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https://www.readbyqxmd.com/read/29755451/autoantibody-signaling-in-pemphigus-vulgaris-development-of-an-integrated-model
#1
REVIEW
Thomas Sajda, Animesh A Sinha
Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs) to keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3, and to a lesser extent, desmoglein 1, cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion, although additional autoAbs, whose role in blister formation is still unclear, are also known to be present in PV patients...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29750433/absence-of-a-primary-role-for-ttn-missense-variants-in-arrhythmogenic-cardiomyopathy-from-a-clinical-and-pathological-perspective
#2
Kai Chen, Jiangping Song, Zhen Wang, Man Rao, Liang Chen, Shengshou Hu
BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inheritable heart disease characterized by fibro-fatty replacement of the myocardium. TTN missense variants were previously reported as a pathogenic factor for ACM. HYPOTHESIS: TTN missense variants are commonly identified in ACM, but have limited effect on the phenotype of ACM. METHODS: We sequenced 15 ACM-related genes in 35 patients who had a heart transplantation and quantified myocardium, and fibrous and adipose tissue in blocks of the explanted heart...
May 11, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29744885/morphologic-mimicry-acantholytic-squamous-cell-carcinoma-in-nondermal-locations-a-literature-review
#3
REVIEW
Mustafa Mohammad, Rebecca Wilcox
Acantholytic squamous cell carcinoma (acantholytic SCC) is a variant of SCC in which acantholysis develops owing to the loss of desmosomal adhesion proteins. This loss of cell-cell adhesion leads to morphologic changes that have the potential to mimic other tumor types, such as angiosarcoma or signet ring cell adenocarcinoma. Acantholytic SCC characteristically occurs in sun-exposed skin of elderly patients; however, it can occur in nondermal locations. We present a review of the literature describing cases of nondermal acantholytic SCC...
May 9, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29743597/mastl-overexpression-promotes-chromosome-instability-and-metastasis-in-breast-cancer
#4
Samuel Rogers, Rachael A McCloy, Benjamin L Parker, David Gallego-Ortega, Andrew M K Law, Venessa T Chin, James R W Conway, Dirk Fey, Ewan K A Millar, Sandra O'Toole, Niantao Deng, Alexander Swarbrick, Paul D Chastain, Anthony J Cesare, Paul Timpson, C Elizabeth Caldon, David R Croucher, David E James, D Neil Watkins, Andrew Burgess
MASTL kinase is essential for correct progression through mitosis, with loss of MASTL causing chromosome segregation errors, mitotic collapse and failure of cytokinesis. However, in cancer MASTL is most commonly amplified and overexpressed. This correlates with increased chromosome instability in breast cancer and poor patient survival in breast, ovarian and lung cancer. Global phosphoproteomic analysis of immortalised breast MCF10A cells engineered to overexpressed MASTL revealed disruption to desmosomes, actin cytoskeleton, PI3K/AKT/mTOR and p38 stress kinase signalling pathways...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29740444/keratinocyte-binding-assay-identifies-anti-desmosomal-pemphigus-antibodies-where-other-tests-are-negative
#5
Federica Giurdanella, Albertine M Nijenhuis, Gilles F H Diercks, Marcel F Jonkman, Hendri H Pas
The serological diagnosis of pemphigus relies on the detection of IgG autoantibodies directed against the epithelial cell surface by indirect immunofluorescence (IIF) on monkey esophagus and against desmoglein 1 (Dsg1) and Dsg3 by ELISA. Although being highly sensitive and specific tools, discrepancies can occur. It is not uncommon that sera testing positive by ELISA give a negative result by IIF and vice versa . This brings diagnostic challenges wherein pemphigus has to be ascertained or ruled out, especially when no biopsy is available...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29723998/the-ebv-encoded-oncoprotein-lmp1-induces-an-epithelial-to-mesenchymal-transition-emt-via-its-ctar1-domain-through-integrin-mediated-erk-mapk-signalling
#6
Mhairi A Morris, Louise Laverick, Wenbin Wei, Alexandra M Davis, Samantha O'Neill, Liam Wood, Jack Wright, Christopher W Dawson, Lawrence S Young
The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression...
May 1, 2018: Cancers
https://www.readbyqxmd.com/read/29722422/expression-of-plakophilin-3-in-diffuse-malignant-pleural-mesothelioma
#7
Silvija Mašić, Luka Brčić, Božo Krušlin, Ana Šepac, Biserka Pigac, Dinko Stančić-Rokotov, Marko Jakopović, Sven Seiwerth
Diffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm still posing major diagnostic, prognostic and therapeutic challenges. Plakophilins are structural proteins considered to be important for cell stability and adhesion in both tumor and normal tissues. Plakophilin 3 is a protein present in desmosomes of stratified and simple epithelia of normal tissues with presence in malignant cells of various tumors where it participates in the process of tumorigenesis. The aim of this study was to investigate the expression of plakophilin 3 protein in DMPM, but also to study its prognostic significance and relation to histologically accessible parameters of aggressive growth...
May 3, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29709087/identification-of-sarcomeric-variants-in-probands-with-a-clinical-diagnosis-of-arrhythmogenic-right-ventricular-cardiomyopathy-arvc
#8
Brittney Murray, Edgar T Hoorntje, Anneline S J M Te Riele, Crystal Tichnell, Jeroen F van der Heijden, Harikrishna Tandri, Maarten P van den Berg, Jan D H Jongbloed, Arthur A M Wilde, Richard N W Hauer, Hugh Calkins, Daniel P Judge, Cynthia A James, J Peter van Tintelen, Dennis Dooijes
AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden death. Currently 60% of patients meeting Task Force Criteria (TFC) have an identifiable mutation in one of the desmosomal genes. As much overlap is described between other cardiomyopathies and ARVC, we examined the prevalence of rare, possibly pathogenic sarcomere variants in the ARVC population. METHODS: One hundred and thirty-seven (137) individuals meeting 2010 TFC for a diagnosis of ARVC, negative for pathogenic desmosomal variants, TMEM43, SCN5A, and PLN were screened for variants in the sarcomere genes (ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNC1, TNNI3, TNNT2 and TPM1) through either clinical or research genetic testing...
April 30, 2018: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29704884/molecular-basis-of-the-skin-barrier-structures-revealed-by-electron-microscopy
#9
REVIEW
Akemi Ishida-Yamamoto, Satomi Igawa, Mari Kishibe
The barrier function of skin is indispensable for terrestrial animals. This function is mainly carried out by the epidermis, more specifically by its granular and cornified layers. The major structural components associated with this function are the intercellular lipid layer, desmosomes, corneodesmosomes, tight junctions, cornified cell envelope, and keratin filaments. In this review, we discuss the current knowledge of their ultrastructure, their molecular basis, and their relevance to skin disease. This article is protected by copyright...
April 28, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29688316/diagnostic-and-therapeutic-strategies-for-arrhythmogenic-right-ventricular-dysplasia-cardiomyopathy-patient
#10
Weijia Wang, Cynthia A James, Hugh Calkins
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare inherited heart muscle disease characterized by ventricular tachyarrhythmia, predominant right ventricular dysfunction, and sudden cardiac death. Its pathophysiology involves close interaction between genetic mutations and exposure to physical activity. Mutations in genes encoding desmosomal protein are the most common genetic basis. Genetic testing plays important roles in diagnosis and screening of family members. Syncope, palpitation, and lightheadedness are the most common symptoms...
April 23, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29687905/modulation-of-intestinal-paracellular-transport-by-bacterial-pathogens
#11
Jennifer Lising Roxas, V K Viswanathan
The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport...
March 25, 2018: Comprehensive Physiology
https://www.readbyqxmd.com/read/29678907/14-3-3-proteins-regulate-desmosomal-adhesion-via-plakophilins
#12
Katrin Rietscher, René Keil, Annemarie Jordan, Mechthild Hatzfeld
Desmosomes are essential for strong intercellular adhesion and are abundant in tissues exposed to mechanical strain. At the same time, desmosomes need to be dynamic to allow for remodeling of epithelia during differentiation or wound healing. Phosphorylation of desmosomal plaque proteins appears essential for desmosome dynamics. However, the mechanisms how context-dependent post-translational modifications regulate desmosome formation, dynamics or stability are incompletely understood. Here, we show that growth factor signaling regulates the phosphorylation-dependent association of plakophilins 1 and 3 with 14-3-3 protein isoforms and uncover unique and partially antagonistic functions of members of the 14-3-3 family in the regulation of desmosomes...
April 20, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29643851/atomic-force-microscopy-provides-new-mechanistic-insights-into-the-pathogenesis-of-pemphigus
#13
REVIEW
Franziska Vielmuth, Volker Spindler, Jens Waschke
Autoantibodies binding to the extracellular domains of desmoglein (Dsg) 3 and 1 are critical in the pathogenesis of pemphigus by mechanisms leading to impaired function of desmosomes and blister formation in the epidermis and mucous membranes. Desmosomes are highly organized protein complexes which provide strong intercellular adhesion. Desmosomal cadherins such as Dsgs, proteins of the cadherin superfamily which interact via their extracellular domains in Ca2+ -dependent manner, are the transmembrane adhesion molecules clustered within desmosomes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29630095/pathogenicity-of-high-risk-hpv-infection-in-pseudocondyloma-of-vulvae-and-its-carcinogenicity-in-inducing-cervical-lesions
#14
P-F Song, J-Y Chen, Q He, J Wang, J Xu
OBJECTIVE: To identify high-risk human papillomavirus (HPV) infection in pseudocondyloma of vulvae (PV) and the causal relationship between high-risk HPV infection and cervical cancer. PATIENTS AND METHODS: The patients were divided into condyloma acuminatum group, PV groups and PV high-risk HPV infection group according to the clinical data and morphological features. Condyloma acuminatum group and PV group were two control groups. The exfoliated cells were detected and typed by human HPV nucleic acid typing kit...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29616033/keratins-regulate-p38mapk-dependent-desmoglein-binding-properties-in-pemphigus
#15
Franziska Vielmuth, Elias Walter, Michael Fuchs, Mariya Y Radeva, Fanny Buechau, Thomas M Magin, Volker Spindler, Jens Waschke
Keratins are crucial for the anchorage of desmosomes. Severe alterations of keratin organization and detachment of filaments from the desmosomal plaque occur in the autoimmune dermatoses pemphigus vulgaris and pemphigus foliaceus (PF), which are mainly caused by autoantibodies against desmoglein (Dsg) 1 and 3. Keratin alterations are a structural hallmark in pemphigus pathogenesis and correlate with loss of intercellular adhesion. However, the significance for autoantibody-induced loss of intercellular adhesion is largely unknown...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29606507/human-isl1-ventricular-progenitors-self-assemble-into-an-in-vivo-functional-heart-patch-and-preserve-cardiac-function-post-infarction
#16
Kylie S Foo, Miia L Lehtinen, Chuen Yan Leung, Xiaojun Lian, Jiejia Xu, Wendy Keung, Lin Geng, Terje R S Kolstad, Sebastian Thams, Andy On-Tik Wong, Nicodemus Wong, Kristine Bylund, Chikai Zhou, Xiaobing He, Shao-Bo Jin, Jonathan Clarke, Urban Lendahl, Ronald A Li, William E Louch, Kenneth R Chien
The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo...
February 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29606362/usefulness-of-genetic-study-by-next-generation-sequencing-in-high-risk-arrhythmogenic-cardiomyopathy
#17
Amalio Ruiz Salas, José Peña Hernández, Carmen Medina Palomo, Alberto Barrera Cordero, Fernando Cabrera Bueno, José Manuel García Pinilla, Ana Guijarro, Luis Morcillo-Hidalgo, Manuel Jiménez Navarro, Juan José Gómez Doblas, Eduardo de Teresa, Javier Alzueta
INTRODUCTION AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. METHODS: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015...
March 29, 2018: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29573413/herpetiform-pemphigus-with-characteristic-transmission-electron-microscopic-findings-of-various-sized-ballooning-vacuoles-in-keratinocytes-without-acantholysis
#18
N Ishiura, M Tamura-Nakano, H Okochi, C Tateishi, M Maki, Y Shimoda, N Ishii, T Hashimoto, T Tamaki
We report a unique Japanese female case of herpetiform pemphigus (HP) who had immunoglobulin G (IgG) autoantibodies reactive with non-desmosomal sites of keratinocytes, and presented characteristic transmission electron microscopic (TEM) findings of various-sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular edematous erythemas with small blisters lining at the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils...
March 24, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29567352/mechanical-forces-in-skin-disorders
#19
REVIEW
Chao-Kai Hsu, Hsi-Hui Lin, Hans I-Chen Harn, Michael W Hughes, Ming-Jer Tang, Chao-Chun Yang
Mechanical forces are known to regulate homeostasis of the skin and play a role in the pathogenesis of skin diseases. The epidermis consists of keratinocytes that are tightly adhered to each other by cell junctions. Defects in keratins or desmosomal/hemidesmosomal proteins lead to the attenuation of mechanical strength and formation of intraepidermal blisters in the case of epidermolysis bullosa simplex. The dermis is rich in extracellular matrix, especially collagen, and provides the majority of tensile force in the skin...
June 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29566927/blistering-diseases-in-the-mature-patient
#20
Ines Lakoš Jukić, Sandra Jerković Gulin, Branka Marinović
Autoimmune blistering diseases (AIBD) are a group of chronic diseases affecting the skin and mucous membranes, with different presentation, clinical course, histologic and immunopathologic findings, and different therapeutic approach. Blisters develop as a result of autoantibodies directed against distinct adhesion structures within desmosomes or within the basement membrane zone. The most common AIBD that develops in the elderly is bullous pemphigoid (previously also named "pemphigoid senilis"), but mature patients can also present with other AIBD as mucous membrane pemphigoid, epidermolysis bullosa acquisita, paraneoplastic pemphigus, pemphigus vulgaris, pemphigus foliaceus, linear IgA dermatosis, and dermatitis herpetiformis...
March 2018: Clinics in Dermatology
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