Karl Landsteiner Institute for Dermatological Research

Sankt Pölten, Austria

Karl Landsteiner Institute for Dermatological Research

Sankt Pölten, Austria
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Just U.,University of Vienna | Dimou E.,University of Vienna | Knobler R.,University of Vienna | Klosner G.,University of Vienna | And 4 more authors.
Experimental Dermatology | Year: 2012

Extracorporeal photopheresis (ECP) is an established therapy for transplant rejection, graft-versus-host disease (GvHD) after allogeneic stem cell transplantation, cutaneous T-cell lymphoma and systemic autoimmune disorders such as systemic sclerosis. Knowledge regarding the in vivo behaviour of the cells after reinfusion is very limited. The aim of this prospective study was to investigate the path of 8-MOP-/UVA-exposed radiolabelled cells after ECP treatment and reinfusion. In this prospective single-centre study, peripheral blood mononuclear cells (PBMC) and neutrophils of 10 patients undergoing ECP as part of their regular treatment were labelled separately with 111In-oxine after exposure to 8-MOP/UVA and prior to reinfusion. The fate of the labelled leucocytes was monitored at 10min, 3.5 and 24h following reinfusion with whole-body scintigraphy. Comparison of distribution patterns showed that PBMC and neutrophils have different kinetic patterns after intravenous reinjection. The most prominent difference was immediate retention of PBMC but not of neutrophils in the lungs corresponding to a signal three times more intense. After 24h, more than 80% of both cell populations could be detected in liver and spleen. By means of a novel tool allowing for tracking of 8-MOP-/UVA-exposed leucocytes in ECP, we could show that organ-specific homing of leucocytes after ECP can be visualized in vivo and that migration patterns differ between PBMC and neutrophils. Based on our results, further studies should (i) extend the morphometric studies described here to specific ECP-responsive conditions and (ii) functionally address the interaction of ECP-modified PBMC with pulmonary tissue in experimental models. © 2012 John Wiley & Sons A/S.

Bublin M.,Medical University of Vienna | Kostadinova M.,Medical University of Vienna | Radauer C.,Medical University of Vienna | Hafner C.,Karl Landsteiner Institute for Dermatological Research | And 5 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Background: Ara h 1, a vicilin; Ara h 2, a 2S albumin; and Ara h 3, a legumin, are major peanut allergens. Ara h 2 is an important predictor of clinical reactivity to peanut, but cosensitization to all 3 allergens is correlated with the severity of patients' symptoms. Objective: We investigated whether cosensitization to these 3 allergens is caused by IgE cross-reactivity, despite the fact that they do not display obvious structural or sequence similarities. Methods: IgEcross-inhibitionswere performedwithpurifiedAra h 1, Ara h 2, andAra h 3 and IgG-depleted sera from10 patients with peanut allergy. After an in silico search for similar peptides, IgE ELISA inhibition assays with synthetic peptides were performed. Results: Ara h 2 inhibited IgE binding to Ara h 1 (average, 86% ± 13%) and Ara h 3 (average, 96% ± 6%). IgE binding to Ara h 2 was inhibited by Ara h 1 by 78% ± 15% and by Ara h 3 by 80% ± 6%. A subsequent sequence comparison showed that these nonhomologous allergens contained several similar surface-exposed peptides. IgE binding to Ara h 2-derived peptides was completely inhibited by Ara h 1 and Ara h 3. A mixture of these peptides reduced IgE binding to Ara h 1 and Ara h 3 by 20% to 60% and to Ara h 2 by 49% to 89%. Conclusion: Occurrence of similar sequences in the 3 major peanut allergens accounts for the high extent of cross-reactivity among them. © 2013 American Academy of Allergy, Asthma &Immunology.

Moser J.,Karl Landsteiner Institute for Dermatological Research | Kriehuber E.,Novartis | Trautinger F.,Karl Landsteiner Institute for Dermatological Research
Skin Pharmacology and Physiology | Year: 2012

Background: Existing sweat tests are either cumbersome, require dedicated technical equipment and/or do not give reliable quantitative results. The present study was performed to develop and describe a rapid and simple test for a practical and quantitative evaluation of sweating. Methods: Cobalt chloride patches were used to collect sweat during exercise and after application of aluminum hydrochloride. Color change from blue to red was recorded and quantified, and the amount of sweat was calculated from a standard curve. Results: Cobalt-chloride-containing patches evaluated with standard office equipment provide a rapid, simple and highly sensitive method for the quantitative measurement of sweating. Conclusions: Possible applications that need to be evaluated in further studies are the diagnosis and monitoring of diseases associated with disordered sweat production and the evaluation of antiperspirants. Copyright © 2012 S. Karger AG, Basel.

Radauer C.,Medical University of Vienna | Adhami F.,Medical University of Vienna | Furtler I.,Medical University of Vienna | Wagner S.,Medical University of Vienna | And 7 more authors.
Molecular Immunology | Year: 2011

Allergies to certain fruits such as banana, avocado, chestnut and kiwi are described in 30-70% of latex-allergic patients. This association is attributed to the cross-reactivity between the major latex allergen hevein and hevein-like domains (HLDs) from fruit class I chitinases. We aimed to assess the extent of cross-reactivity between hevein and HLDs using sera from latex-allergic patients with and without plant food allergy. Hevein and HLDs of latex, banana, and avocado chitinases were expressed in Escherichia coli as fusion proteins with the maltose-binding protein and purified by affinity chromatography. IgE binding to these proteins was studied in sera from 59 latex-allergic patients and 20 banana-allergic patients without latex allergy by ELISA and ELISA inhibition. Additionally, 16,408 allergic patients' sera were tested for IgE binding to hevein, latex chitinase, and wheat germ agglutinin using an allergen microarray. Hevein-specific IgE was detected in 34/59 (58%) latex-allergic patients' sera. HLDs of latex, banana, and avocado chitinases were recognized by 21 (36%), 20 (34%), and 9 (15%) sera, respectively. In contrast, only one of 20 banana-allergic patients without latex allergy was sensitized to chitinase HLDs. In most tested latex-allergic patients' sera, IgE binding to hevein was only partially reduced by preincubation with HLDs. Among hevein-sensitized, latex-allergic patients, the percentage of plant food allergy (15/34. = 44%) was equal to latex-allergic patients without hevein sensitization (11/25. = 44%). In the general allergic population, 230 of 16,408 sera (1.4%) reacted to hevein and/or a hevein-like allergen. Of these, 128 sera showed an isolated sensitization to hevein, whereas only 17 bound to latex chitinase or wheat germ agglutinin without hevein sensitization. In conclusion, the IgE response to HLDs is elicited by hevein as sensitizing allergen in most cases. Despite considerable cross-reactivity between these allergens, no correlation between latex-associated plant food allergy and sensitization to hevein or HLDs was found. © 2010 Elsevier Ltd.

Jung P.,State Hospital St Polten | Trautinger F.,Karl Landsteiner Institute for Dermatological Research
JDDG - Journal of the German Society of Dermatology | Year: 2013

Microscopy of the nailfold capillaries has found increasing use in dermatology, rheumatology and angiology particularly as an important tool to distinguish between primary and secondary Raynaud disease. The best evidence is available in systemic sclerosis where specific capillaroscopic patterns have a high positive predictive value for the development of the disease. Conversely, a regular capillary pattern rules out systemic sclerosis with high degree of probability. PRINCE (prognostic index for nailfold capillaroscopic examination) was developed to identify patients at high risk of developing systemic sclerosis. CSURI (capillaroscopic skin ulcer risk index) should predict the risk of developing digital ulcers in patients with systemic sclerosis with high specificity and sensitivity. As a consequence of recent results a pathologic capillary pattern was integrated by the EULAR Scleroderma Trials and Research Group (EUSTAR) in the diagnostic algorithm of the VEDOSS-Project (very early diagnosis of systemic sclerosis). Capillary patterns may correlate with visceral involvement and capillaroscopy thus has the potential as a screening tool to enable early diagnosis of organ involvement in systemic sclerosis. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Jonak C.,Medical University of Vienna | Mildner M.,Medical University of Vienna | Klosner G.,Medical University of Vienna | Paulitschke V.,Medical University of Vienna | And 5 more authors.
Journal of Dermatological Science | Year: 2011

Background: In human epidermal keratinocytes the expression of hsp27 is closely related to differentiation in vitro and in situ. Objective: We aimed to gain further insight into the role of hsp27 in epidermal differentiation by specific inhibition through siRNA and inhibition of p38-MAPK, the key enzyme of hsp27 phosphorylation. Methods: Normal human keratinocytes (KC) and organotypic skin cultures (SE-skin equivalents) were used. Expression and phosphorylation of hsp27 was inhibited in these models by siRNA and SB203580, a specific inhibitor of p38-MAPK, respectively. Modification of morphology and expression of hsp27 and other differentiation associated proteins was investigated by immunofluorescence, western blot, and RT-PCR. Results: Inhibition of p38-MAPK resulted in a downregulation of hsp27 in KC and SE. Additionally, in the presence of SB203580 Ca2+ induced expression of pro-filaggrin and loricrin was inhibited at the protein level and expression of filaggrin, keratin 10, and transglutaminase 1 at the mRNA level. Addition of SB203580 to SE, as well as hsp27 knockdown in this model resulted in identical patterns of irregular differentiation, disturbance of epidermal layers, and delayed expression of K10. Conclusion: These results provide evidence that the expression of hsp27 and its phosphorylation by p38-MAPK are required for keratinocyte differentiation and for the formation of a regularly stratified epidermis. © 2010 Japanese Society for Investigative Dermatology.

Jonak C.,Medical University of Vienna | Jonak C.,Karl Landsteiner Institute for Dermatological Research | Skvara H.,Medical University of Vienna | Kunstfeld R.,Medical University of Vienna | And 2 more authors.
PLoS ONE | Year: 2011

Background: In clinical diagnostics, as well as in routine dermatology, the increased need for non-invasive diagnosis is currently satisfied by reflectance laser scanning microscopy. However, this technique has some limitations as it relies solely on differences in the reflection properties of epidermal and dermal structures. To date, the superior method of fluorescence laser scanning microscopy is not generally applied in dermatology and predominantly restricted to fluorescein as fluorescent tracer, which has a number of limitations. Therefore, we searched for an alternative fluorophore matching a novel skin imaging device to advance this promising diagnostic approach. Methodology/Principal Findings: Using a Vivascope®-1500 Multilaser microscope, we found that the fluorophore Indocyanine-Green (ICG) is well suited as a fluorescent marker for skin imaging in vivo after intradermal injection. ICG is one of few fluorescent dyes approved for use in humans. Its fluorescence properties are compatible with the application of a near-infrared laser, which penetrates deeper into the tissue than the standard 488 nm laser for fluorescein. ICG-fluorescence turned out to be much more stable than fluorescein in vivo, persisting for more than 48 hours without significant photobleaching whereas fluorescein fades within 2 hours. The well-defined intercellular staining pattern of ICG allows automated cell-recognition algorithms, which we accomplished with the free software CellProfiler, providing the possibility of quantitative high-content imaging. Furthermore, we demonstrate the superiority of ICG-based fluorescence microscopy for selected skin pathologies, including dermal nevi, irritant contact dermatitis and necrotic skin. Conclusions/Significance: Our results introduce a novel in vivo skin imaging technique using ICG, which delivers a stable intercellular fluorescence signal ideal for morphological assessment down to sub-cellular detail. The application of ICG in combination with the near infrared laser opens new ways for minimal-invasive diagnosis and monitoring of skin disorders. © 2011 Jonak et al.

Valencak J.,Medical University of Vienna | Schmid K.,Medical University of Vienna | Trautinger F.,Karl Landsteiner Institute for Dermatological Research | Wallnofer W.,Central Hospital of Bolzano | And 6 more authors.
Journal of Dermatological Science | Year: 2011

Background: Aberrant expression of microRNAs (miRNAs) has been implicated in oncogenesis of various tumors and primary cutaneous T cell lymphomas. Dicer, a ribonuclease III-like enzyme is essential for miRNA processing. Objective: We initiated a retrospective study to characterize the alterations in the expression profile of Dicer in patients with primary cutaneous T cell lymphomas (CTCL). Methods: A total of 50 consecutive patients with primary CTCL were studied, with the majority having mycosis fungoides (n=34). Five patients had primary cutaneous CD 30+ anaplastic large cell lymphoma, four patients each had lymphomatoid papulosis and primary cutaneous CD4-positive small/medium T-cell lymphoma, one primary cutaneous γδ T cell lymphoma, one Sézary syndrome and another subcutaneous panniculitis-like T cell lymphoma of αβ-phenotype. Immunohistochemistry was performed on paraffin sections using a commercially available antibody against Dicer. Intensity of expression was correlated with clinical parameters including disease specific survival (DSS) and time to progression (TTP). Results: After a median follow-up of 74 months (range: 1-271), 12/50 patients (24%) have died. Univariate and multivariate analysis for disease-specific survival showed Dicer expression and stage as a negative predictive factor in the sole group of MF patients (n=34) as well as in the heterogeneous group of patients (n=50), but not gender, histological subtype, primary localization of disease, age and recurrence of lymphoma (p>0.05). Conclusion: Our data suggest Dicer expression as a possible molecular marker in patients with MF and apparently indicate that miRNA(s) might be of clinical relevance in CTCL. © 2011 Japanese Society for Investigative Dermatology.

Jung P.,State Hospital | Jung P.,Karl Landsteiner Institute for Dermatological Research | Trautinger F.,State Hospital | Trautinger F.,Karl Landsteiner Institute for Dermatological Research
JDDG - Journal of the German Society of Dermatology | Year: 2013

Background Nailfold capillaroscopy of fingers is an important tool for diagnosis and monitoring of collagen-vascular diseases. However, little is known about capillaroscopy of toes. Patients and methods Capillaroscopy of the first and second toe was performed in 50 healthy volunteers and 67 patients with chronic venous insufficiency (n = 22), peripheral arterial diseases (n = 24) and collagen-vascular diseases (n = 21) with a capillaroscope under oil immersion with non-polarized light and 50-fold magnification. Results Capillary density of toes (5-9/mm) was reduced compared to fingers (7-11/mm). In contrast to fingers, capillaries of toes show a higher degree of variability. In addition to the classic parallel hairpin form, one may also find tortuous capillaries, ramifications, elongations and capillary bundles. Little difference was noted between patients with vascular and collagen-vascular diseases as compared to volunteers. More ramifications were observed in peripheral arterial diseases and more capillary bundles were seen in collagen-vascular diseases. Pathological patterns such as megacapillaries, avascular areas and hemorrhages were not seen in toes. Conclusions The physiological capillary pattern differs between fingers and toes. The detected pathologic alterations in vascular and collagen-vascular diseases have to be confirmed in further studies. © The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

Trautinger F.,Karl Landsteiner Institute for Dermatological Research
Photodermatology Photoimmunology and Photomedicine | Year: 2011

Among the primary cutaneous T-cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow- and broadband UVB and 8-methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance. © 2011 John Wiley & Sons A/S.

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