Refine
Year of publication
- 2011 (124) (remove)
Document Type
- Article (124) (remove)
Has Fulltext
- yes (124)
Is part of the Bibliography
- no (124)
Keywords
- mitochondria (3)
- Hepatocellular carcinoma (2)
- Outcomes (2)
- TRAIL (2)
- Transarterial chemoembolization (2)
- apoptosis (2)
- chemotherapy (2)
- ADAM-17 (1)
- Actaea cimicifuga (1)
- Allochromatium vinosum (1)
- Alzheimer's disease (1)
- Alzheimer’s disease (1)
- Antiangiogenesis (1)
- Antiviral therapy (1)
- Aortic Valve Replacement (1)
- Attention (1)
- Autism (1)
- BCR/ABL (1)
- Black cohosh (1)
- Black cohosh induced liver injury (1)
- Bottom-up (1)
- C-clamp (1)
- CYP450 (1)
- Capsule endoscopy (1)
- Cell Adhesion (1)
- Clinical Skills (1)
- Competencies (1)
- Consensus methods (1)
- CoxVa (1)
- Crohn’s disease (1)
- Crossmodal (1)
- Cyclosporin A (1)
- Cytokines Induction (1)
- Delphi Survey (1)
- Delphie-Befragung (1)
- Directly acting antiviral agent (1)
- Drug induced liver injury (1)
- E-Learning (1)
- EET (1)
- EZ-IO® needle driver (1)
- Electroencephalography (1)
- Emergency medicine (1)
- Evaluation (1)
- Event-related potential (1)
- Fertigkeiten (1)
- Functional connectivity (1)
- Functional magnetic resonance imaging (1)
- Gene Regulation (1)
- Generalized procrustes analysis (1)
- Genome-wide association study (1)
- Genomic medicine (1)
- H1N1 (1)
- HSCT (1)
- Hemagglutination inhibition assay (1)
- Hepatitis C virus (1)
- Hepatotoxicity (1)
- Herb induced liver injury (1)
- Herbal hepatotoxicity (1)
- Highwire (1)
- Human genetics (1)
- Humangenetik (1)
- IAPs (1)
- Immunology (1)
- Immunosuppression (1)
- Independent component analysis (1)
- Individualized therapy (1)
- Inflammation (1)
- Inside-out Signaling (1)
- Integrin (1)
- Interferon-α (1)
- Interferon-λ, (1)
- Interleukin (1)
- Interleukin-22 (1)
- Intraosseous access (1)
- Klinische Fertigkeiten (1)
- Kompetenzen (1)
- Konsensus Methode (1)
- L2 (1)
- LFA-1 (1)
- Left Ventricular Mass (1)
- Lernziele (1)
- Local field potential (1)
- Lymphocyte (1)
- MCAK (1)
- MDM2 (1)
- MYCBP2 (1)
- Mgm1p (1)
- Multimedia (1)
- Multisensory (1)
- Multiset independent component analysis (1)
- Neuron (1)
- Object perception (1)
- Objectives (1)
- P600 (1)
- PAM (1)
- PHR1 (1)
- PI3K (1)
- Pain (1)
- Parkinson’s disease (1)
- Personal medicine (1)
- Phase-reset (1)
- Philadelphia Chromosome-positive leukemia (1)
- Podospora anserina (1)
- Portal (1)
- Practical skills (1)
- Praktische Fertigkeiten (1)
- Prospective randomized Analysis (1)
- Protein Translocation (1)
- SKAP1 (1)
- STDP (1)
- Schizophrenia (1)
- Sensory processing (1)
- Shunt (1)
- Single nucleotide polymorphism (1)
- Skills (1)
- Small bowel endoscopy (1)
- Sorafenib (1)
- T Cell Biology (1)
- T Cells (1)
- TIM23 (1)
- TKI (1)
- TRP Channels (1)
- TRPA1 (1)
- Thrombosis (1)
- Trafficking (1)
- Ubiquitin Ligase (1)
- Vision (1)
- acupuncture (1)
- adverse reaction (1)
- aging (1)
- anaemia (1)
- anoxygenic phototrophic sulfur bacteria (1)
- antibodies (1)
- asthma (1)
- auditory language processing (1)
- auto-structure (1)
- autovaccine (1)
- biomarker (1)
- blood transfusion (1)
- brainstem (1)
- cancer (1)
- chemoresistance (1)
- chinese medicine (1)
- chromosome instability (1)
- competitive peptide (1)
- dementia (1)
- dermatomes (1)
- dissimilatory sulfite reductase (1)
- drug resistance and invasiveness (1)
- dsr genes (1)
- e-Learning (1)
- evaluation (1)
- frontotemporal lobar degeneration (1)
- head zones (1)
- healthcare worker (1)
- hemorrhage (1)
- history of medicine (1)
- house dust mite allergy (1)
- human (1)
- hyperalgesia (1)
- i-AAA protease (1)
- image distortion (1)
- immunization (1)
- integrate and fire (1)
- kyphosis (1)
- lactate (1)
- medical education (1)
- medizinische Ausbildung (1)
- membrane protein (1)
- mitotic kinases (1)
- molecular targeted drugs (1)
- molecular targeting (1)
- multimedia (1)
- needle displacement (1)
- neurodegenerative diseases (1)
- nociceptors (1)
- non-Poissonian (1)
- novel H1N1 influenza (1)
- nutlin-3 (1)
- oligomerization (1)
- orthodeoxia (1)
- orthopaedic surgery (1)
- overreaching markers (1)
- p38 MAPK (1)
- p53 (1)
- pain (1)
- pancreatic cancer (1)
- patent foramen ovale (1)
- pathology (1)
- pelvic injury (1)
- pelvic packing (1)
- platypnea (1)
- preoperative assessment (1)
- preoperative preparation (1)
- prostate brachytherapy (1)
- proteasome inhibitor (1)
- protein quality control (1)
- racket sports (1)
- radiotherapy (1)
- referred pain (1)
- reflexes (1)
- regulation (1)
- sEH (1)
- safety (1)
- soluble tumor necrosis factor receptor (1)
- sox genes (1)
- speech segmentation (1)
- spike train (1)
- strength and conditioning mesocycle (1)
- sulfur globules (1)
- temperature (1)
- temporal correlations (1)
- thiosulfate oxidation (1)
- tolerability (1)
- toxicity (1)
- transcatheter closure (1)
- trochee (1)
- tumor necrosis factor converting enzyme (1)
- ultrasound (1)
- viscero-cutaneous (1)
Institute
- Medizin (124) (remove)
The E3 ubiquitin ligase MYCBP2 negatively regulates neuronal growth, synaptogenesis, and synaptic strength. More recently it was shown that MYCBP2 is also involved in receptor and ion channel internalization. We found that mice with a MYCBP2-deficiency in peripheral sensory neurons show prolonged thermal hyperalgesia. Loss of MYCBP2 constitutively activated p38 MAPK and increased expression of several proteins involved in receptor trafficking. Surprisingly, loss of MYCBP2 inhibited internalization of transient receptor potential vanilloid receptor 1 (TRPV1) and prevented desensitization of capsaicin-induced calcium increases. Lack of desensitization, TRPV internalization and prolonged hyperalgesia were reversed by inhibition of p38 MAPK. The effects were TRPV-specific, since neither mustard oil-induced desensitization nor behavioral responses to mechanical stimuli were affected. In summary, we show here for the first time that p38 MAPK activation can inhibit activity-induced ion channel internalization and that MYCBP2 regulates internalization of TRPV1 in peripheral sensory neurons as well as duration of thermal hyperalgesia through p38 MAPK.
Background: Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.
Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.
Methods: Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.
Results: 1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).
Conclusions: Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.
Trial Registration: clinicaltrials.gov, NCT00451412
Event-related potentials (ERPs) are widely used in basic neuroscience and in clinical diagnostic procedures. In contrast, neurophysiological insights from ERPs have been limited, as several different mechanisms lead to ERPs. Apart from stereotypically repeated responses (additive evoked responses), these mechanisms are asymmetric amplitude modulations and phase-resetting of ongoing oscillatory activity. Therefore, a method is needed that differentiates between these mechanisms and moreover quantifies the stability of a response. We propose a constrained subspace independent component analysis that exploits the multivariate information present in the all-to-all relationship of recordings over trials. Our method identifies additive evoked activity and quantifies its stability over trials. We evaluate identification performance for biologically plausible simulation data and two neurophysiological test cases: Local field potential (LFP) recordings from a visuo-motor-integration task in the awake behaving macaque and magnetoencephalography (MEG) recordings of steady-state visual evoked fields (SSVEFs). In the LFPs we find additive evoked response contributions in visual areas V2/4 but not in primary motor cortex A4, although visually triggered ERPs were also observed in area A4. MEG-SSVEFs were mainly created by additive evoked response contributions. Our results demonstrate that the identification of additive evoked response contributions is possible both in invasive and in non-invasive electrophysiological recordings.
IL-22 is an immunoregulatory cytokine displaying pathological functions in models of autoimmunity like experimental psoriasis. Understanding molecular mechanisms driving IL-22, together with knowledge on the capacity of current immunosuppressive drugs to target this process, may open an avenue to novel therapeutic options. Here, we sought to characterize regulation of human IL22 gene expression with focus on the established model of Jurkat T cells. Moreover, effects of the prototypic immunosuppressant cyclosporin A (CsA) were investigated. We report that IL-22 induction by TPA/A23187 (T/A) or αCD3 is inhibited by CsA or related FK506. Similar data were obtained with peripheral blood mononuclear cells or purified CD3(+) T cells. IL22 promoter analysis (-1074 to +156 bp) revealed a role of an NF-AT (-95/-91 nt) and a CREB (-194/-190 nt) binding site for gene induction. Indeed, binding of CREB and NF-ATc2, but not c-Rel, under the influence of T/A to those elements could be proven by ChIP. Because CsA has the capability to impair IκB kinase (IKK) complex activation, the IKKα/β inhibitor IKKVII was evaluated. IKKVII likewise reduced IL-22 induction in Jurkat cells and peripheral blood mononuclear cells. Interestingly, transfection of Jurkat cells with siRNA directed against IKKα impaired IL22 gene expression. Data presented suggest that NF-AT, CREB, and IKKα contribute to rapid IL22 gene induction. In particular the crucial role of NF-AT detected herein may form the basis of direct action of CsA on IL-22 expression by T cells, which may contribute to therapeutic efficacy of the drug in autoimmunity.
Recent genome-wide association studies (GWAS) have identified genetic variations near the IL28B gene which are strongly associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. Protective IL28B variations are strongly associated with on-treatment viral kinetics and approximately 2-fold increased sustained virologic response (SVR) rates in HCV genotype 1 and 4 patients. In HCV genotype 1 patients, IL28B variations were shown to be the strongest pre-treatment predictor of virologic response. In the treatment of HCV genotype 2 and 3 infected patients, IL28B variations play only a minor role. Preliminary data indicate that IL28B variations are also associated with treatment outcome of regimens, including directly acting antiviral (DAA) agents, though their impact seems to be attenuated compared to standard treatment. Here, we review these important findings and discuss possible implications for clinical decision making in the treatment of HCV infection.
Herb induced liver injury (HILI) is a particular challenge that also applies to purported cases presumably caused by black cohosh (BC), an herb commonly used to treat menopausal symptoms. We analyzed and reviewed all published case reports and spontaneous reports of initially alleged BC hepatotoxicity regarding quality of case details and causality assessments. Shortcomings of data quality were more evident in spontaneous reports of regulatory agencies compared to published case reports, but assessments with the scale of CIOMS (Council for the International Organizations of Sciences) or its updated version revealed lack of causality for BC in all cases. The applied causality methods are structured, quantitative, and liver specific with clear preference over an ad hoc causality method or the liver unspecific Naranjo scale. Reviewing the case data and the reports dealing with quality specifications of herbal BC products, there is general lack of analysis with respect to authentication of BC in the BC products used by the patients. However, in one single regulatory study, there was a problem of BC authentication in the analysed BC products, and other reports addressed the question of impurities and adulterants in a few BC products. It is concluded that the use of BC may not exert an overt hepatotoxicity risk, but quality problems in a few BC products were evident that require additional regulatory quality specifications.
Defects in apoptosis contribute to treatment resistance and poor outcome of pancreatic cancer, calling for novel therapeutic strategies. Here, we provide the first evidence that nuclear factor (NF) κB is required for Smac mimetic– mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis. The Smac mimetic BV6 cooperates with gemcitabine to reduce cell viability and to induce apoptosis. In addition, BV6 significantly enhances the cytotoxicity of several anticancer drugs against pancreatic carcinoma cells, including doxorubicin, cisplatin, and 5-fluorouracil. Molecular studies reveal that BV6 stimulates NF-κB activation, which is further increased in the presence of gemcitabine. Importantly, inhibition of NF-κB by overexpression of the dominant-negative IκBα superrepressor significantly decreases BV6- and gemcitabine-induced apoptosis, demonstrating that NF-κB exerts a proapoptotic function in this model of apoptosis. In support of this notion, inhibition of tumor necrosis factor α (TNFα) by the TNFα blocking antibody Enbrel reduces BV6- and gemcitabine-induced activation of caspase 8 and 3, loss of mitochondrial membrane potential, and apoptosis. By demonstrating that BV6 and gemcitabine trigger a NF-κB–dependent, TNFα-mediated loop to activate apoptosis signaling pathways and caspase-dependent apoptotic cell death, our findings have important implications for the development of Smac mimetic–based combination protocols in the treatment of pancreatic cancer.
Searching for new strategies to bypass apoptosis resistance, we investigated the potential of the Smac mimetic BV6 in Jurkat leukemia cells deficient in key molecules of the death receptor pathway. Here, we demonstrate for the first time that Smac mimetic primes apoptosis-resistant, FADD- or caspase-8-deficient leukemia cells for TNFα-induced necroptosis in a synergistic manner. In contrast to TNFα, Smac mimetic significantly enhances CD95-induced apoptosis in wild-type but not in FADD-deficient cells. Interestingly, Smac mimetic- and TNFα-mediated cell death occurs without characteristic features of apoptosis (i.e., caspase activation, DNA fragmentation) in FADD-deficient cells. By comparison, Smac mimetic and TNFα trigger activation of caspase-8, -9, and -3 and DNA fragmentation in wild-type cells. Consistently, the caspase inhibitor zVAD.fmk fails to block Smac mimetic- and TNFα-triggered cell death in FADD- or caspase-8-deficient cells, while it confers protection in wild-type cells. By comparison, necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic- and TNFα-induced cell death in FADD- or caspase-8-deficient. Thus, Smac mimetic enhances TNFα-induced cell death in leukemia cells via two distinct pathways in a context-dependent manner: it primes apoptosis-resistant cells lacking FADD or caspase-8 to TNFα-induced, RIP1-dependent and caspase-independent necroptosis, whereas it sensitizes apoptosis-proficient cells to TNFα-mediated, caspase-dependent apoptosis. These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance.
Background & Aims: Thrombopoietin receptor agonists are a new class of compounds licenced for the treatment of immune thrombocytopenic purpura. They are currently being studied for patients with thrombopenia in advanced liver disease or under therapy for hepatitis C. There are indications that the risk for development of portal vein thrombosis in patients with advanced liver cirrhosis might be increased under therapy with thrombopoietin receptor agonists. We report a case of a patient with Child class B liver cirrhosis with concurrent immune thrombocytopenic purpura that developed portal vein thrombosis under therapy with the thrombopoietin receptor agonist romiplostim.
Methods: A 50-year-old woman with hepatitis C virus associated immune thrombocytopenic purpura and Child class B liver cirrhosis presented in our emergency with rapidly evolving hydropic decompensation and general malaise. For immune thrombocytopenic purpura, the patient was started on the thrombopoietin receptor agonist romiplostim nine months ago.
Results: During hospitalization, the platelet count was measured above 330,000/μl and partial portal vein thrombosis was diagnosed by imaging studies. The thrombotic event was assumed to be associated with the romiplostim treatment for immune thrombocytopenic purpura via excessive elevation of platelet count. After anticoagulation with heparin and cessation of romiplostim treatment, complete recanalisation of the portal vein was achieved.
Conclusions: We conclude that romiplostim should be used with precaution in patients with hepatitis C-associated immune thrombocytopenic purpura and advanced liver cirrhosis as the risk for thrombotic complications may increase significantly.