RepoMed (Medizinische Hochschule Hannover)
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The role of innate immune response in controlling murine gammaherpesvirus 68 acute infection in vivo
Get PDFClostridium novyi’s Alpha-Toxin Changes Proteome and Phosphoproteome of HEp-2 Cells
Get PDFC. novyi type A produces the alpha-toxin (TcnA) that belongs to the large clostridial glucosylating toxins (LCGTs) and is able to modify small GTPases by N-acetylglucosamination on conserved threonine residues. In contrast, other LCGTs including Clostridioides difficile toxin A and toxin B (TcdA; TcdB) modify small GTPases by mono-o-glucosylation. Both modifications inactivate the GTPases and cause strong effects on GTPase-dependent signal transduction pathways and the consequent reorganization of the actin cytoskeleton leading to cell rounding and finally cell death. However, the effect of TcnA on target cells is largely unexplored. Therefore, we performed a comprehensive screening approach of TcnA treated HEp-2 cells and analyzed their proteome and their phosphoproteome using LC-MS-based methods. With this data-dependent acquisition (DDA) approach, 5086 proteins and 9427 phosphosites could be identified and quantified. Of these, 35 proteins were found to be significantly altered after toxin treatment, and 1832 phosphosites were responsive to TcnA treatment. By analyzing the TcnA-induced proteomic effects of HEp-2 cells, 23 common signaling pathways were identified to be altered, including Actin Cytoskeleton Signaling, Epithelial Adherens Junction Signaling, and Signaling by Rho Family GTPases. All these pathways are also regulated after application of TcdA or TcdB of C. difficile. After TcnA treatment the regulation on phosphorylation level was much stronger compared to the proteome level, in terms of both strength of regulation and the number of regulated phosphosites. Interestingly, various signaling pathways such as Signaling by Rho Family GTPases or Integrin Signaling were activated on proteome level while being inhibited on phosphorylation level or vice versa as observed for the Role of BRCA1 in DNA Damage Response. ZIP kinase, as well as Calmodulin-dependent protein kinases IV & II, were observed as activated while Aurora-A kinase and CDK kinases tended to be inhibited in cells treated with TcnA based on their substrate regulation pattern
Lokalinfiltrationsanalgesie (LIA) versus Nervus Femoralis Katheter (NFK) bei Kniegelenk-Ersatz Operationen
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Higher revision rate for posterior cruciate-retaining than posterior-stabilized total knee arthroplasty for the treatment of valgus osteoarthritis
Get PDFPurpose Determining the point at which a valgus deformity requires a more invasive therapy --- in this case PS TKA --- is surgically challenging. Retaining the posterior cruciate ligament has both advantages and disadvantages. The aim was to evaluate the failure rate and clinical outcomes. Methods 248 patients with valgus gonarthrosis underwent surgical treatment: 167 CR TKA cases and 81 PS TKA cases. The KOOS and the OKS were recorded, and 201 patients (133 CR, 68 PS) were recruited into the retrospective study. The influence of BMI and degree of preoperative valgus deformity on the clinical outcome was determined. The revision rate was documented and analysed. Results Of 201 patients, 10 required revision surgery owing to instability (10/133 CR, 0/68 PS). Based on the KOOS and the OKS, no significant difference between CR TKA and PS TKA was found. BMI and degree of valgus deformity had no effect on the clinical outcome. Conclusions No difference in the clinical outcome between the CR and PS TKA patients was found. In the CR group, significantly more patients showed ‘excellent’ OKS than in the PS group. However, 8.0% of the patients in the CR group and none in the PS group underwent surgery due to instability. A higher rate of dissatisfied patients in the CR group is likely. In our clinic, we no longer perform CR TKA for valgus cases
