Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Microbial Lipopeptides Induce the Production of IL-17 in Th Cells

Abstract: Naive Th cells can be directed in vitro to develop into Th1 or Th2 cells by IL-12 or IL-4, respectively. In vivo, chronic immune reactions lead to polarized Th cytokine patterns. We found earlier that Borrelia burgdorferi , the spirochaete that causes Lyme disease, induces Th1 development in αβ TCR-transgenic Th cells. Here, we used TCR-transgenic Th cells and oligonucleotide arrays to analyze the differences between Th1 cells induced by IL-12 vs those induced by B. burgdorferi . Transgenic Th cells primed with peptide in the presence of B. burgdorferi expressed several mRNAs, including the mRNA encoding IL-17, at significantly higher levels than Th cells primed with peptide and IL-12. Cytometric single-cell analysis of Th cell cytokine production revealed that IL-17 cannot be categorized as either Th1 or Th2 cytokine. Instead, almost all IL-17-producing Th cells simultaneously produced TNF-α and most IL-17 + Th cells also produced GM-CSF. This pattern was also observed in humans. Th cells from synovial fluid of patients with Lyme arthritis coexpressed IL-17 and TNF-α upon polyclonal stimulation. The induction of IL-17 production in Th cells is not restricted to B. burgdorferi . Priming of TCR-transgenic Th cells in the presence of mycobacterial lysates also induced IL-17/TNF-α coproduction. The physiological stimulus for IL-17 production was hitherto unknown. We show here for the first time that microbial stimuli induce the expression of IL-17 together with TNF-α in both murine and human T cells. Chronic IL-17 expression induced by microbes could be an important mediator of infection-induced immunopathology.

The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours

Abstract: Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with high affinity and specificity receptors overexpressed on tumours. PRRNT employing the radiotagged somatostatin receptor agonists 90Y-DOTATOC ([90Y-DOTA0,Tyr3]-octreotide) or 177Lu-DOTATATE ([177Lu-DOTA0,Tyr3,Thr8]-octreotide or [177Lu-DOTA0,Tyr3]-octreotate) have been successfully used for the past 15 years to target metastatic or inoperable neuroendocrine tumours expressing the somatostatin receptor subtype 2. Accumulated evidence from clinical experience indicates that these tumours can be subjected to a high absorbed dose which leads to partial or complete objective responses in up to 30 % of treated patients. Survival analyses indicate that patients presenting with high tumour receptor expression at study entry and receiving 177Lu-DOTATATE or 90Y-DOTATOC treatment show significantly higher objective responses, leading to longer survival and improved quality of life. Side effects of PRRNT are typically seen in the kidneys and bone marrow. These, however, are usually mild provided adequate protective measures are undertaken. Despite the large body of evidence regarding efficacy and clinical safety, PRRNT is still considered an investigational treatment and its implementation must comply with national legislation, and ethical guidelines concerning human therapeutic investigations. This guidance was formulated based on recent literature and leading experts’ opinions. It covers the rationale, indications and contraindications for PRRNT, assessment of treatment response and patient follow-up. This document is aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRNT and to deliver the treatment in a safe and effective manner. This document is largely based on the book published through a joint international effort under the auspices of the Nuclear Medicine Section of the International Atomic Energy Agency.

Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma

Abstract: Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.

Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).

Abstract: Objective To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). Methods One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. Results The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of ≥2.5 at baseline, 68% of infliximab-treated patients achieved improvement of ≥75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. Conclusion Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.

Boosting bit rates in noninvasive EEG single-trial classifications by feature combination and multiclass paradigms

Abstract: Noninvasive electroencephalogram (EEG) recordings provide for easy and safe access to human neocortical processes which can be exploited for a brain-computer interface (BCI). At present, however, the use of BCIs is severely limited by low bit-transfer rates. We systematically analyze and develop two recent concepts, both capable of enhancing the information gain from multichannel scalp EEG recordings: 1) the combination of classifiers, each specifically tailored for different physiological phenomena, e.g., slow cortical potential shifts, such as the premovement Bereitschaftspotential or differences in spatio-spectral distributions of brain activity (i.e., focal event-related desynchronizations) and 2) behavioral paradigms inducing the subjects to generate one out of several brain states (multiclass approach) which all bare a distinctive spatio-temporal signature well discriminable in the standard scalp EEG. We derive information-theoretic predictions and demonstrate their relevance in experimental data. We will show that a suitably arranged interaction between these concepts can significantly boost BCI performances.