FOXP3+CD25− Tumor Cells with Regulatory Function in Sézary Syndrome

Cutaneous T-cell lymphoma (CTCL) has been suggested by in vitro experiments to represent a malignant CD4+ T-cell proliferation with a regulatory T-cell (Treg) phenotype (CD4+CD25+FOXP3+). We investigated percentages of FOXP3+ and CD25+ cells in the blood of 15 Sézary, 14 mycosis fungoides (MF), and 10 psoriasis (Pso) patients and 20 normal healthy donors (NHDs). We found similar numbers of FOXP3+ cells in MF (10.4% of blood CD4+ cells) and Pso (11.1%) patients and NHDs (9.8%). In 8 of 15 (53%) Sézary patients, significantly reduced percentages of FOXP3+ cells were seen in blood (2.9%) and skin (10.4%). Interestingly, 6 of 15 (40%) Sézary patients showed significantly increased percentages of FOXP3+ cells (39.7% (blood), 20.3% (skin)); however, these cells did not express CD25. In these latter patients, clone-specific TCR-Vβ-chain antibodies were used to demonstrate that these FOXP3+CD25− cells were monoclonal CTCL tumor cells. FOXP3+CD25− CTCL tumor cells showed a highly demethylated status of the foxp3 gene locus similar to Treg cells, and they were functionally able to suppress IL-2 mRNA induction in TCR-stimulated conventional T cells. Thus, FOXP3+CD25− CTCL tumor cells with functional features of Treg cells define a subgroup of Sézary patients who might carry a different prognosis and might require differential treatment

Ácidos grasos como marcadores de las relaciones tróficas entre el sestón, el zooplancton crustáceo y el sifonóforo Nanomia cara en Georges Basin y el cañón Oceanographer (NO Atlántico)

[EN] Fatty acid concentrations expressed as percentages of total fatty acid pools in seston, stage V copepodites of Calanus finmarchicus, adults of the euphausiid Meganyctiphanes norvegica, and the physonect siphonophore Nanomia cara were used to elucidate trophic links in Georges Basin and Oceanographer Canyon in September 2003. Seston at both locations was refractory and comprised mainly of saturated fatty acids. Phytoplankton did not contribute significantly to the fatty acid composition of seston or higher trophic levels. Only four fatty acids, i.e. 14:0, 16:0, 16:1 (n–7) and 18:1 (n–7), were transferred from seston to C. finmarchicus or M. norvegica, which suggested weak trophic interactions. Fatty acids transferred from the two species of crustaceans to N. cara included the same four fatty acids, along with three polyunsaturated fatty acids found in relatively high concentrations in both crustaceans, i.e. 20:3 (n–6), 20:5 (n–3) and 22:6 (n–3). In addition, 18:1 (n–9), which occurred in relatively high concentrations only in M. norvegica, and 18:0 and 18:2 (n–6), which were found in low concentrations in both crustaceans, also appeared to be transferred to N. cara. Overall, fatty acid trophic markers proved useful for identifying trophic links to N. cara[ES] En este estudio se utilizaron las concentraciones de ácidos grasos (expresadas como porcentajes) para identificar posibles relaciones tróficas entre el seston, el estadio V (copepoditos) de Calanus finmarchicus, los adultos del eufáusido Meganyctiphanes norvegica, y el sifonóforo fisonecto Nanomia cara en Georges Basin y el cañón submarino Oceanographer durante Septiembre de 2003. En ambos lugares el seston era muy refractario y compuesto básicamente por ácidos grasos saturados. El fitoplancton no contribuyó de forma significativa a la composición de ácidos grasos del seston o de niveles tróficos superiores. Sólo cuatro ácidos grasos [14:0, 16:0, 16:1 (n–7) y 18:1 (n–7)] se transfirieron potencialmente del seston a C. finmarchicus o M. norvegica, lo que sugiere una débil conexión trófica entre estos eslabones de la cadena. Los ácidos grasos transferidos de las dos especies de zooplancton crustáceo a N. cara incluyen los mismos descritos más arriba y otros tres ácidos grasos poliinsaturados [20:3 (n–6), 20:5 (n–3) y 22:6 (n–3)] encontrados en concentraciones relativamente elevadas en ambos crustáceos. Además, tanto el 18:1 (n–9) (encontrado en elevadas concentraciones en M. norvegica) y los 18:0 y 18:2 (n–6) (encontrados en bajas concentraciones en ambas especies de crustáceos) se transfieren a N. cara. Los ácidos grasos demuestran ser una herramienta útil para identificar conexiones tróficas en N. caraA grant to MJY from the National Science Foundation (NSF-0002493), the European Project EUROGEL, and USDA CRIS Project FLA-FAS-03978 supported this workPeer reviewe

Pomalidomide-based treatment in relapsed refractory mulitiple myeloma: Analysis of baseline characteristics and safety profile of patients who died in the European post approval safety study: PS1418

n/

The Human Proteins MBD5 and MBD6 Associate with Heterochromatin but They Do Not Bind Methylated DNA

BACKGROUND: MBD5 and MBD6 are two uncharacterized mammalian proteins that contain a putative Methyl-Binding Domain (MBD). In the proteins MBD1, MBD2, MBD4, and MeCP2, this domain allows the specific recognition of DNA containing methylated cytosine; as a consequence, the proteins serve as interpreters of DNA methylation, an essential epigenetic mark. It is unknown whether MBD5 or MBD6 also bind methylated DNA; this question has interest for basic research, but also practical consequences for human health, as MBD5 deletions are the likely cause of certain cases of mental retardation. PRINCIPAL FINDINGS: Here we report the first functional characterization of MBD5 and MBD6. We have observed that the proteins colocalize with heterochromatin in cultured cells, and that this localization requires the integrity of their MBD. However, heterochromatic localization is maintained in cells with severely decreased levels of DNA methylation. In vitro, neither MBD5 nor MBD6 binds any of the methylated sequences DNA that were tested. CONCLUSIONS: Our data suggest that MBD5 and MBD6 are unlikely to be methyl-binding proteins, yet they may contribute to the formation or function of heterochromatin. One isoform of MBD5 is highly expressed in oocytes, which suggests a possible role in epigenetic reprogramming after fertilization

Intracerebral Human Regulatory T Cells: Analysis of CD4+CD25+FOXP3+ T Cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients

Impaired suppressive capacity of CD4+CD25+FOXP3+ regulatory T cells (Treg) from peripheral blood of patients with multiple sclerosis (MS) has been reported by multiple laboratories. It is, however, currently unresolved whether Treg dysfunction in MS patients is limited to reduced control of peripheral T cell activation since most studies analyzed peripheral blood samples only. Here, we assessed early active MS lesions in brain biopsies obtained from 16 patients with MS by FOXP3 immunohistochemistry. In addition, we used six-color flow cytometry to determine numbers of Treg by analysis of FOXP3/CD127 expression in peripheral blood and cerebrospinal fluid (CSF) of 17 treatment-naïve MS patients as well as quantities of apoptosis sensitive CD45ROhiCD95hi cells in circulating and CSF Treg subsets. Absolute numbers of FOXP3+ and CD4+ cells were rather low in MS brain lesions and Treg were not detectable in 30% of MS biopsies despite the presence of CD4+ cell infiltrates. In contrast, Treg were detectable in all CSF samples and Treg with a CD45ROhiCD95hi phenotype previously shown to be highly apoptosis sensitive were found to be enriched in the CSF compared to peripheral blood of MS patients. We suggest a hypothetical model of intracerebral elimination of Treg by CD95L-mediated apoptosis within the MS lesion

Josef Ignaz Mildorfer 1719-1775

This monograph on Joseph Ignaz Mildorfer (1719-1775) consists of forteen chapters, that after having given an overall curriculum, depict the various stations in the painter's working process. Special emphasis has been given to such criteria as the socio-economic, political and esthetic impacts, that shaped the development of this intriguing artist. Mildorfer was born into a distinguished family of painters in Innsbruck, where he was taught the basics of his profession. However, he was also exposed to the newly imported paintings from southern Germany, which at this time sparked Tyrolian tradition with international flavor. Partly due to those early stimuli, the young painter managed to instantly gain the renowned "big prize" of the Academy, upon his arrival in Imperial Vienna. This distinction was a prerequisite to any further career. Praised by his contemporaries as the most prodigious pupil of Paul Troger, Mildorfer soon was offered remarkable employments. His first major task, the complete decoration of the pilgrimage church at Hafnerberg near Vienna, comprising works in fresco and oil was soon to be followed by a commission from the Imperial court. But Austria was plagued by a raging War of Succession, which cast its shadow upon the job market, forcing Mildorfer to venture out into alternative fields. This he found in the painting of battlescenes. In this genre the young artist produced works of such rebellious intenseness that surpassed all his colleagues' endeavors and saved him a special niche. It might well be that those particular paintings drew the attention of the last great sponsers of the monarchy to Mildorfer, resulting in his being appointed painter of the court to the Duchess of Savoy, neé Maria Theresia Princess of Liechtenstein. (By way of scholarly work in the Princely Archives of Liechtenstein we have now established answers to questions regarding character and extend of Mildorfers work for the Duchess, that up till now has been obscured). In addition this period marked the beginning of a long lasting relationship with various branches of the Esterházy family, culminating in Mildorfer's appointment to Esterháza. Here he was commissioned to paint al fresco in Duke Nikolaus Esterházy's castle, one of the last manifestations of feudal style, the elaborate adornment of which promted the Duke with the attribute "The Magnificent". When Mildorfer was elected Professor at the Academy (kaiserlich-königliche Hofakademie der Mahler, Bildhauer und Baukunst) this not only marked the zenith of his career but also had major impact on one of the most thrilling phenomena within eighteenth century Viennese art. It was under his leadership that a movement took center stage, that was aprostophized the "Einheitsstil der Wiener Akademie". Carried out by an array of his scholars, notably Franz Anton Maubertsch this faszinating manifestation had Mildorfer's ideas at its core. With his contributions in the Crown Lands of the Habsburg monarchy in mind, his work makes him a typical Central-European artist of the eighteenth century. However some of his lesser graspable traits can only be understood out of the "Zeitgeist" and must be explained under the term of "painter of the sensibility". Since Mildorfer is the link between Paul Troger, his teacher and Franz Anton Maulbertsch, his student, a comprehensive biography of this artist is an absolute must. Only that makes a profound understanding of the third generation of Austrian barock-painting possible.Die vorliegende Monographie über den Maler Joseph Ignaz Mildorfer (1719-1775) umfasst vierzehn Kapitel, die mit dem Lebenslauf beginnend die verschiedenen Etappen im Werk des Malers veranschaulichen. Dabei wurde grosser Wert auf die soziologischen, politischen und ästhetischen Kriterien gelegt, welche die Entwicklung dieses eigenwilligen Künstlers bestimmten. In eine angesehene Malerfamilie in Innsbruck geboren, erlebte Mildorfer neben seiner konventionellen Ausbildung in der väterlichen Werkstatt hier auch den Beginn einer internationalen Monumentalmalerei, die erst durch den Import süddeutscher Maler auf tiroler Boden um sich griff. Mit diesen frühen Anregungen versehen, gelang es dem jungen Maler bei seiner Ankunft in der Kaiserstadt denn auch mit erstaunlicher Sicherheit den, für eine erfolgreiche Karriere imperativen, grossen Preis der Wiener Akademie zu gewinnen. Im Fahrwasser Paul Trogers, als dessen begabtester Schüler er von den Zeitgenossen gerühmt wurde, stellten sich in rascher Folge prestigereiche Angebote ein. Dem erstaunlich grossen Erstlingswerk, der malerischen Gesamtausstattung der Wallfahrtskirche am Hafnerberg, schloss sich bald der erste kaiserliche Auftrag an. Doch Österreich befand sich im Erbfolgekrieg, der die künstlerische Auftragssituation ernstlich bedrohte und auch Mildorfer zwang, nach Alternativen zu suchen. Und solche fand er in der Schlachtenmalerei. In diesem Genre schuf der junge Künstler Werke von einer aufrührenden Intensität, die ihn weit über seine Kollegen an der Akademie herausragen liessen, und ihm eine eigene Nische boten. Sicherlich machten gerade diese Bilder die letzten grossen Mäzene der Monarchie auf Mildorfer aufmerksam, was zu seiner Berufung als Hofmaler der Herzogin Maria Theresia von Savoyen, geborener Prinzessin von Liechtenstein führte, und eine lang anhaltende Zusammenarbeit mit den verschiedenen Zweigen der Familie Esterházy nach sich zog. Als Krönung rief Nikolaus Fürst Esterházy Mildorfer schliesslich nach Esterháza, um jenes Schloss zu freskieren, dessen aufwendige Gestaltung seinem Besitzer den Beinamen "der Prachtliebende" bescherte. (Die gründliche Aufarbeitung des Fürstlich Liechtensteinischen Archivs in Vaduz beantwortet nun endlich die Frage nach Art und Ausmass des tradierten, aber nie geklärten Arbeitsverhältnisses unseres Malers mit dem Hause Liechtenstein). Mildorfers Wahl zum wiener Akademieprofessor markierte nicht nur den Höhepunkt dieses Künstlerlebens, sondern spielte auch ganz wesentlich in eines der spannendsten Kapitel der wiener Kunst des 18. Jahrhunderts hinein. Unter seiner Ägide nämlich entstand hier der vielzitierte "Einheitsstil der Wiener Akademie", der von der Fülle seiner Schüler, allen voran Franz Anton Maulbetsch getragen wurde und Mildorfer zum Urheber dieses faszinierenden Phänomens macht. Die Arbeiten in den ehemaligen Kronländern kompletieren sein Werk als das eines typischen Mitteleuropäers des 18. Jahrhunderts. Manche, der oft schwer nachvollziehbaren Eigenschaften dieses kontroversen Malers müssen allerdings aus dem Zeitgeist gedeutet, und unter dem Begriff "Maler der Empfindsamkeit" verständlich gemacht werden. Mildorfer umfassend zu bearbeiten ist ein Desideratum, denn ohne ihn als Verbindungsglied zwischen Paul Troger, seinem Lehrer und Franz Anton Maulbertsch, seinem Schüler voll zu erfassen, wird immer ein Baustein im Gefüge der österreichischen Barockmalerei fehlen

Josef Ignaz Mildorfer 1719-1775

This monograph on Joseph Ignaz Mildorfer (1719-1775) consists of forteen chapters, that after having given an overall curriculum, depict the various stations in the painter's working process. Special emphasis has been given to such criteria as the socio-economic, political and esthetic impacts, that shaped the development of this intriguing artist. Mildorfer was born into a distinguished family of painters in Innsbruck, where he was taught the basics of his profession. However, he was also exposed to the newly imported paintings from southern Germany, which at this time sparked Tyrolian tradition with international flavor. Partly due to those early stimuli, the young painter managed to instantly gain the renowned "big prize" of the Academy, upon his arrival in Imperial Vienna. This distinction was a prerequisite to any further career. Praised by his contemporaries as the most prodigious pupil of Paul Troger, Mildorfer soon was offered remarkable employments. His first major task, the complete decoration of the pilgrimage church at Hafnerberg near Vienna, comprising works in fresco and oil was soon to be followed by a commission from the Imperial court. But Austria was plagued by a raging War of Succession, which cast its shadow upon the job market, forcing Mildorfer to venture out into alternative fields. This he found in the painting of battlescenes. In this genre the young artist produced works of such rebellious intenseness that surpassed all his colleagues' endeavors and saved him a special niche. It might well be that those particular paintings drew the attention of the last great sponsers of the monarchy to Mildorfer, resulting in his being appointed painter of the court to the Duchess of Savoy, neé Maria Theresia Princess of Liechtenstein. (By way of scholarly work in the Princely Archives of Liechtenstein we have now established answers to questions regarding character and extend of Mildorfers work for the Duchess, that up till now has been obscured). In addition this period marked the beginning of a long lasting relationship with various branches of the Esterházy family, culminating in Mildorfer's appointment to Esterháza. Here he was commissioned to paint al fresco in Duke Nikolaus Esterházy's castle, one of the last manifestations of feudal style, the elaborate adornment of which promted the Duke with the attribute "The Magnificent". When Mildorfer was elected Professor at the Academy (kaiserlich-königliche Hofakademie der Mahler, Bildhauer und Baukunst) this not only marked the zenith of his career but also had major impact on one of the most thrilling phenomena within eighteenth century Viennese art. It was under his leadership that a movement took center stage, that was aprostophized the "Einheitsstil der Wiener Akademie". Carried out by an array of his scholars, notably Franz Anton Maubertsch this faszinating manifestation had Mildorfer's ideas at its core. With his contributions in the Crown Lands of the Habsburg monarchy in mind, his work makes him a typical Central-European artist of the eighteenth century. However some of his lesser graspable traits can only be understood out of the "Zeitgeist" and must be explained under the term of "painter of the sensibility". Since Mildorfer is the link between Paul Troger, his teacher and Franz Anton Maulbertsch, his student, a comprehensive biography of this artist is an absolute must. Only that makes a profound understanding of the third generation of Austrian barock-painting possible

Das Spielzeug fährt auf Urlaub : Spielzeugfreier Kindergarten - eine exemplarische Studie zu Aspekten des Spiels von Kindergartenkindern

Im Vordergrund dieses Beitrages steht das Projekt Spielzeugfreier Kindergarten. Dabei wird für zirka drei Monate das gesamte vorgefertigte Spielmaterial, welches in der Betreuungs- und Bildungseinrichtung vorhanden ist, weggeräumt. Obwohl das Projekt aus der Suchtprävention stammt, erscheint es aus elementarpädagogischer Sicht ebenfalls interessant, da das freie Spiel der Kinder analysiert werden kann. Mithilfe einer nicht-teilnehmenden Beobachtung soll geklärt werden, wie sich drei vorab festgelegte Aspekte des kindlichen Spiels die Spiel-, Interaktionsformen und die Engagiertheit während der Zeit ohne Spielzeug gestalten. Zudem wurde ein Blick auf die Zeit vor und nach dem Projekt geworfen. Das empirische Material wurde mit einem Beobachtungsbogen erhoben und anschließend deskriptiv ausgewertet. Insgesamt wurden zwölf Kinder im Alter zwischen drei und fünf Jahren in zwei projektdurchführenden Kindergärten beobachtet. Die Ergebnisse zeigen, dass während der spielzeugfreien Zeit bestimmte Spiel- und Interaktionsformen im Vordergrund stehen und es zu engagierten Spielen kommt.This paper is based upon the project „Spielzeugfreier Kindergarten” (i.e. kindergarten without toys). All the regular, „prefabricated” toys that are usually available in the childcare centre, are removed for about three months. Although the idea of the project originates in addiction prevention, it is also interesting from an elementary pedagogy point of view, since the free play of the children can be analysed. The study covers by using a non-participating observation how three predefined aspects of the child's play the play forms, the interaction forms and the involvement affect their time without toys. In addition, the time frames before and after the project are covered in this paper. The empirical material was collected by using observation sheets and analysed descriptively afterwards. A total of twelve children between the ages of three and five were observed in two kindergartens. The results show that during the toy-free time specific play forms and interaction forms are dominant and the children are involved in their games.vorgelegt von Elisabeth Ch. Payer, BA ; Mailina Petritsch, BAZusammenfassungen in Deutsch und EnglischAbweichender Titel laut Übersetzung der VerfasserinnenKarl-Franzens-Universität Graz, Masterarbeit, 2016(VLID)163159