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Na I.-K.,Charite - Medical University of Berlin | Na I.-K.,Institute of Medical Immunology | Na I.-K.,Experimental and Clinical Research Center | Wittenbecher F.,Charite - Medical University of Berlin | And 12 more authors.
Haematologica | Year: 2013

Rabbit antithymocyte globulin-Genzyme™ is used to prevent graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Common disadvantages of treatment are infectious complications. The effects of rabbit antithymocyte globulin-Genzyme™ on thymic function have not been well-studied. Multicolor flow cytometry was used to analyze the kinetics of conventional and regulatory T cells in adult patients treated (n=12) or not treated (n=8) with rabbit antithymocyte globulin-Genzyme™ during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme™ had almost undetectable levels of recent thymic emigrants (CD45RA+CD31+) of both conventional and regulatory CD4 T cells throughout the 6 months after allogeneic hematopoietic stem cell transplantation whereas CD4+CD45RAmemory T cells were less affected, but their levels were also significantly lower than in patients not treated with rabbit antithymocyte globulin-Genzyme™. In vitro, rabbit antithymocyte globulin-Genzyme™ induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-FreseniusTM. Rabbit antithymocyte globulin-Genzyme™ in combination with a conditioning regimen strongly impairs thymic recovery of both conventional and regulatory CD4+ T cells. The sustained depletion of conventional and regulatory CD4+ T cells carries a high risk of both infections and graft-versus-host disease. Our data indicate that patients treated with rabbit antithymocyte globulin-Genzyme™ could benefit from thymus-protective therapies and that trials comparing this product with other rabbit antithymocyte globulin preparations or lymphocyte-depleting compounds would be informative. ©2013 Ferrata Storti Foundation. Source


John L.,Infectiology and Rheumatology | Aguilar I.,National University of Costa Rica | Ayasse M.,University of Ulm | Jarau S.,University of Ulm
Insectes Sociaux | Year: 2012

Social insects have evolved highly developed communication systems, enabling them to coordinate complex interactions in their colonies. Pheromones play a major role in the coordination of many tasks. In Trigona corvina, a stingless bee that occurs in Central America, foragers use pheromones produced in their labial glands to scent mark solid substrates between a food source and their nest. Newly recruited bees subsequently follow these scent marks until they reach the food source. A recent study has revealed nest-specific differences in the composition of these trail pheromones in colonies of T. corvina, suggesting that pheromone specificity may serve to avoid competition between foragers from different nests. However, the nests used in this study came from different populations and their foragers certainly never met in the field (Jarau et al., 2010). The aim of the present study was to investigate whether differences in the trail pheromones of foragers from different nests can also be found between neighbouring colonies within populations. We analysed the composition of trail pheromones from labial gland secretions extracted from workers from nine colonies collected at three different populations in Costa Rica. The differences in pheromone composition were even more distinct between neighbouring nests within a population than between nests of different populations. This finding corroborates the hypothesis that nest specificity of trail pheromones serves to communicate the location of a food source exclusively to nestmates, thereby avoiding intraspecific competition at resources. Resource partitioning by avoiding conspecific non-nestmates is particularly adaptive for aggressive bee species, such as T. corvina. © 2012 International Union for the Study of Social Insects (IUSSI). Source


Freise C.,Infectiology and Rheumatology | Trowitzsch-Kienast W.,Berlin Technical University of Applied Sciences | Ruehl M.,Infectiology and Rheumatology | Erben U.,Infectiology and Rheumatology | And 4 more authors.
Investigational New Drugs | Year: 2012

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Treatment options, especially in advanced tumor stages, are still limited. Inhibition of signaling cascades involved in the pathogenesis of HCC-such as NF-κB-offer a promising therapeutic approach. Aim of this study was to examine anti-neoplastic effects of (+)-episesamin which has been isolated from an anti-fibrotic extract of Lindera obtusiloba on human HCC cells with particular interest in activation of NF-κB. The human HCC cell lines HepG2, Huh-7 and SK-Hep1 were treated with (+)-episesamin. Beside measurement of proliferation, invasion and apoptosis, effects of (+)-episesamin on NF-κB-activity, VEGF secretion and enzymatic MMP-9 activity were determined. Anti-inflammatory effects were assessed by IL-6 ELISA using HCC cells and RAW264.7 macrophages. 10 μM (+)-episesamin reduced the proliferation of HCC cells by ∼50%, suppressed invasion and induced apoptosis. DNA-binding ELISA experiments revealed that (+)-episesamin treated HCC cells showed a suppressed basal and TNFα-induced activation of NF-κB and a subsequent suppression of TNFα-and LPS-induced IL-6 production. Further, (+)-episesamin exhibited inhibitory effects on the enzymatic activity of recombinant MMP-9 and the secretion of MMP-9 and VEGF by HCC cells into their supernatants. Our findings show that anti-neoplastic effects of (+)-episesamin are mediated via suppressed activation of NF-κB which entails a decreased release of proinflammatory IL-6. In addition, (+)-episesamin inhibits MMP-9, which is strongly expressed in invasive HCC, and the production of proangiogenic VEGF. We conclude that (+)-episesamin has the potential to be further explored as a complementary treatment for HCC. © 2012 Springer Science+Business Media, LLC. Source


Braum L.S.,Charite Medical School | McGonagle D.,University of Leeds | Bruns A.,Charite Medical School | Philipp S.,Psoriasis Study Center | And 6 more authors.
European Radiology | Year: 2013

Objective: To test the hypothesis that microanatomical differences in joint disease localisation could be exploited using high-resolution MRI to better differentiate among rheumatoid arthritis (RA), spondyloarthritis/psoriatic arthritis (SpA/PsA) and osteoarthritis (OA) in clinical practice. Methods: Sixty-nine patients with suspected inflammatory joint disease of the hand or feet underwent high-resolution MRI using a small loop coil. Images were scored blinded to the clinical status. Various joint changes like periostitis, osteitis, erosions, enthesitis and synovitis were recorded. The image-based diagnosis was compared with the clinical diagnosis. Results: In 59.4 % of the patients the clinical diagnosis was confirmed on image analysis. This was high for OA (80 %), moderately good for RA (67 %) but only 50 % for SpA/PsA. The major difficulty was to distinguish OA from SpA/PsA where common imaging findings are evident including periostitis (SpA/PsA 45 %, OA 40 % compared with RA 0 %; P = 0.015). Likewise, osteitis was frequently detected in SpA/PsA (79 %) and OA (80 %) and less frequently in RA (42 %) (P = 0.014). Conclusion: Characterisation of inflammatory disorders of small joints merely using high-resolution MRI remains challenging especially in the differentiation between OA and PsA. These findings are likely explained by common microanatomical similarities in disease expression rather than limitations of imaging techniques. Key Points: • High-resolution MRI is increasingly used to investigate joint disease. • Osteitis and periostitis occur in psoriatic and osteoarthritis (but not rheumatoid arthritis). • In severely affected patients the amount of synovitis and erosions is similar. © 2013 European Society of Radiology. Source


Bichev D.,Charite - Medical University of Berlin | Treese C.,Infectiology and Rheumatology | Von Winterfeld M.,Charite - Medical University of Berlin | Breithaupt K.,Charite - Medical University of Berlin | And 4 more authors.
Oncology (Switzerland) | Year: 2015

Background: Perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (5-FU) (ECF)-like regimens is the European standard for patients with adenocarcinoma of the gastroesophageal junction (GEJ) or gastric body (GaCa) stage UICC II/III (staged according to the Union for International Cancer Control). However, limited data exist on the histopathological response and relevance of prognosis for patients homogeneously treated with ECF(-like) therapies. Methods: All patients with GEJ/GaCa treated from September 2004 to September 2008 by perioperative ECF(-like) chemotherapy were retrospectively analyzed. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine when indicated. The histopathological response was assessed using the Becker score. Results: Seventy-seven patients were analyzed with a median follow-up of 72.3 months. R0 resection was achieved in 53 of 68 operated patients. Recurrence was observed in 25 (32.5%) of these curatively treated patients, whereas 53/77 patients (68.8%) died, 39 (50.6%) of whom tumor related. The 5-year overall survival (OS) for the intention-to-treat population was 36.3%, and the 5-year tumor-specific survival was 42.2%. Pathological complete response (pCR) was seen in 10 patients (13.0%) and near pCR in 3 patients (3.9%). Patients with pCR had a significantly prolonged 5-year OS of 80.0 versus 29.7% compared to the nonhistopathological complete remission group (p = 0.01). Conclusion: In our retrospective analysis, ECF(-like) pretreatment resulted in a (near) pCR rate of 16.9%. In line with other regimens, our data suggest that histopathological response predicts the OS in patients treated with ECF(-like) regimens. © 2015 S. Karger AG, Basel. Source

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