniformly to the true population survival function. To prove this result we make one key assumption regarding the feature space: we assume that all variables are factors. Doing so ensures that the feature space has finite cardinality and enables us to exploit counting process theory and the uniform consistency of the Kaplan-Meier survival function.

  16. Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

    Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog


    Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

  17. Nucleolin inhibitor GroA triggers reduction in epidermal growth factor receptor activation: Pharmacological implication for glial scarring after spinal cord injury.

    Goldshmit, Yona; Schokoroy Trangle, Sari; Afergan, Fabian; Iram, Tal; Pinkas-Kramarski, Ronit


    Glial scarring, formed by reactive astrocytes, is one of the major impediments for regeneration after spinal cord injury (SCI). Reactive astrocytes become hypertrophic, proliferate and secrete chondroitin sulphate proteoglycans into the extracellular matrix (ECM). Many studies have demonstrated that epidermal growth factor receptors (EGFR) can mediate astrocyte reactivity after neurotrauma. Previously we showed that there is crosstalk between nucleolin and EGFR that leads to increased EGFR activation followed by increased cell proliferation. Treatment with the nucleolin inhibitor GroA (AS1411) prevented these effects in vitro and in vivo. In this study, we hypothesized that similar interactions may mediate astrogliosis after SCI. Our results demonstrate that nucleolin and EGFR interaction may play a pivotal role in mediating astrocyte proliferation and reactivity after SCI. Moreover, we demonstrate that treatment with GroA reduces EGFR activation, astrocyte proliferation and chondroitin sulphate proteoglycans secretion, therefore promoting axonal regeneration and sprouting into the lesion site. Our results identify, for the first time, a role for the interaction between nucleolin and EGFR in astrocytes after SCI, indicating that nucleolin inhibitor GroA may be used as a novel treatment after neurotrauma. A major barrier for axonal regeneration after spinal cord injury is glial scar created by reactive and proliferating astrocytes. EGFR mediate astrocyte reactivity. We showed that inhibition of nucleolin by GroA, reduces EGFR activation, which results in attenuation of astrocyte reactivity and proliferation in vivo and in vitro. EGFR, epidermal growth factor receptor.

  18. Epidermólise bolhosa: um desafio para a (sobre) vida

    Prazeres, Silvana Mara Janning


    A epidermólise bolhosa (EB) hereditária é uma genodermatose, ou seja, doença de pele transmitida geneticamente. É uma doença rara, a qual se caracteriza pelo aparecimento de bolhas, ulcerações ou feridas em qualquer local da superfície corporal em resposta a mínimos traumas ou desencadeadas espontaneamente. Os objetivos deste estudo foram elaborar uma cartilha para o cuidado, no âmbito hospitalar, de neonato com epidermólise bolhosa. Investigar como os profissionais de saúde que atuam em UTI ...

  19. Human Papilloma Viral DNA Replicates as a Stable Episome in Cultured Epidermal Keratinocytes

    Laporta, Robert F.; Taichman, Lorne B.


    Human papilloma virus (HPV) is poorly understood because systems for its growth in tissue culture have not been developed. We report here that cultured human epidermal keratinocytes could be infected with HPV from plantar warts and that the viral DNA persisted and replicated as a stable episome. There were 50-200 copies of viral DNA per cell and there was no evidence to indicate integration of viral DNA into the cellular genome. There was also no evidence to suggest that viral DNA underwent productive replication. We conclude that cultured human epidermal keratinocytes may be a model for the study of certain aspects of HPV biology.

  20. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI)


    It has been suggested that epidermal Langerhans cells (LC) bearing immunoglobulin E (IgE) may be involved in the genesis of atopic disease. The identity of the IgE receptor(s) on LC remained unclear, although it represents a crucial point in understanding cellular events linked to the binding of allergens to LC via IgE. In this report, we demonstrate that epidermal LC express the high affinity receptor for the Fc fragment of IgE (Fc epsilon RI) which has, so far, only been described on mast c...


    Abayomi Ezekiel FOLORUNSO


    Full Text Available The foliar epidermal studies were carried out on Cymbopogon citratus and Cymbopogon giganteus with the aim of determining the patterns of variation in their epidermal characteristics and assessing their value in species identification and classification. The characters of diagnostic importance in the identification of C. citratus are the micro hairs, which are sparsely distributed in the adaxial epidermis and prickle hairs present in both abaxial and adaxial epidermis. The diagnostic character for C. giganteus is the papillae seen alongside their long cells.

  2. An epidermal inclusion cyst mimicking chronic prepatellar bursitis: a case report.

    Mayo, Meredith; Werner, Jordan; Joshi, Bhavesh; Abramovici, Liugia; Strauss, Eric J


    Soft tissue lesions are common to the prepatellar region, often due to acute or chronic trauma, and most frequently include prepatellar bursitis, lipomas, and ganglion cysts. We report a case of a posttraumatic prepatellar epidermal inclusion cyst to highlight the diagnostic complexities that can arise with soft tissue lesions in this location. On the basis of our case report, treating orthopaedic surgeons should consider the possibility of an epidermal inclusion cyst in patients who present with atypical anterior soft tissue masses with a history of trauma to the anterior knee. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. The "Alarmins" HMBG1 and IL-33 Downregulate Structural Skin Barrier Proteins and Impair Epidermal Growth

    Nygaard, Uffe; van den Bogaard, Ellen H; Niehues, Hanna;


    investigated the impact of HMGB1 and IL-33 on gene transcription, protein expression and epidermal differentiation across 3 distinct keratinocyte in vitro models. Primary keratinocytes from healthy donors were used in submerged monolayer cultures, 3D human epidermis equivalents and 3D human skin equivalents......The epidermal-derived "alarmins" high-mobility group box 1 (HMGB1) protein and interleukin-33 (IL-33) are upregulated in patients with atopic dermatitis. How-ever, their capacity as pro-inflammatory cytokines and their derived effects on skin barrier regulation are poorly elucidated. We...

  4. An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head.

    Mace, Kimberly A; Pearson, Joseph C; McGinnis, William


    We used wounded Drosophila embryos to define an evolutionarily conserved pathway for repairing the epidermal surface barrier. This pathway includes a wound response enhancer from the Ddc gene that requires grainy head (grh) function and binding sites for the Grh transcription factor. At the signaling level, tyrosine kinase and extracellular signal-regulated kinase (ERK) activities are induced in epidermal cells near wounds, and activated ERK is required for a robust wound response. The conservation of this Grh-dependent pathway suggests that the repair of insect cuticle and mammal skin is controlled by an ancient, shared control system for constructing and healing the animal body surface barrier.

  5. Vancomycin-associated linear IgA disease mimicking toxic epidermal necrolysis*

    Pereira, Amanda Regio; de Moura, Luis Henrique Barbizan; Pinheiro, Jhonatan Rafael Siqueira; Pasin, Victor Pavan; Enokihara, Milvia Maria Simões e Silva; Porro, Adriana Maria


    Linear IgA dermatosis is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. In the last three decades, many different drugs have been associated with the drug-induced form of the disease, especially vancomycin. We report a case of vancomycin-induced linear IgA disease mimicking toxic epidermal necrolysis. The aim of this work is to emphasize the need to include this differential diagnosis in cases of epidermal detachment and to review the literature on the subject and this specific clinical presentation. PMID:28300888

  6. Diffuse intestinal submucosal lipomatosis with incidental epidermal inclusion cyst of caecum clinically masquerading as carcinoma caecum.

    Thakur, Brijesh; Kishore, Sanjeev; Bhardwaj, Aparna; Kudesia, Sandip


    Symptomatic diffuse submucosal intestinal lipomatosis is a rare entity. Also few cases of epidermal inclusion cyst of caecum have been reported in literature. Here, we are presenting a rare case of intestinal submucosal lipomatosis with coincidence of epidermal inclusion cyst of caecum and presumptively diagnosed as carcinoma of ileocaecal region during surgery in a 55 years old male. Both are rare entity considering the location even they should be kept as a differential diagnosis in unusual cases of intestinal perforations with inconclusive radiological findings or clinical uncertainity.

  7. Diffuse intestinal submucosal lipomatosis with incidental epidermal inclusion cyst of caecum clinically masquerading as carcinoma caecum

    Brijesh Thakur


    Full Text Available Symptomatic diffuse submucosal intestinal lipomatosis is a rare entity. Also few cases of epidermal inclusion cyst of caecum have been reported in literature. Here, we are presenting a rare case of intestinal submucosal lipomatosis with coincidence of epidermal inclusion cyst of caecum and presumptively diagnosed as carcinoma of ileocaecal region during surgery in a 55 years old male. Both are rare entity considering the location even they should be kept as a differential diagnosis in unusual cases of intestinal perforations with inconclusive radiological findings or clinical uncertainity.

  8. A Case of "Inflammatory Linear Verrucous Epidermal Nevus" (ILVEN) Treated with CO2 Laser Ablation.

    Gianfaldoni, Serena; Tchernev, Georgi; Gianfaldoni, Roberto; Wollina, Uwe; Lotti, Torello


    The "inflammatory linear verrucous epidermal nevus" is a rare disease, consisting of hyperplasia of the normal components of the epidermis. Its clinical features include erythematous and hyperkeratosic, warty, sometimes psoriasiform or lichenoid patches with a typical linear arrangement. At present, there are no effective medical therapies available. Currently, the best therapeutic results are obtained with surgical excision or the latest laser therapy. The Authors present a 9-years old girl with an inflammatory linear verrucous epidermal nevus on her neck, successfully treated with CO2 Laser ablation.

  9. [Effects of transfection of human epidermal growth factor gene with adenovirus vector on biological characteristics of human epidermal cells].

    Yin, Kai; Ma, Li; Shen, Chuan'an; Shang, Yuru; Li, Dawei; Li, Longzhu; Zhao, Dongxu; Cheng, Wenfeng


    To investigate the suitable transfection condition of human epidermal cells (hECs) with human epidermal growth factor (EGF) gene by adenovirus vector (Ad-hEGF) and its effects on the biological characteristics of hECs. hECs were isolated from deprecated human fresh prepuce tissue of circumcision by enzyme digestion method and then sub-cultured. hECs of the third passage were used in the following experiments. (1) Cells were divided into non-transfection group and 5, 20, 50, 100, 150, and 200 fold transfection groups according to the random number table (the same grouping method below), with 3 wells in each group. Cells in non-transfection group were not transfected with Ad-hEGF gene, while cells in the latter six groups were transfected with Ad-hEGF gene in multiplicities of infection (MOI) of 5, 20, 50, 100, 150, and 200 respectively. The morphology of the cells was observed with inverted phase contrast microscope, and expression of green fluorescent protein of the cells was observed with inverted fluorescence microscope at transfection hour (TH) 24, 48, and 72. (2) Another three batches of cells were collected, grouped, and treated as above, respectively. Then the transfection rate of Ad-hEGF gene was detected by flow cytometer (n=3), the mass concentration of EGF in culture supernatant of cells was detected by enzyme-linked immunosorbent assay (n=6), and the proliferation activity of cells was detected by cell counting kit 8 (CCK8) and microplate reader (n=6) at TH 24, 48, and 72, respectively. (3) Cells were collected and divided into non-transfection group and transfection group, with 6 wells in each group. Cells in non-transfection group were cultured with culture supernatant of cells without transfection, while cells in transfection group were cultured with culture supernatant of cells which were transfected with Ad-hEGF gene in the optimum MOI (50). CCK8 and microplate reader were used to measure the biological activity of EGF secreted by cells on culture

  10. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors

    Jin, Sun Hee [Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Choi, Dalwoong [Department of Public Health Science, Korea University, Seoul 136-701 (Korea, Republic of); Chun, Young-Jin [College of Pharmacy, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Noh, Minsoo, E-mail: [Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of)


    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. - Highlights: • Cutaneous inflammatory gene signature consists of PDZK1IP1, IL-24, H19 and filaggrin. • Pro-inflammatory cytokines increase IL-24 production in human keratinocytes. • Environmental toxic stressors increase IL-24 production in human keratinocytes. • IL-24 stimulates human keratinocytes to

  11. Calcium-calmodulin signalling is involved in light-induced acidification by epidermal leaf cells of pea, Pisum sativum L.

    Elzenga, JTM; Staal, M; Prins, HBA


    Pathways of signal transduction of red and blue light-dependent acidification by leaf epidermal cells were studied using epidermal strips of the Argenteum mutant of Pisum sativum. In these preparations the contribution of guard cells to the acidification is minimal. The hydroxypyridine nifedipine, a

  12. Epidermal Patterning Genes Impose Non-cell Autonomous Cell Size Determination and have Additional Roles in Root Meristem Size Control

    Christian L?fke; Kai Dünser; Jürgen Kleine-Vehn


    The regulation of cellular growth is of vital importance for embryonic and postembryonic patterning. Growth regulation in the epidermis has importance for organ growth rates in roots and shoots, proposing epidermal cells as an interesting model for cellular growth regulation. Here we assessed whether the root epidermis is a suitable model system to address cell size determination. In Arabidopsis thaliana L., root epidermal cells are regularly spaced in neighbouring tricho-(root hair) and atrichoblast (non-hair) cells, showing already distinct cell size regulation in the root meristem. We determined cell sizes in the root meristem and at the onset of cellular elongation, revealing that not only division rates but also cellular shape is distinct in tricho-and atrichoblasts. Intriguingly, epidermal-patterning mutants, failing to define differential vacuolization in neighbouring epidermal cell files, also display non-differential growth. Using these epidermal-patterning mutants, we show that polarized growth behaviour of epidermal tricho-and atrichoblast is interdependent, suggesting non-cell autonomous signals to integrate tissue expansion. Besides the interweaved cell-type-dependent growth mechanism, we reveal an additional role for epidermal patterning genes in root meristem size and organ growth regulation. We conclude that epidermal cells represent a suitable model system to study cell size determination and interdependent tissue growth.

  13. AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning

    Yunbo Qiao; Yue Zhu; Nengyin Sheng; Jun Chen; Ran Tao; Qingqing Zhu; Ting Zhang; Cheng Qian; Naihe Jing


    Bone morphogenetic protein (BMP) inhibits neural specification and induces epidermal differentiation during ectodermal patterning.However,the mechanism of this process is not well understood.Here we show that AP2γ,a transcription factor activator protein (AP)-2 family member,is upregulated by BMP4 during neural differentiation of pluripotent stem cells.Knockdown of AP2γ facilitates mouse embryonic stem cell (ESC) neural fate determination and impairs epidermal differentiation,whereas AP2γ overexpression inhibits neural conversion and promotes epidermal commitment.In the early chick embryo,AP2γ is expressed in the entire epiblast before HH stage 3 and gradually shifts to the putative epidermal ectoderm during HH stage 4.In the future neural plate AP2γ inhibits excessive neural expansion and it also promotes epidermal development in the surface ectoderm.Moreover,AP2γ knockdown in ESCs and chick embryos partially rescued the neural inhibition and epidermal induction effects of BMP4.Mechanistic studies showed that BMP4 directly regulates AP2γ expression through Smad1 binding to the AP2γ promoter.Taken together,we propose that during the early stages of ectodermal patterning in the chick embryo,AP2γ acts downstream of the BMP pathway to restrict precocious neural expansion in the prospective neural plate and initiates epidermal differentiation in the future epidermal ectoderm.

  14. Bacteriological examination of inflamed epidermal cysts: a survey between 2008 and 2009 at a hospital in southern Taiwan

    Yen-Hsi Liu


    Conclusions: Both aerobic and anaerobic microorganisms were present in the inflamed epidermal cysts, although the anaerobic bacteria, specifically, Propionibacterium spp and Peptostreptococcus spp, were isolated slightly more frequently. Antibiotics directed against anaerobes may be considered in the treatment regimen for inflamed epidermal cysts.


    Parekh, Niyati; Chandran, Urmila; Bandera, Elisa V.


    Although obesity is a well known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colorectal cancer. We note that the evidence over-represents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors. PMID:22540252

  16. Surviving Sepsis Campaign

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed


    , and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low......, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations......, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects...

  17. Use of a serum-free epidermal culture model to show deleterious effects of epidermal growth factor on morphogenesis and differentiation.

    Chen, C S; Lavker, R M; Rodeck, U; Risse, B; Jensen, P J


    The presence of serum has limited the utility of many culture models for the study of cytokine effects because its complexity and variability can confound the interpretation of data. In the present study, a serum-free skin co-culture model was used to investigate the effect of exogenous epidermal growth factor (EGF) on epidermal proliferation and differentiation. Human keratinocytes cultured on collagen rafts at the air-liquid interface produced a well-differentiated epithelium that resembled normal epidermis. Keratin filaments, membrane-coating granules, and keratohyalin granules were all observed. Epidermal differentiation markers keratin K1/K10, involucrin, and transglutaminase were localized in most of the suprabasal layers, whereas profilaggrin/filaggrin was confined to the granular layers and stratum corneum. In the continual presence of 10-20 ng/mL EGF, the epidermis was less organized, thinner, and less proliferative. EGF also depressed several indicators of differentiation: The number of keratohyalin granules and membrane-coating granules was greatly decreased; antigen expression of profilaggrin/filaggrin appeared diminished by immunocytochemical staining; frequent nuclear retention was noted in the relatively thickened stratum corneum-like layers. As detected by immunohistochemical staining, the expression of EGF receptor in the epidermis was reduced by exogenous EGF. These data illustrate that EGF cannot be considered a simple mitogen. Our findings also underscore the importance of using sophisticated culture models to assess complex cytokine effects that may be dependent on the architecture of a differentiating epidermis.

  18. Real-time three-dimensional imaging of epidermal splitting and removal by high-definition optical coherence tomography

    Boone, Marc; Draye, Jean Pierre; Verween, Gunther;


    , 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, the epidermis was not removed. In conclusion, HD-OCT imaging permits real-time 3-D visualization of the impact of selected agents on human...... 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...

  19. Survival by Dialysis Modality-Who Cares?

    Lee, Martin B; Bargman, Joanne M


    In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups. In clinical practice, modality choice should be individualized with the aim of maximizing quality of life, patient-reported outcomes, and achieving patient-centered goals. Expected survival is often irrelevant to modality choice. Even for the younger and fitter home hemodialysis population, quality of life, not just duration of survival, is a major priority. On the other hand, increasing evidence suggests that patients with ESRD continue to experience poor quality of life because of high symptom burden, unsolved clinical problems, and unmet needs. Patients care more about how they will live instead of how long. It is our responsibility to align our research with their needs. Only by doing so can we meet the challenges of ESRD patient care in the coming decades.

  20. A major safety overhaul


    A redefined policy, a revamped safety course, an environmental project... the TIS (Technical Inspection and Safety) Division has begun a major safety overhaul. Its new head, Wolfgang Weingarten, explains to the Bulletin why and how this is happening.