RepoMed (Medizinische Hochschule Hannover)
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Tim-3 is dispensable for allergic inflammation and respiratory tolerance in experimental asthma
No full textT cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been described as a transmembrane protein, expressed on the surface of various T cells as well as different cells of innate immunity. It has since been associated with Th1 mediated autoimmune diseases and transplantation tolerance studies, thereby indicating a possible role of this receptor in counter-regulation of Th2 immune responses. In the present study we therefore directly examined the role of Tim-3 in allergic inflammation and respiratory tolerance. First, Tim-3-/- mice and wild type controls were immunized and challenged with the model allergen ovalbumin (OVA) to induce an asthma-like phenotype. Analysis of cell numbers and distribution in the bronchoalveolar lavage (BAL) fluid as well as lung histology in H&E stained lung sections demonstrated a comparable degree of eosinophilic inflammation in both mouse strains. Th2 cytokine production in restimulated cell culture supernatants and serum IgE and IgG levels were equally increased in both genotypes. In addition, cell proliferation and the distribution of different T cell subsets were comparable. Moreover, analysis of both mouse strains in our respiratory tolerance model, where mucosal application of the model allergen before immunization, prevents the development of an asthma-like phenotype, revealed no differences in any of the parameters mentioned above. The current study demonstrates that Tim-3 is dispensable not only for the development of allergic inflammation but also for induction of respiratory tolerance in mice in an OVA-based model
Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs-Influence of Smoking Behavior and Inflammation on Pharmacokinetics
No full textBoth inflammation and smoking can influence a drug's pharmacokinetic properties, i.e., its liberation, absorption, distribution, metabolism, and elimination. Depending on, e.g., pharmacogenetics, these changes may alter treatment response or cause serious adverse drug reactions and are thus of clinical relevance. Antipsychotic drugs, used in the treatment of psychosis and schizophrenia, should be closely monitored due to multiple factors (e.g., the narrow therapeutic window of certain psychotropic drugs, the chronicity of most mental illnesses, and the common occurrence of polypharmacotherapy in psychiatry). Therapeutic drug monitoring (TDM) aids with drug titration by enabling the quantification of patients' drug levels. Recommendations on the use of TDM during treatment with psychotropic drugs are presented in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; however, data on antipsychotic drug levels during inflammation or after changes in smoking behavior-both clinically relevant in psychiatry-that can aid clinical decision making are sparse. The following narrative review provides an overview of relevant literature regarding TDM in psychiatry, particularly in the context of second- and third-generation antipsychotic drugs, inflammation, and smoking behavior. It aims to spread awareness regarding TDM (most pronouncedly of clozapine and olanzapine) as a tool to optimize drug safety and provide patient-tailored treatment
Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy
No full textDirect cellular interactions of MDA-MB-231cherry breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSCGFP) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5cherry GFP breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231cherry breast cancer cells. In contrast to a spontaneous MDA-MB-231cherry induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity
Langzeitergebnisse nach chirurgischer total arterieller Koronarrevaskularisation mittels Arteria radialis als T-Graft
No full textMidterm results after tantalum cones in 1-stage knee exchange for periprosthetic joint infection: a single-center study
No full textThe Wisconsin Card Sorting Test: Split-Half Reliability Estimates for a Self-Administered Computerized Variant.
No full textSelf-administered computerized assessment has the potential to increase the reach of neuropsychological assessment. The present study reports the first split-half reliability estimates for a self-administered computerized variant of the Wisconsin Card Sorting Test (WCST), which is considered as a gold standard for the neuropsychological assessment of executive functions. We analyzed data from a large sample of young volunteers (N = 375). Split-half reliability estimates for perseveration errors, set-loss errors, and inference errors were all above 0.90. Split-half reliability estimates for response time measures on switch and repeat trials exceeded 0.95. Our results indicated sufficient split-half reliability for a self-administered computerized WCST, paving the way for an advanced digital assessment of executive functions. We discuss potential effects of test formats, administration variants, and sample characteristics on split-half reliability
Der Skelettmuskelindex im Vergleich zum Body-Mass-Index als Prädiktor für Morbidität und Mortalität nach radikaler Zystektomie beim Urothelkarzinom der Harnblase
No full textGeneration of two iPSC clones (MHHi021-A and MHHi021-B) from a patient with hypertrophic cardiomyopathy with p.Arg723Gly mutation in the MYH7 gene.
Get PDFHypertrophic cardiomyopathy (HCM) is the most common form of genetic heart disease and is characterized by abnormal thickening of the left ventricular wall and interventricular septum. Here we describe the generation of two induced pluripotent stem cell (iPSC) clones from a HCM patient, heterozygous for the p.Arg723Gly (c.2169C > G) mutation in the MYH7 gene. The generated iPSC clones may provide a useful resource for disease modelling to study the mechanisms underlying HCM pathogenesis in iPSC derived progenies, in particular cardiomyocytes
