Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML

Disease-Independent Skin Recruitment and Activation of Plasmacytoid Predendritic Cells Following Imiquimod Treatment

Background: Imiquimod, an immune response modifier that is used topically to treat different types of skin cancer, induces the production of proinflammatory cytokines that stimulate an antitumor immune response. We assessed characteristics of the imiquimod-induced immune activation in epithelial and lymphoproliferative neoplasias of human skin. We focused on plasmacytoid predendritic cells (PDCs), the primary producer of interferon α (IFN-α) after imiquimod activation in vitro. Methods: We used Affymetrix oligonucleotide arrays to compare gene expression profiles from tumors from 16 patients, 10 with superficial basal cell carcinomas (sBCCs), five with cutaneous T-cell lymphomas (CTCLs), and one with Bowen's disease, before and after topical imiquimod treatment. We used quantitative immunohistochemistry with PDC-specific antibodies against BDCA-2 and CD123 to characterize the PDC population before and after imiquimod treatment in these specimens. Activation status of PDCs from four sBCC patients was assessed by intracellular IFN-α staining and flow cytometry. Results: Expression of various IFN-α-inducible genes (e.g., CIG5, G1P2, OASL, IFIT1, STAT1, IFI35, OAS1, ISG20, MxA, and IRF7), the so-called IFN-α signature, was increased similarly in both sBCC and CTCL lesions after imiquimod treatment. PDCs were recruited and activated in both lesion types, and they produced IFN-α after imiquimod treatment in vivo (mean percentage of PDCs producing IFN-α = 14.5%, 95% confidence interval [CI] = 4.9% to 24%; range = 3.3%-27%, n = 4 lesions). Imiquimod induced similar immune activation patterns in all three diseases, and these patterns were associated with the number of PDCs recruited to the treatment site. Two imiquimod-treated sBCC patients who did not mount an inflammatory response to imiquimod and whose lesions lacked the IFN-α signature after treatment had fewer PDCs in treated lesions compared with other treated patients with such a response. Conclusions: Imiquimod induces immune activation patterns that relate to the number of the PDCs recruited to the treatment site, thus supporting the role of PDC in responsiveness to imiquimod in human

Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

Psoriasis is one of the most common T cell–mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-α represent potential early targets for the treatment of psoriasis

Arbeitsbuch Handlungswissen für Schule und Unterricht

Das Buch vermittelt sowohl grundlegendes als auch aktuelles Handlungswissen für Schule und Unterricht; ebenso sind die KMK-Vorgaben berücksichtigt. Als Zielgruppe sind Studenten der Erziehungswissenschaft und Sozialpädagogik sowie Lehrer im Referendariat gesehen, die eine umfassende Basisorientierung und ein begleitendes Arbeitsmaterial für die schulische Praxis suchen. Folgende Themenbereiche werden behandelt: 1. Pädagogische Professionalität; 2. Wissen über Schüler und Schülerinnen; 3. Curriculum und Lehr-Lernprozesse; 4. Schultheorie; 5. Wissen über Unterricht. Das Buch ist als Arbeitsbuch im Sinne selbstständig-kritischen Lernens konzipiert. Es umfasst Arbeitsfragen, Hinweise auf weiterführende Literatur sowie spezielle Themenbereiche und ein Arbeitsregister. (Verlag

Coincidence of increased soluble interleukin-2 receptors, diminished natural killer cell activity and progressive disease in cutaneous T-cell lymphomas

In 24 patients with cutaneous T-cell lymphomas (CTCL) the clinical course was documented by determination of a tumour burden index (TBI) on entering the study and six months later. In addition to the first TBI, soluble interleukin-2 receptor levels (slL-2R) in the serum were determined using an ELISA technique in 23 patients. In 18 patients natural killer cell (NK) activity was assessed by a 4 h chromium-51 release assay. Statistical analysis revealed a negative correlation between NK activity and an increase of TBI as well as NK activity and slL-2R. Furthermore, there was a strong positive correlation between the increase of TBI and slL-2R. slL-2R and NK activity might be prognostic factors in CTCL patients

Abschlussbericht des Programmträgers zum BLK-Programm: Selbstgesteuertes und kooperatives Lernen in der beruflichen Erstausbildung (SKOLA)

"Im Zeitraum vom Juli 2004 bis Dezember 2008 entwickelten, erprobten und implementierten insgesamt 21 Modellversuche im Rahmen des Modellversuchsprogramms SKOLA (\u27Selbstgesteuertes und kooperatives Lernen in der beruflichen Erstausbildung\u27) verschiedene Ansätze zur Förderung selbstgesteuerten und kooperativen Lernens. Der vorliegende Abschlussbericht stellt den (vorläufigen) Endpunkt dieser intensiven Forschungen das." Eine erweiterte Fassung dieses Berichts ist im Projektverlag erschienen: Dieter Euler, Günter Pätzold: Selbstgesteuertes und kooperatives Lernen in der beruflichen Erstausbildung (SKOLA). Abschlussbericht des Programmträgers. Dortmunder Beiträge zur Pädagogik, Band 44, 2010; 320 Seiten ISSN 1437-4889 ISBN 978-3-89733-214-0. (DIPF/Orig./AG