All for One and One for All: Herpesviral MicroRNAs Close in on Their Prey

Herpesviruses subvert immune cell activation by inhibiting NK cell receptor (NKG2D)-activating ligands such as MICB. A human cytomegalovirus microRNA was recently shown to repress MICB expression. Nachmani et al. (2009) extend this finding to two other human herpesviruses, providing evidence for a conserved functional role of viral microRNAs despite no sequence conservation among them

Разработка информационной системыучета и анализа деятельности автошколы "Академия вождения"

New challenges result from the virtualization and distribution of product development activities. This article analyzes problems of cooperative engineering as well as methods and tools for the virtual engineering of extended products. Based on these analyses, a broad road map is proposed that articulates public- and civil-sector roles in coping with future engineering challenges. With a strategic horizon, the public-sector role targets the creation of a knowledge-intensive global business ecosystem conducive to balanced civil-sector innovation and sustainable growth. The civil-sector roles evolve tactics that implement proven cooperative and virtual engineering practices with a focus on value creation

Subsidiarität und Institutionenökonomik Zu einer sozialtheoretischen und –ethischen Präzisierung des Subsidiaritätsprinzips

Welche Ansätze der Sozialtheorie tragen zu einer Präzisierung der Anwendung des Subsidiaritätsprinzips bei? Neben verschiedenen soziologischen Theorien, aufgefasst als a priori holistische Methoden, wird der methodologisch-individualistische Ansatz der Institutionenökonomik angewendet – unter Einbeziehung des aktuellen Standards der modernen Moraltheologie, wie er sich bei Bruno Schüller findet. Von letzterem her zeigt sich, dass das Subsidiaritätsprinzip generell erkundet, welche gesellschaftliche Einheit zur Lösung eines sozialen Problems am effizientesten erscheint. Aus der Perspektive der Institutionenökonomik, hier insbesondere der Konzeption von Institutionen als produktivem Reflex auf Gefangenendilemmastrukturen, wird das Prinzip zum einen von gesellschaftlichen Einheiten auf alle Arten von Institutionen erweitert, zum anderen als sein Kriterium formuliert, eine Institution solle etabliert werden, wenn ihr Nutzen – aufgefasst in einem weiten Sinn jeglicher Erweiterung des Handlungs- und Freiheitsraumes der Einzelmenschen – ihre sozialen Kosten übersteigt. Damit erweist sich die Schaffung neuer, problemlösender Institutionen als ethisch und ökonomisch vorteilhaft.Which approaches of social theory contribute to a more precise application of the subsidiary principle? Besides various theories of sociology, understood as a priori holistic methods, the methodologically individualistic approach of institutional economics – also involving the standard of modern moral theology as found at Bruno Schüller – is applied. From the latter, it is evident, that the subsidiary principle generally explores, which societal unit is most efficient to solve a social problem. From the perspective of institutional economics, especially the conception of institutions as a productive reflex on prisoner dilemmas, the principle on the one hand is widened from societal units to all sorts of institutions, on the other as its criteria is formulated, an institution should be implemented, if its benefit – understood in a wide sense of enlarging the space of acting and liberty of the single man – exceeds its social costs. Thus the creation of new, problem solving institutions shows itself as ethically and economically advantageous

Solidarität als Positivsummenspiel. Sozialstaatsbegründung in der Perspektive der Neuen Intstitutionenökonomik

Klassische Sozialethik und Neue Institutionenökonomik lassen sich in ihrem Verständnis von Solidarität anhand der Paradigmata des Null- bzw. Positivsummenspiels unterscheiden. Da das Positiv- das Nullsummenspiel dem Umfang nach umfassen kann, liegt die Überlegung nahe, dass die Neue Institutionenökonomik dem Umfang nach den Sozialstaat mindestens so weit begründen kann wie die Christliche Sozialethik. Ökonomie ist damit nicht per se auf Sozialabbau angelegt. Der ökonomische Ansatz interpretiert Moral, Sozialstaat und Sozialversicherung als Institutionen zur Ermöglichung von Kooperationschancen zum wechselseitigen Vorteil. Der Sozialstaat kann verallgemeinert als eine Sozialversicherung aufgefasst werden, die Menschen risikoreicheres und damit produktiveres Handeln ermöglicht. Institutionen der sozialen Sicherung sind solange zu etablieren, wie ihre Kosten unter dem wechselseitigen Nutzen der durch sie realisierten Kooperationschancen für die Gesellschaftsmitglieder liegen. Die Betrachtung der Neuen Institutionenökonomik zeigt weiterhin, dass sich Teilfunktionen von Solidarität in konkreten Sozialversicherungssystemen differenzieren lassen. Daraus lassen sich Empfehlungen zu einer auch sozial effizienteren Rekombination dieser Teilfunktionen bei Reformen ableiten. Generell gilt, dass im Sektor der sozialen Sicherung ebenso wie auf dem Gesamt der Märkte für materielle Güter Wettbewerbselemente so etabliert werden können, dass sie auf einer vorgelagerten Ebene als Kooperation zum wechselseitigen Vorteil verstanden und auf der nachgelagerten Ebene auch so gestaltet werden können. Die normative Ambivalenz der im Wettbewerb begegnenden Dilemmastrukturen muss dazu allerdings durch geeignete Rahmenbedingungen zielgerichtet etabliert werden

5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis

<p>Abstract</p> <p>Background</p> <p>Non-small cell lung cancer (NSCLC) is one of the most frequent malignancies and has a high mortality rate due to late detection and lack of efficient treatments. Identifying novel drug targets for this indication may open the way for new treatment strategies. Comparison of gene expression profiles of NSCLC and normal adjacent tissue (NAT) allowed to determine that 5-alpha-reductase type I (SRD5A1) was up-regulated in NSCLC compared to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation and survival of NSCLC.</p> <p>Methods</p> <p>siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer cell lines in order to determine the impact on proliferation, on distribution during the different phases of the cell cycle, and on apoptosis/necrosis. In addition, lung cancer cell lines were treated with 4-azasteroids, which specifically inhibit SRD5A1 activity, and the effects on proliferation were measured. Statistical analyses using ANOVA and post-hoc Tamhane-T2-test were performed. In the case of non-parametric data, the Kruskal-Wallis test and the post-hoc Mann-Whitney-U-test were used.</p> <p>Results</p> <p>The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts being reduced to 10% of control levels. Knock-down efficiency was furthermore confirmed at the protein level. However, no effect of SRD5A1 silencing was observed in the proliferation assay, the cell cycle analysis, and the apoptosis/necrosis assay. Treatment of lung cancer cell lines with 4-azasteroids did not significantly inhibit proliferation.</p> <p>Conclusions</p> <p>In summary, the results suggest that SRD5A1 is not a crucial enzyme for the sustained proliferation of NSCLC cell lines.</p

Severe Disseminated Coagulopathy Caused by Adenocarcinoma with Bone Marrow Metastasis

Background: Patients with mucin-producing adenocarcinoma have an increased risk for venous and arterial thrombosis. When these patients present with thrombocytopenia, disseminated intravascular coagulopathy (DIC) is often the underlying cause. Case Report: We report 2 patients who were admitted due to bleeding symptoms of unknown cause, in whom further workup revealed adenocarcinoma-induced DIC. Conclusion: In elderly patients presenting with signs of DIC, such as reduced fibrinogen levels, elevated prothrombin time, elevated D-dimer, and thrombocytopenia, without any obvious reason (e.g., sepsis), adenocarcinoma-associated coagulopathy should be considered as the underlying cause. Paradoxically, in these patients bleeding symptoms improve when the patient is sufficiently anti-coagulated with low molecular weight heparin. Treatment of the underlying disease is of central importance in controlling acute or chronic DIC associated with malignant diseases and chemotherapy should be started as soon as possible

Die Lactatdehydrogenase-Isoenzymmuster des Myokards und Reizleitungssystems des Kalbsherzens

Peer Reviewe

Mucositis after Reduced Intensity Conditioning and Allogeneic Stem Cell Transplantation

Background: Therapyrelated mucositis is associated with considerable morbidity. This complication following allogeneic stem cell therapy (alloSCT) is less severe after reduced intense conditioning (RIC); however, even here it may be serious. Methods: 52 patients (male: n = 35 (67%), female: n = 17 (33%)) at a median age of 62 years (35–73 years) underwent alloSCT after RIC. Conditioning was either total body irradiation (TBI)2Gy/±fludarabine (n = 33, 63.5%) or chemotherapy based. Graftversushost disease (GvHD) prophylaxis was carried out with cyclosporine A ± mycophenolate mofetil (MMF). 45 patients (87%) received shortcourse methotrexate (MTX). Mucositis was graded according to the Bearman and the World Health Organisation (WHO) scale. A variety of parameters were correlated with mucositis. Results: The Bearman and WHO scales showed excellent correlation. Mucositis was significantly more severe after chemotherapybased conditioning compared to conditioning with TBI2Gy/±fludarabine (p < 0.002) as well as in cases with an increase in creatinine levels above the upper normal value (UNV) on day +1 after SCT (p < 0.05). Furthermore, the severity correlated with time to engraftment of leucocytes (correlation coefficient (cc) = 0.26, p < 0.02) and thrombocytes (cc = 0.38, p < 0.001). Conclusions: The conditioning regimen and increased creatinine levels at day +1 were identified as factors predicting the severity of mucositis after RICSCT. Creatinine levels on day +1 after SCT may help identify patients at risk for severe mucositis in the further course of transplantation

Aminoglycoside-free interventional antibiotic management in patients undergoing haemopoietic stem cell transplantation

The position of aminoglycosides within interventional antibiosis in the early phase after stem cell transplantation has not been fully clarified so far although their use can induce serious renal impairment. To investigate this question early-infection data from 152 patients undergoing 195 allogeneic and autologous stem cell transplantations were investigated. Prophylaxis and treatment of infections followed international standards; however, aminoglycosides were omitted to avoid additional risks such as ototoxicity and nephrotoxicity and increased selection of resistant pathogens. Costs were another aspect

Intensive Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation During a 10-Year Period in 64 Patients with Germ Cell Tumor

AbstractDespite gratifying cure rates in germ cell tumors, conventional-dose chemotherapy achieves long-term remissions in less than 50% of patients at high risk. High-dose chemotherapy followed by autologous (auto) peripheral blood stem cell transplantation (PBSCT) has shown impressive remission rates in high-risk and relapsed germ cell tumors. We report on 64 consecutive patients with high- (n = 39), intermediate- (n = 18), and refractory or relapsed low- (n = 7) risk germ cell tumors who underwent auto-PBSCT between January 1993 and February 2003. PBSCTs were performed as a single (n = 40) or repeated (n = 24) transplantation using either etoposide, ifosfamide, and carboplatin (n = 80) or related protocols (paclitaxel, ifosfamide, carboplatin, etoposide [n = 7]; carboplatin, etoposide, thiotepa [n = 4]). With a median follow-up of 6 years, estimated 2- and 5-year overall survivals were 77.2% (95% confidence interval [CI] 66.7-87.7) and 73.1% (95% CI 61.7-84.5), respectively. We observed unfavorable results in those patients showing refractoriness to cisplatin (hazard ratio 20.36; 95% CI 6.64-62.47) or no response to induction chemotherapy (hazard ratio 10.67; 95% CI 1.37-83.37). Auto-PBSCT was well tolerated, showed objective antitumor activity, and achieved long-term survival in patients at high risk and with relapse. Our data suggest that auto-PBSCT can increase response rates and may improve the outcome in these patients