Increased fibrosis in a mouse model of anti-laminin 332 mucous membrane pemphigoid remains unaltered by inhibition of aldehyde dehydrogenase

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the basal membrane zone of skin and surface-close epithelia and predominant mucosal lesions. The oral cavity and conjunctivae are most frequently affected, albeit clinical manifestations can also occur on the skin. MMP-associated lesions outside the oral cavity typically lead to scarring. Mechanisms underlying scarring are largely unknown in MMP and effective treatment options are limited. Herein, we assessed the collagen architecture in tissue samples of an antibody-transfer mouse model of anti-laminin-332 MMP. In MMP mice, increased collagen fibril density was observed in skin and conjunctival lesions compared to mice injected with normal rabbit IgG. The extracellular matrix of MMP skin samples also showed altered post-translational collagen cross-linking with increased levels of both lysine- and hydroxylysine-derived collagen crosslinks supporting the fibrotic phenotype in experimental MMP compared to control animals. In addition, we evaluated a potential anti-fibrotic therapy in experimental anti-laminin-332 MMP using disulfiram, an inhibitor of the aldehyde dehydrogenase (ALDH), which has been implicated in immune-mediated mucosal scarring. In addition, disulfiram also acts as a copper chelator that was shown to block lysyl oxidase activity, an enzyme involved in formation of collagen crosslinks. Topical use of disulfiram (300 μM in 2 [w/v] methocel) did not improve ocular lesions in experimental MMP over the 12-day treatment period in disulfiram-treated mice compared to vehicle-treated mice (n=8/group). Furthermore, C57BL6/J mice (n=8/group) were treated prophylactically with 200 mg/kg p.o. disulfiram or the solvent once daily over a period of 12 days. Systemic treatment did not show any reduction in the severity of oral and ocular lesions in MMP mice, albeit some improvement in skin lesions was observed in disulfiram- vs. vehicle-treated mice (p=0.052). No reduction in fibrosis was seen, as assessed by immunohistochemistry. Whilst blocking of ALDH failed to significantly ameliorate disease activity, our data provide new insight into fibrotic processes highlighting changes in the collagenous matrix and cross-linking patterns in IgG-mediated MMP

GENIUS. Generating software-ergonomic user interfaces

GENIUS (GENerator for user Interfaces Using Software-ergonomic rules) comprises a method and the supporting tool environment for the generation of user interfaces from extended data models by means of software-ergonomic rules. The representation of the user interface is based on views defined for the data model. The basic dialogue structure is derived from the data model structure. This ensures the development of task-appropriate user interfaces by transferring the characteristics of the application domain and the user's tasks reflected in the data model to the dialogue structure. The automatic generation of the user interface from the defined views is carried out by a rule-based system with explicit design rules derived from existing guidelines. Output is generated for an existing user interface management system. The software-ergonomic rules in the generation process guarantee the consistent use of interaction objects and a uniformed dialogue structure. The use of the data model as t he starting point for the generation of the user interface ensures the integration of software engineering and user interface design by the consistent use of data for application and user interface development. The generation with GENIUS reduces the development effort and improves the quality of the user interface

Ingenieurmäßige Entwicklung von Informationssystemen. Teil 1. Grundlegende Methoden und Techniken

Bei der Softwareentwicklung ergibt sich die Notwendigkeit, durch standardisierte Abläufe nach anerkannten Regeln Softwareprodukte mit gesicherter Qualität in kurzen Durchlaufzeiten bei hoher funktionaler Wettbewerbsfähigkeit des Produkts herzustellen. In Analogie zur Entwicklung in der teilefertigenden und der montierenden Industrie wurde dafür der Begriff des Software-Engineerings geprägt. Methoden und Techniken (erster Teil), Werkzeuge (zweiter Teil) und Modelle (dritter Teil) des Software-Engineerings werden in diesem dreiteiligen Beitrag vorgestellt