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Franziska Vielmuth, Vera Rötzer, Eva Hartlieb, Christoph Hirneiß, Jens Waschke, Volker Spindler
Purpose: The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused by autoantibodies against desmosomal adhesion molecules. Patients may suffer conjunctival involvement, yet the underlying mechanisms are largely unclear. We characterized human and murine conjunctiva with respect to the PV autoantigens, and evaluated the effects and mechanisms of PV autoantibodies applied to human conjunctiva ex vivo. Methods: We obtained human conjunctiva specimens from surgical explants and established a short-term culture model to study the alterations induced by antibody fractions of PV patients (PV-IgG)...
August 1, 2016: Investigative Ophthalmology & Visual Science
Brett J Roberts, Robert A Svoboda, Andrew M Overmiller, Joshua D Lewis, Andrew P Kowalczyk, My G Mahoney, Keith R Johnson, James K Wahl
Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics. In this study we have focused on the palmitoylation of the desmosomal cadherin, desmoglein-2 (Dsg2), and characterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured cells...
October 4, 2016: Journal of Biological Chemistry
Kazuya Takamochi, Hiroko Ohmiya, Masayoshi Itoh, Kaoru Mogushi, Tsuyoshi Saito, Kieko Hara, Keiko Mitani, Yasushi Kogo, Yasunari Yamanaka, Jun Kawai, Yoshihide Hayashizaki, Shiaki Oh, Kenji Suzuki, Hideya Kawaji
BACKGROUND: Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed...
September 29, 2016: BMC Cancer
Yue Chen, Hiroo Yokozeki, Kazumoto Katagiri
Significant decreases in hormonal levels at menopause induce physiological and functional discomfort in the skin. Representative changes at menopause are based on "so-called dry skin". However, there is no evidence to explain the mechanism, even though hydration of the stratum corneum (SC) in women at menopause is comparable with that at pre-menopause but is enhanced by hormone replacement therapy. This study objective was to evaluate structural and functional changes in the SC in ovariectomized mice model of menopause...
September 27, 2016: Experimental Dermatology
Susanna Esposito, Sophie Guez, Annalisa Orenti, Gianluca Tadini, Giulietta Scuvera, Laura Corti, Alessia Scala, Elia Biganzoli, Emilio Berti, Nicola Principi
In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0...
2016: International Journal of Molecular Sciences
S Dănescu, J Leppert, R Cosgarea, S Zurac, S Pop, A Baican, C Has
SAM syndrome (OMIM 615508), comprising severe dermatitis, multiple allergies and metabolic wasting, was first described by Samuelov et al in 2013(1) . Cutaneous findings consisted of congenital erythroderma, superficial skin erosions, fine scales and palmoplantar keratoderma and were accompanied by extracutaneous findings including perinatal hyponatremia, food allergies, elevated IgE levels, recurrent infections, metabolic wasting, malabsorbtion, esophageal reflux and eosinophilic esophagitis, cardiac defects, microcephaly and development delay (2,3) ...
September 15, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Feng Cai, Qingqing Zhu, Yingying Miao, Simei Shen, Xin Su, Yi Shi
PURPOSE: Desmoglein-2 (Dsg2) is a cell adhesion protein of the cadherin superfamily. Altered Dsg2 expression is associated with tumorigenesis. This study determined Dsg2 expression in non-small cell lung cancer (NSCLC) tissue specimens for association with clinicopathological and survival data and then assessed the effect of Dsg2 knockdown on regulation of NSCLC cell malignant behaviors in vitro and in nude mouse xenografts. METHODS: qRT-PCR and Western blot were used to detect Dsg2 expression in 28 paired NSCLC and normal tissue samples...
September 14, 2016: Journal of Cancer Research and Clinical Oncology
A von Köckritz, S Ständer, C Zeidler, D Metze, T Luger, G Bonsmann
BACKGROUND: Pemphigus vegetans is a rare variant of pemphigus vulgaris, accounting for 1-2% of all pemphigus diseases. Systemic corticosteroids are the therapy of first choice in combination with immunosuppressants as steroid-sparing agents. OBJECTIVE: To highlight the exceptional but successful use of minocycline/nicotinamide monotherapy in pemphigus vegetans. METHODS: A review of the literature to date about pemphigus vegetans with special emphasis on therapy was performed...
September 7, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Veronika Butin-Israeli, Madelyn C Houser, Mingli Feng, Edward B Thorp, Asma Nusrat, Charles A Parkos, Ronen Sumagin
Neutrophil (PMN) transepithelial migration (TEM) is a hallmark of inflammatory mucosal disorders. PMN TEM is associated with epithelial injury; however, mechanisms involved in this process are not well defined. The current work describes a new mechanism whereby PMN deposition of membrane-derived microparticles (PMN-MPs) onto intestinal epithelial cells (IECs) during TEM leads to loss of epithelial cadherins, thus promoting epithelial injury and increased PMN recruitment. PMN-MPs secreted by activated PMNs during TEM displayed a high level of enzymatically active matrix metalloproteinase (MMP)-9, and were capable of mediating potent effects on IEC integrity...
August 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Zhiling Guo, Qin Hu, Jijing Tian, Li Yan, Chuanyong Jing, Heidi Qunhui Xie, Wenjun Bao, Robert H Rice, Bin Zhao, Guibin Jiang
Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal)...
November 2016: Environmental Pollution
Maggie Chow, Kevin Lai, Richard Ahn, Rashmi Gupta, Sarah Arron, Wilson Liao
BACKGROUND: Adalimumab is an anti-TNF biologic drug that is efficacious in the treatment of psoriasis. However, the effect of adalimumab on genome-wide gene expression changes in skin and peripheral blood is not well characterized.<BR /> METHODS: Thirty adult subjects with > 10% body surface area of chronic plaque psoriasis were recruited for the study. Lesional skin and peripheral blood mononuclear cell samples prior to and one month following treatment with adalimumab were collected...
August 1, 2016: Journal of Drugs in Dermatology: JDD
M-L Lovgren, M A McAleer, A D Irvine, N J Wilson, S Tavadia, M E Schwartz, C Cole, A Sandilands, F J D Smith, M Zamiri
INTRODUCTION: The inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses, characterised by thickening of the epidermis of the palms and soles. No classification system unites satisfactorily clinical presentation, pathology and molecular pathogenesis. There are four patterns of hyperkeratosis: striate, focal, diffuse, and punctate. Mutations in desmoglein-1 (DSG1), a transmembrane glycoprotein, have been reported primarily in striate, but also in focal and diffuse PPKs...
August 18, 2016: British Journal of Dermatology
Asuka Yoshifuku, Kazuyasu Fujii, Hisao Kawahira, Hiromi Katsue, Atsunori Baba, Yuko Higashi, Yumi Aoyama, Takuro Kanekura
Pemphigus vulgaris (PV) is an autoimmune blistering disease elicited by anti-desmoglein (DsG) 3 antibody. Although skin lesions tend to be distributed over the entire body, in some patients, they are confined to a restricted area. We report two patients who presented with long-lasting localized PV without detectable anti-DsG antibodies after suffering antibody-positive systemic PV. Initial treatment with prednisolone (PSL) was successful in both patients, but a local relapse occurred on the cheek or lower lip after a reduction in the PSL dose...
July 2016: Indian Journal of Dermatology
D Miyamoto, M N Sotto, C S V Otani, L M I Fukumori, N V Pereira, C G Santi, C W Maruta, M N N Burnier, M M Rebeis, V Aoki
BACKGROUND: Erythroderma is a clinical skin syndrome shared by patients with cutaneous disorders of distinct etiologies as a result of the combined actions of chemokines, adhesion molecules, and cytokines, such as vascular endothelial growth factor (VEGF). OBJECTIVE: To evaluate the profile of serum levels of VEGF and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) in pemphigus foliaceus (PF) patients with erythroderma. METHODS: We conducted a retrospective study, which included 1) a chart review of all PF patients from the Autoimmune Blistering Clinic, University of Sao Paulo, Brazil, from January 1991 to December 2014, together with an evaluation of demographic variables, hospitalization duration and complications and 2) analysis of the circulating VEGF and sVEGFR-1 levels in PF patients with erythroderma by ELISA...
August 11, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Sara N Stahley, Emily I Bartle, Claire E Atkinson, Andrew P Kowalczyk, Alexa L Mattheyses
Desmosomes are macromolecular junctions responsible for providing strong cell-cell adhesion. Because of their size and molecular complexity, the precise ultrastructural organization of desmosomes is challenging to study. Here, we used direct stochastic optical reconstruction microscopy (dSTORM) to resolve individual plaque pairs for inner and outer dense plaque proteins. Analysis methods based on desmosomal mirror symmetry were developed to measure plaque-to-plaque distances and create an integrated map. We quantified the organization of desmoglein 3, plakoglobin and desmoplakin (N-terminal, rod and C-terminal domains) in primary human keratinocytes...
August 1, 2016: Journal of Cell Science
Sharada Sawant, Harsh Dongre, Archana Kumari Singh, Shriya Joshi, Daniela Elena Costea, Snehal Mahadik, Chetan Ahire, Vidhi Makani, Prerana Dange, Shilpi Sharma, Devendra Chaukar, Milind Vaidya
To study multistep tumorigenesis process, there is a need of in-vitro 3D model simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue models comprising various stages of neoplastic progression of tongue tumorigenesis and to evaluate the utility of these models to investigate the role of stromal fibroblasts in maintenance of desmosomal anchoring junctions using transmission electron microscopy. We reconstituted in-vitro models representing normal, dysplastic, and malignant tissues by seeding primary keratinocytes on either fibroblast embedded in collagen matrix or plain collagen matrix in growth factor-free medium...
2016: PloS One
Ewa Stypczyńska, Waldemar Placek, Barbara Zegarska, Rafał Czajkowski
Palmoplantar keratoderma (PPK) is a heterogeneous group of hereditary and acquired disorders characterized by abnormal thickening of the palms and soles. There are three clinical patterns: diffuse, focal, and punctuate. Palmoplantar keratodermas can be divided into the following functional subgroups: disturbed gene functions in structural proteins (keratins), cornified envelope (loricrin, transglutaminase), cohesion (plakophilin, desmoplakin, desmoglein 1), cell-to-cell communication (connexins) and transmembrane signal transduction (cathepsin C)...
June 2016: Acta Dermatovenerologica Croatica: ADC
Ken Muramatsu, Wataru Nishie, Ken Natsuga, Yasuyuki Fujita, Hiroaki Iwata, Tamaki Yamada, Emi Yamashita, Takuya Asaka, Hiroshi Shimizu
Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa of unknown etiology. Clinically, the erosive type of OLP (erosive OLP) can show features similar to those of pemphigus vulgaris (PV), an autoimmune blistering disorder in which desmoglein (Dsg)3 is targeted. In addition to clinical and histopathological findings, immunological studies, including direct immunofluorescence (IF), indirect IF and enzyme-linked immunosorbent assay (ELISA) that detect autoantibodies to Dsg3, are helpful in differentiating erosive OLP from PV...
July 26, 2016: Journal of Dermatology
J A McGovern, C Meinert, S J de Veer, B G Hollier, T J Parker, Z Upton
BACKGROUND: Epidermal homeostasis is maintained through the balance between keratinocyte proliferation, differentiation and desquamation, however human skin equivalent (HSE) models are known to excessively differentiate. In native tissue, proteases such as kallikrein-related peptidase (KLK) 5, and KLK7 cleave the extracellular components of corneodesmomes; proteins corneodesmosin (CDSN), desmocollin 1 (DSC1) and desmoglein 1 (DSG1), loosening the cellular connections and enabling desquamation...
July 21, 2016: British Journal of Dermatology
Frane Banovic, Keith Linder, Thierry Olivry
BACKGROUND: The microscopic and microbial features of the spreading epidermal collarettes of canine exfoliative superficial pyodermas are poorly characterized. OBJECTIVES: To characterize the clinical, cytological, microbial and histopathological features of epidermal collarettes in five dogs. RESULTS: Cytology from the margins of collarettes identified neutrophils, extracellular and intracellular cocci within neutrophils but no acantholytic keratinocytes...
July 18, 2016: Veterinary Dermatology
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