RepoMed (Medizinische Hochschule Hannover)
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Down-Regulation of MHC Class I Expression in Human Keratinocytes Using Viral Vectors Containing US11 Gene of Human Cytomegalovirus and Cultivation on Bovine Collagen-Elastin Matrix (Matriderm®): Potential Approach for an Immune-Privileged Skin Substitute
No full textSkin transplantation, especially in burn patients, is still challenging because surgeons are faced with limited disposability of autologous donor side material. The in vitro culture of keratinocytes has become an important reconstructive option. However, only non-immunogenic allogenic keratinocytes offer the opportunity to develop a skin graft that can overcome rejection. The purpose of the study was to develop targeted gene modification of keratinocytes in order to reduce immunogenicity for the use as allogenic transplantable skin graft by decreasing the expression of MHC class I. To reduce MHC class I expression, viral vectors containing the US11 gene of human cytomegalovirus were generated and tested on their functionality using Western blotting, indirect immunofluorescence staining, and flow cytometry. Transfected keratinocytes were seeded on commercially available bovine collagen-elastin matrices and further cultured for histological and cell survival assays. Results showed transient down-regulation of MHC class I after 24 h post-transfection, with recovery of MHC class I expression after 48 h. Histological assessments showed long-term cell survival as well as histological patterns comparable to epidermal layers of healthy human skin. The data postulates the potential application of US11 transfected keratinocytes as an approach towards an immune-privileged skin substitute. Nevertheless, further studies and data are needed
Decoding hepatitis C virus entry: structural and functional determinants of the HCV entry factor CD81
No full textRobust Identification of Suitable T-Cell Subsets for Personalized CMV-Specific T-Cell Immunotherapy Using CD45RA and CD62L Microbeads
Get PDFViral infections and reactivations remain a serious obstacle to successful
hematopoietic stem cell transplantation (HSCT). When antiviral drug treatment
fails, adoptive virus-specific T-cell transfer provides an effective alternative.
Assuming that naive T cells (TN) are mainly responsible for GvHD, methods were
developed to generate naive T-cell-depleted products while preserving immune
memory against viral infections. We compared two major strategies to deplete
potentially alloreactive T cells: CD45RA and CD62L depletion and analyzed
phenotype and functionality of the resulting CD45RA(-)/CD62L(-) naive
T-cell-depleted as well as CD45RA(+)/CD62L(+) naive T-cell-enriched fractions in
the CMV pp65 and IE1 antigen model. CD45RA depletion resulted in loss of
terminally differentiated effector memory T cells re-expressing CD45RA (TEMRA),
and CD62L depletion in loss of central memory T cells (TCM). Based on these
differences in target cell-dependent and target cell-independent assays,
antigen-specific T-cell responses in CD62L-depleted fraction were consistently
3(-)5 fold higher than those in CD45RA-depleted fraction. Interestingly, we also
observed high donor variability in the CD45RA-depleted fraction, resulting in a
substantial loss of immune memory. Accordingly, we identified donors with
expected response (DER) and unexpected response (DUR). Taken together, our
results showed that a naive T-cell depletion method should be chosen
individually, based on the immunophenotypic composition of the T-cell populations
present
Quality of life and functional outcome following microsurgical fasciocutaneous vs. myocutaneous tissue transfer
No full textIdentifikation von mTORC1 als neuen Wirtsfaktor für die Hepatitis C Virus RNA Replikation
No full textHSV-1 triggers paracrine fibroblast growth factor response from cortical brain cells via immediate-early protein ICP0.
No full textBACKGROUND:Herpes simplex virus-1 (HSV-1) infections of the central nervous system (CNS) can result in HSV-1 encephalitis (HSE) which is characterized by severe brain damage and long-term disabilities. Different cell types including neurons and astrocytes become infected in the course of an HSE which leads to an activation of glial cells. Activated glial cells change their neurotrophic factor profile and modulate inflammation and repair. The superfamily of fibroblast growth factors (FGFs) is one of the largest family of neurotrophic factors comprising 22 ligands. FGFs induce pro-survival signaling in neurons and an anti-inflammatory answer in glial cells thereby providing a coordinated tissue response which favors repair over inflammation. Here, we hypothesize that FGF expression is altered in HSV-1-infected CNS cells. METHOD:We employed primary murine cortical cultures comprising a mixed cell population of astrocytes, neurons, microglia, and oligodendrocytes. Astrocyte reactivity was morphometrically monitored by an automated image analysis algorithm as well as by analyses of A1/A2 marker expression. Altered FGF expression was detected by quantitative real-time PCR and its paracrine FGF activity. In addition, HSV-1 mutants were employed to characterize viral factors important for FGF responses of infected host cells. RESULTS:Astrocytes in HSV-1-infected cortical cultures were transiently activated and became hypertrophic and expressed both A1- and A2-markers. Consistently, a number of FGFs were transiently upregulated inducing paracrine neurotrophic signaling in neighboring cells. Most prominently, FGF-4, FGF-8, FGF-9, and FGF-15 became upregulated in a switch-on like mechanism. This effect was specific for CNS cells and for a fully functional HSV-1. Moreover, the viral protein ICP0 critically mediated the FGF switch-on mechanism. CONCLUSIONS:HSV-1 uses the viral protein ICP0 for the induction of FGF-expression in CNS cells. Thus, we propose that HSV-1 triggers FGF activity in the CNS for a modulation of tissue response upon infection
A Meta-Analysis of Relationships between Measures of Wisconsin Card Sorting and Intelligence.
No full textThe Wisconsin Card Sorting Test (WCST) represents a widely utilized neuropsychological assessment technique for executive function. This meta-analysis examined the discriminant validity of the WCST for the assessment of mental shifting, considered as an essential subcomponent of executive functioning, against traditional psychometric intelligence tests. A systematic search was conducted, resulting in 72 neuropsychological samples for the meta-analysis of relationships between WCST scores and a variety of intelligence quotient (IQ) domains. The study revealed low to medium-sized correlations with IQ domains across all WCST scores that could be investigated. Verbal/crystallized IQ and performance/fluid IQ were indistinguishably associated with WCST scores. To conclude, the WCST assesses cognitive functions that might be partially separable from common conceptualizations of intelligence. More vigorous initiatives to validate putative indicators of executive function against intelligence are required
Wie ernst nimmt die Politik die Psychiatriereform?: Ein fachliches Controlling zur Umsetzung des Landespsychiatieplans Niedersachsen
No full textPotential Role of MSC/Cancer Cell Fusion and EMT for Breast Cancer Stem Cell Formation.
Get PDFSolid tumors comprise of maturated cancer cells and self-renewing cancer stem-like cells (CSCs), which are associated with various other nontumorigenic cell populations in the tumor microenvironment. In addition to immune cells, endothelial cells, fibroblasts, and further cell types, mesenchymal stroma/stem-like cells (MSC) represent an important cell population recruited to tumor sites and predominantly interacting with the different cancer cells. Breast cancer models were among the first to reveal distinct properties of CSCs, however, the cellular process(es) through which these cells are generated, maintained, and expanded within neoplastic tissues remains incompletely understood. Here, we discuss several possible scenarios that are not mutually exclusive but may even act synergistically: fusion of cancer cells with MSC to yield hybrid cells and/or the induction of epithelial-mesenchymal transition (EMT) in breast cancer cells by MSC, which can relay signals for retrodifferentiation and eventually, the generation of breast CSCs (BCSCs). In either case, the consequences may be promotion of self-renewal capacity, tumor cell plasticity and heterogeneity, an increase in the cancer cells' invasive and metastatic potential, and the acquisition of resistance mechanisms towards chemo- or radiotherapy. While specific signaling mechanisms involved in each of these properties remain to be elucidated, the present review article focusses on a potential involvement of cancer cell fusion and EMT in the development of breast cancer stem cells
