248 research outputs found
Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions
Autoimmune blistering diseases (AIBD) are paradigms of autoantibody-mediated organ-specific autoimmune disorders that involve skin and/or mucous membranes. Compared to other autoimmune diseases, the pathogenicity of autoantibodies in AIBD is relatively well described. Pemphigus is a potentially lethal autoantibody driven autoimmune disorder with a strong HLA class II association. It is mainly characterized by IgG against the desmosomal adhesion molecules desmoglein 3 (Dsg3) and Dsg1. Several murine pemphigus models were developed subsequently, each allowing the analysis of a characteristic feature, such as pathogenic IgG or Dsg3-specific T or B cells. Thus, the models can be employed to preclinically evaluate potentially novel therapies. We here thoroughly summarize past and recent efforts in developing and utilizing pemphigus mouse models for pathomechanistic investigation and therapeutic interventions
Using standardized patients for undergraduate clinical skills training in an introductory course to psychiatry
Background
The goal of this study was to assess the value and acceptance of Standardized or Simulated Patients (SPs) for training clinically inexperienced undergraduate medical students in psychiatric history taking, psychopathological assessment, and communication with psychiatric patients.
Methods
As part of a newly developed introductory course to psychiatry, pairs of 3rd year medical students conducted psychiatric assessments of SPs, including history and psychopathological state, under the supervision of a clinical lecturer. Prior to the assessment, students attended introductory lectures to communication in psychiatry and psychopathology but were clinically inexperienced. After the interview, the students’ summary of their findings was discussed with other students and the lecturer. Students, lecturers, and actors were invited to a survey after the course. Questions for the students included self-reports about perceived learning success and authenticity of the interviews.
Results
41 students, 6 actors and 8 lecturers completed the survey (response rates of 48%, 50%, and 100%, respectively). The survey results indicated that, despite their lack of clinical experience, students learned how to conduct a psychiatric interview, communicate in a non-judgmental and empathetic manner, take a psychiatric history and perform a psychopathological examination. SPs were perceived as authentic. The survey results suggested that this setting allowed for an enjoyable, non-distressful and motivating learning experience within a restricted time frame of just two afternoons.
Conclusion
The results indicated that the SP approach presented is useful for teaching clinical skills in psychiatry to students with limited previous clinical experience and knowledge of psychiatry. We argue that SPs can be used to teach practical psychiatric skills already during an early phase of the curriculum. Limitations of our study include a limited sample size, a temporal gap between the course and the survey, reliance on self-reports, and lack of comparison to alternative interventions
IgG1 and IgG3 are the Major Immunoglobulin Subclasses Targeting Epitopes within the NC16A Domain of BP180 in Pemphigoid Gestationis
EGFR inhibitors erlotinib and lapatinib ameliorate epidermal blistering in pemphigus vulgaris in a non-linear, V-shaped relationship
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Bullous pemphigoid in infants: characteristics, diagnosis and treatment
BACKGROUND: Bullous pemphigoid (BP) in infants is a rare but increasingly reported autoimmune blistering skin disease. Autoantibody reactivity is usually poorly characterized. Current guidelines do not address specific aspects of the infantile form of BP. The objectives of this study are to define clinical and diagnostic characteristics of infantile BP and develop a treatment algorithm. METHODS: Detailed characterization of a current case series of five infants with BP from our departments. Comprehensive analysis of all reported cases (1-12 months) with respect to clinical and laboratory characteristics, treatment and outcome. RESULTS: In total 81 cases were identified (including our own). The mean age was 4.5Â months. Moderately severe and severe disease was seen in 84% of cases. Involvement of hands and feet was present in all cases. Immunofluorescence microscopy was comparable with BP in adults. Where analyzed, the NC16A domain of bullous pemphigoid 180Â kDa antigen/collagen XVII (BP180) was identified as the major target antigen. BP180 NC16A ELISA values in our cohort were significantly higher than in a control cohort of 28 newly diagnosed adult patients. 50% of patients were treated with systemic corticosteroids, 20% with a combination of systemic corticosteroids and dapsone or sulfapyridine and 10% with topical corticosteroids alone. 14% of patients needed a combination of multiple immunosuppressants. All but one patient reached remission. Relapses were rare. CONCLUSIONS: Presentation of infantile BP is often severe with blistering of hands and feet present in all cases. Pathogenesis and diagnostic criteria are comparable to adult BP, yet BP180 NC16A ELISA levels seem to be significantly higher in infants. The overall disease outcome is favorable. Based on the results of this study we propose a treatment algorithm for infantile BP
Identification of Quantitative Trait Loci in Experimental Epidermolysis Bullosa Acquisita
Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. Several lines of evidence underscore the contribution of autoantibodies against type VII collagen (COL7) to the pathogenesis of EBA. Furthermore, EBA susceptibility is associated with the MHC haplotype in patients (HLA-DR2) and in immunization-induced EBA in mice (H2s). The latter study indicated an additional contribution of non-MHC genes to disease susceptibility. To identify non-MHC genes controlling EBA susceptibility, we intercrossed EBA-susceptible MRL/MpJ with EBA-resistant NZM2410/J and BXD2/TyJ as well as Cast mice. Mice of the fourth generation of this four-way autoimmune-prone advanced intercross line were immunized with a fragment of murine COL7 to induce EBA. Anti-COL7 autoantibodies were detected in 84% of mice, whereas deposition of complement at the dermal–epidermal junction (DEJ) was observed in 50% of the animals; 33% of immunized mice presented with overt clinical EBA. Onset of clinical disease was associated with several quantitative trait loci (QTLs) located on chromosomes 9, 12, 14, and 19, whereas maximum disease severity was linked to QTLs on chromosomes 1, 15, and 19. This more detailed insight into the pathogenesis of EBA may eventually lead to new treatment strategies for EBA and other autoantibody-mediated diseases
Protective Endogenous Cyclic Adenosine 5'-Monophosphate Signaling Triggered by Pemphigus Autoantibodies
Pemphigus vulgaris (PV) is an autoimmune skin disease mediated by autoantibodies directed against the cadherin-type cell adhesion molecules desmoglein (Dsg) 3 and Dsg1 and is characterized by loss of keratinocyte cohesion and epidermal blistering. Several intracellular signaling pathways, such as p38MAPK activation and RhoA inhibition, have been demonstrated to be altered following autoantibody binding and to be causally involved in loss of keratinocyte cohesion. In this paper, we demonstrate that cAMP-mediated signaling completely prevented blister formation in a neonatal pemphigus mouse model. Furthermore, elevation of cellular cAMP levels by forskolin/rolipram or β receptor agonist isoproterenol blocked loss of intercellular adhesion, depletion of cellular Dsg3, and morphologic changes induced by Ab fractions of PV patients (PV-IgG) in cultured keratinocytes. Incubation with PV-IgG alone increased cAMP levels, indicating that cAMP elevation may be a cellular response pathway to strengthen intercellular adhesion. Our data furthermore demonstrate that this protective pathway may involve protein kinase A signaling because protein kinase A inhibition attenuated recovery from PV-IgG–induced cell dissociation. Finally, cAMP increase interfered with PV-IgG–induced signaling by preventing p38MAPK activation both in vitro and in vivo. Taken together, our data provide insights into the cellular response mechanisms following pemphigus autoantibody binding and point to a possible novel and more specific therapeutic approach in pemphigus
Diagnostic Value of Linear Fluorescence Along the Basement Membrane of Sweat Gland Ducts in Bullous Pemphigoid
Linear IgG deposits along the basement membrane of adnexa has been proposed to be useful in the diagnosis of bullous pemphigoid (BP), but no controlled studies have been performed. This study evaluated linear IgG fluorescence of the basement membrane of sweat gland ducts (SGD) and other adnexa in perilesional biopsies from patients with BP (n = 64) and controls (n = 82), using direct immunofluorescence microscopy. Fluorescence intensity was graded semi-quantitatively. Positive SGDs were found in 58 (90.6%) patients with BP and 44 (53.7%) controls, a statistically significant difference (p < 0.0001). The sensitivity of positive SGDs for BP was high (90.6%), but the specificity was low (46.3%). Only strong fluorescence intensity was associated with high specificity. In conclusion, positive SGDs in direct immunofluorescence microscopy are highly sensitive for BP;however, only strong fluorescence has acceptable specificity. Weak positivity of SGDs without linear fluorescence of the epidermal basement membrane may not be sufficiently specific for BP
Vision enhancement for maritime search and rescue operations at night and bad weather conditions
During search and rescue operations (SAR) at night and bad weather conditions, the detection of persons in water represents a major challenge. When conventional searchlights are used, the backscattering from rain and fog decreases the detection range. For these conditions, the transportable angegated viewing system (TRAGVIS) was developed, aiming to reduce the effect of backscatter, in particular from close ranges (up to several hundred meters). After data acquisition, image post processing techniques were applied. The objective of the study presented here is to enchance the vision of the image for better object recognition by the operator. In addition automatic object detection methods were tested
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