Effects of Progesterone and Its Antagonist Mifepristone on Progesterone Receptor A Expression in Human Umbilical Vein Endothelial Cells

Effects of female steroid hormones on endothelial cells are gaining increased importance due to several studies on the effects of hormonal treatment on cardiovascular risk. Recent data argue for an improvement of endothelium-derived relaxation and impaired vascular contraction by estradiol, whereas progesterone and testosterone might entail contrary effects. So far, gestagenic influence on endothelial cell physiology is poorly understood. Human umbilical vein endothelial cells (HUVECs) exposed to the female sex hormones estradiol and progesterone show expression of estrogen receptor-beta (ER beta) and progesterone receptor A (PR-A), and are negative for ER alpha and PR-B. The aim of this study was to analyze the expression and stimulation of PR-A and -B in HUVECs after stimulation with progesterone and PR antagonists that are commercially available. PR-B expression or upregulation was abrogated after application of progesterone or antagonists to HUVECs. Expression of PR-A could be significantly upregulated with progesterone and mifepristone. Unexpectedly, stimulation with the progesterone antagonist RU486 (mifepristone) was accomplished by an upregulation of PR-A expression in our study. We conclude that gestagenic effects on HUVECs independent of modulators are mediated via the PR-A. Copyright (C) 2009 S. Karger AG, Base

Evaluation of a Novel Anti-Mucin 1 (MUC1) Antibody (PankoMab) as a Potential Diagnostic Tool in Human Ductal Breast Cancer; Comparison with Two Established Antibodies

Aim: PankoMab is a novel antibody that recognizes a tumor-specific epitope of Mucin 1 (MUC1). The aim of this study was the evaluation of PankoMab as a potential diagnostic tool and its comparison with two established antibodies against MUC1 in human ductal breast cancer. Materials and Methods: Breast carcinomas were obtained from 82 patients. MUC1 expression and hormone receptor status were determined by immunohistochemistry of paraffin-embedded material. Results: PankoMab revealed strong correlation to hormone receptor expression. DF3 showed no correlation with grading, lymph node involvement and/or estrogen receptor (ER) expression. In the subgroup of lymph node-positive and ER-negative tumors, we saw a significantly reduced DF3 staining in G3 tumors compared to G2 tumors. VU-4-H5 showed increased staining intensity in correlation with increased grading. In addition, we also identified a significantly higher expression of the VU-4-H5 epitope in lymph node-positive carcinomas compared to carcinomas without lymph node involvement. Conclusion: PankoMab revealed strong correlation to hormone receptor expression in ductal carcinoma of the breast. VU-4-H5 showed increased staining intensity in correlation with increased grading and lymph node involvement. PankoMab and VU-4-H5 staining could be a useful combination in ductal breast cancer prognosis by immunohistochemistry

Fremdsprachen berufsorientiert lernen und lehren: Kommunikative Anforderungen der Arbeitswelt und Konzepte für den Unterricht und die Lehrerausbildung am Beispiel des Deutschen als Fremdsprache

Ausgehend von den Wandlungsprozessen in der Arbeitswelt und einem daraus resultieren-den wachsenden Bedarf an Kommunikation in einer oder mehreren Fremdsprachen, unter-sucht die vorliegende Studie zunächst die grundlegenden qualitativen Anforderungen an die fremdsprachliche kommunikative Kompetenz der Beschäftigten in Unternehmen. Daraus werden Grundprinzipien und Planungsvariablen für einen berufsorientierten Fremdsprachen-unterricht abgeleitet, der die Lernenden nicht nur zur Bewältigung aktueller und künftiger fremdsprachlicher und interkultureller Anforderungen der Arbeitswelt befähigt, sondern sie auch in die Lage versetzt, sich den Wandlungsprozessen der Arbeitswelt und darüber hinaus der Gesellschaft anzupassen bzw. diese mitzugestalten. Die Orientierung des Fremdsprachenunterrichts an den Bedürfnissen von Lernenden, die gezielt eine auf berufliche Verwendungssituationen bezogene fremdsprachliche Handlungs-kompetenz aufbauen möchten, verlangt nach Lehrenden, die ein entsprechend bedarfsge-rechtes Unterrichtsangebot erstellen können. Die Studie untersucht deshalb, wie angesichts aktueller bildungswissenschaftlicher Diskussionen eine berufsorientierte Ausbildung konzi-piert sein muss, die die angehenden Lehrenden auf die Planung und Durchführung berufs-orientierten Fremdsprachenunterrichts in unterschiedlichen, schulischen und außerschuli-schen Bildungsbereichen vorbereitet. Ziel der Arbeit ist es, unter Einbeziehung der Diskussi-onen um Professionalisierung, Modularisierung und Bildungsqualität einerseits und den aus der Arbeitswelt, dem berufsorientierten Fremdsprachenunterricht und der berufsorientierten Lehrerausbildung resultierenden Anforderungen andererseits ein Modell für ein Studienprofil „Berufsorientierter Fremdsprachenunterricht“ am Beispiel des Deutschen als Fremdsprache (DaF) zu entwickeln, das flexibel in einen modularisierten Masterstudiengang integriert wer-den kann

Jenseits von Fachsprache? Eine Studie zur Kommunikation im Betrieb und ihre Implikationen für den berufsorientierten Fremdsprachenunterricht und die Materialgestaltung

Der Artikel fasst Ergebnisse einer Studie zur Kommunikation an Arbeitsplätzen in unterschiedlichen Branchen im Hinblick auf den mündlichen Gebrauch von Fachsprache zusammen. Es werden Konsequenzen für die Unterrichts- und Materialgestaltung im Bereich Deutsch als Fremdsprache abgeleitet und eine Reihe von Forschungsdesiderata zur mündlichen Kommunikation in der Arbeitswelt aufgezeigt

Oxidative stress stimulates alpha-tocopherol transfer protein in human trophoblast tumor cells BeWo

alpha-Tocopherol transfer protein (alpha-TTP) has been identified as the major intracellular transport protein for the antioxidant vitamin E (alpha-Tocopherol). Expression of alpha-TTP on the reproductive system has been described both in mouse uterus and lately in the human placenta. The aim of this study was to clarify if placental expression of alpha-TTP can be modified by substances causing oxidative reactions. The human choriocarcinoma cell line BeWo was, therefore, treated with two known pro-oxidants. alpha-TTP expression was determined with immunocytochemistry and evaluated by applying a semiquantitative score. The presence of pro-oxidants in BeWo cells induced alpha-TTP expression. We thus hypothesize that stimulation of alpha-TTP expression by oxidative stress, as this was induced by pro-oxidants, could be part of an antioxidant process occurring in the placenta in the aim of enhancing the supply of alpha-Tocopherol. This process could occur both in normal pregnancies, as well as in pregnancy disorders presented with intensified oxidative stress. In that view, this model is proposed for further oxidative stress studies on trophoblast and placenta, on the grounds of clarifying the role of alpha-Tocopherol in pregnancy physiology and pathophysiology

Tracer measurements in the tropical tropopause layer during the AMMA/SCOUT-O3 aircraft campaign

We present airborne in situ measurements made during the AMMA (African Monsoon Multidisciplinary Analysis)/SCOUT-O3 campaign between 31 July and 17 August 2006 on board the M55 Geophysica aircraft, based in Ouagadougou, Burkina Faso. CO2 and N2O were measured with the High Altitude Gas Analyzer (HAGAR), CO was measured with the Cryogenically Operated Laser Diode (COLD) instrument, and O3 with the Fast Ozone ANalyzer (FOZAN). We analyze the data obtained during five local flights to study the dominant transport processes controlling the tropical tropopause layer (TTL) above West-Africa: deep convection up to the level of main convective outflow, overshooting of deep convection, horizontal inmixing across the subtropical tropopause, and horizontal transport across the subtropical barrier. Except for the flight of 13 August, distinct minima in CO2 indicate convective outflow of boundary layer air in the TTL. The CO2 profiles show that the level of main convective outflow was mostly located between 350 and 360 K, and for 11 August reached up to 370 K. While the CO2 minima indicate quite significant convective influence, the O3 profiles suggest that the observed convective signatures were mostly not fresh, but of older origin. When compared with the mean O3 profile measured during a previous campaign over Darwin in November 2005, the O3 minimum at the main convective outflow level was less pronounced over Ouagadougou. Furthermore O3 mixing ratios were much higher throughout the whole TTL and, unlike over Darwin, rarely showed low values observed in the regional boundary layer. Signatures of irreversible mixing following overshooting of convective air were scarce in the tracer data. Some small signatures indicative of this process were found in CO2 profiles between 390 and 410 K during the flights of 4 and 8 August, and in CO data at 410 K on 7 August. However, the absence of expected corresponding signatures in other tracer data makes this evidence inconclusive, and overall there is little indication from the observations that overshooting convection has a profound impact on TTL composition during AMMA. We find the amount of photochemically aged air isentropically mixed into the TTL across the subtropical tropopause to be not significant. Using the N2O observations we estimate the fraction of aged extratropical stratospheric air in the TTL to be 0.0±0.1 up to 370 K during the local flights, increasing above this level to 0.2±0.15 at 390 K. The subtropical barrier, as indicated by the slope of the correlation between N2O and O3 between 415 and 490 K, does not appear as a sharp border between the tropics and extratropics, but rather as a gradual transition region between 10 and 25° N latitude where isentropic mixing between these two regions may occur

Enabling the discovery of thematically related research objects with systematic spatializations

It is challenging for scholars to discover thematically related research in a multidisciplinary setting, such as that of a university library. In this work, we use spatialization techniques to convey the relatedness of research themes without requiring scholars to have specific knowledge of disciplinary search terminology. We approach this task conceptually by revisiting existing spatialization techniques and reframing them in terms of core concepts of spatial information, highlighting their different capacities. To apply our design, we spatialize masters and doctoral theses (two kinds of research objects available through a university library repository) using topic modeling to assign a relatively small number of research topics to the objects. We discuss and implement two distinct spaces for exploration: a field view of research topics and a network view of research objects. We find that each space enables distinct visual perceptions and questions about the relatedness of research themes. A field view enables questions about the distribution of research objects in the topic space, while a network view enables questions about connections between research objects or about their centrality. Our work contributes to spatialization theory a systematic choice of spaces informed by core concepts of spatial information. Its application to the design of library discovery tools offers two distinct and intuitive ways to gain insights into the thematic relatedness of research objects, regardless of the disciplinary terms used to describe them

Update on the role of antipsychotics in the treatment of Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood and characterized by chronic occurrence of motor and vocal tics. The disorder can lead to serious impairments of both quality of life and psychosocial functioning, particularly for those individuals displaying complex tics. In such patients, drug treatment is recommended. The pathophysiology of TS is thought to involve a dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. Congruently, dopamine receptor antagonism of neuroleptics appears to be the most efficacious approach for pharmacological intervention. To assess the efficacy of the different neuroleptics available, a systematic, keyword-related search in PubMed (National Library of Medicine, Washington, DC) was undertaken. Much information on the use of antipsychotics in the treatment of TS is based on older data. Our objective was to give an update and therefore we focused on papers published in the last decade (between 2001 and 2011). Accordingly, the present review aims to summarize the current and evidence-based knowledge on the risk-benefit ratio of both first and second generation neuroleptics in TS

Subclinical infection of macaques and baboons with a baboon simarterivirus

Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies