Development of the body mass index in an orthopedic patient group before and after implantation of a total hip or knee arthroplasty

Einleitung: Aktuell ist eine Zunahme des Body Mass Indexes in der Weltbevölkerung zu verzeichnen, welcher neben einer erhöhten Kalorienzufuhr auch durch einen Bewegungsmangel hervorgerufen wird. Vor diesem Hintergrund erwarten Patienten mit Kox- und Gonarthrose neben der Schmerzreduktion und verbesserten Gelenkbeweglichkeit auch eine Gewichtsabnahme nach endoprothetischer Versorgung. Wir postulierten, dass Patienten, die an einer Kox- oder Gonarthrose leiden, einen erhöhten BMI gegenüber der Allgemeinbevölkerung aufweisen und analog zur Weltbevölkerung ein stetiger BMI-Anstieg seit 2010 zu verzeichnen ist. Des Weiteren postulierten wir, dass Patienten mit einer Kox- und Gonarthrose, die sich eines totalen Gelenkersatzes unterziehen, im postoperativen Verlauf einen niedrigeren BMI aufweisen als präoperativ. Zudem untersuchten wir im Follow-Up die Inzidenz von Komplikationen nach Implantation einer Totalendoprothese. Material/ Methoden: In diese retrospektive Datenanalyse mit einem Follow-Up von drei Jahren wurden 812 Patienten einbezogen, die eine Hüft- oder Knie-Totalendoprothese am Centrum für Muskuloskeletale Chirurgie der Charité-Universitätsmedizin Berlin erhalten haben. Eingeschlossen wurden zudem alle Patienten mit primärer und sekundärer Kox- und Gonarthrose (ICD M16.0 - M16.9 und M17.0 - M17.9). Als Kontrollkohorte wurden Daten des Mikrozensus des statistischen Bundesamtes ausgewertet. Für das Follow-Up wurden die Patienten telefonisch und postalisch kontaktiert, um ihr Gewicht und aktuelle Symptome in Bezug auf ihre Totalendoprothese zu erfragen. Ergebnisse: Es zeigte sich ein Anstieg des Gewichts sowohl der Allgemeinbevölkerung (2,75 ±0,75 vs. 2,76 ±0,76 nach WHO-Klassifikation) als auch der orthopädischen Patienten (3,04 ±0,87 vs. 3,20 ±0,82 nach WHO-Klassifikation) von 2009/10 zu 2013. Außerdem zeigte sich ein deutlich größerer Anteil an adipösen Patienten in der orthopädischen Patientengruppe (37,55%) als in der Allgemeinbevölkerung (18,02%). Im drei Jahres Follow-Up zeigte sich ein signifikanter Gewichtsanstieg der orthopädischen Patienten (p < 0,001). Zwischen einem präoperativ erhöhten BMI und postoperativen Komplikationen konnte kein signifikanter Zusammenhang festgestellt werden (p = 0,690). Schlussfolgerung: Es konnte nachgewiesen werden, dass orthopädische Patienten mit einer Kox- oder Gonarthrose einen höheren BMI aufweisen als die deutsche Allgemeinbevölkerung und, dass der BMI unserer orthopädischen Patientengruppe, im untersuchten Zeitraum ansteigt. Außerdem konnten wir zeigen, dass Kox- und Gonarthrose Patienten drei Jahre nach Implantation einer Totalendoprothese signifikant an Gewicht zunehmen. Die Erwartung vieler Patienten durch die Implantation einer Gelenkendoprothese eine Gewichtsabnahme zu erwirken kann also in unserer Studie nicht bestätigt werden.Introduction: There is currently an increase of the Body Mass Index in the world population, which, in addition to an increased calorie intake, is also caused by a lack of exercise. Against this background, patients with osteoarthrosis of the hip or knee expect not only pain reduction and improved joint mobility, but also weight loss after endoprosthetic treatment. We postulated that patients suffering from osteoarthrosis of the hip or knee have an increased BMI compared to the general population and, analogous to the global population, have shown a steady increase in BMI since 2010. Furthermore, we postulated that patients with osteoarthrosis of the hip or knee who undergo total joint replacement have a lower BMI in the postoperative course than preoperatively. In addition, in a follow-up we investigated the incidence of complications after total joint arthroplasty. Material and Methods: In this retrospective data analysis with a follow-up of 3 years, 812 patients were included who had received a total hip or knee endoprosthesis at the Center for Musculoskeletal Surgery at the Charité-Universitätsmedizin Berlin. All patients with primary and secondary osteoarthrosis of the hip and knee (ICD M16.0 - M16.9 and M17.0 - M17.9) were included. Data from the microcensus of the Federal Statistical Office were evaluated as a control cohort. For the follow-up, the patients were contacted by phone and mail to inquire about their weight and current symptoms in relation to their total endoprosthesis. Results: There was an increase in the weight of both the general population (2.75 ± 0.75 vs. 2.76 ± 0.76 according to WHO classification) and of the orthopedic patients (3.04 ± 0.87 vs. 3.20 ± 0, 82 according to WHO classification) from 2009/10 to 2013. In addition, there was a significantly higher proportion of obese patients in the orthopedic patient collective (37.55%) than in the general population (18.02%). The three-year follow-up showed a significant increase in the weight of the orthopedic patients (p <0.001). No significant difference could be shown between a preoperatively increased BMI and complications postoperatively (p = 0.690). Conclusion: We were able to prove that orthopedic patients with osteoarthrosis of the hip or knee have a higher BMI than the general German population and that the BMI of our orthopedic patients increased in the period examined. We were also able to show that patients with osteoarthrosis of the hip or knee gain significant weight 3 years after total In our study, the desire of many patients to achieve weight loss through a total joint arthroplasty can therefore not be confirmed

N-Terminal His-Tagged AtTPR7 Interactions with Hsp70 and Hsp90 Proteins

Post-translational protein import into organelles is an important process to maintain cellular functions. During preprotein transport in the cytosol, chaperones, such as heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90), are functioning to prevent aggregation and to maintain the correct protein folding of preproteins. This research was conducted in order to understand the chaperone-mediated, post-translational import of preproteins into the endoplasmic reticulum of Arabidopsis thaliana. AtTPR7 (Arabidopsis thaliana Tetratrico Peptide Repeat 7) is found in the endoplasmic reticulum and contains TPR domain, which mediates protein interaction with cytosolic Hsp70 and Hsp90. In this study, recombinant AtTPR7 was expressed in E. coli BL21 (DE3)-RIPL cells and purified using an N-terminal His-tag. In order to study the interactions of the protein with the chaperones, we used pulldown and Western blot assays. We could thereby show that the N-terminally His-tagged AtTPR7 protein interacted with Hsp70 and Hsp90

The ER luminal C‐terminus of AtSec62 is critical for male fertility and plant growth in Arabidopsis thaliana

Protein translocation into the endoplasmic reticulum (ER) occurs either co‐ or post‐translationally through the Sec translocation system. The Arabidopsis Sec post‐translocon is composed of the protein‐conducting Sec61 complex, the chaperone‐docking protein AtTPR7, the J‐domain‐containing proteins AtERdj2A/B and the yet uncharacterized AtSec62. Yeast Sec62p is suggested to mainly function in post‐translational translocation, whereas mammalian Sec62 also interacts with ribosomes. In Arabidopsis, loss of AtSec62 leads to impaired growth and drastically reduced male fertility indicating the importance of AtSec62 in protein translocation and subsequent secretion in male gametophyte development. Moreover, AtSec62 seems to be divergent in function as compared with yeast Sec62p, since we were not able to complement the thermosensitive yeast mutant sec62‐ts. Interestingly, AtSec62 has an additional third transmembrane domain in contrast to its yeast and mammalian counterparts resulting in an altered topology with the C‐terminus facing the ER lumen instead of the cytosol. In addition, the AtSec62 C‐terminus has proven to be indispensable for AtSec62 function, since a construct lacking the C‐terminal region was not able to rescue the mutant phenotype in Arabidopsis. We thus propose that Sec62 acquired a unique topology and function in protein translocation into the ER in plants

The ABC transporter family efflux pump PvdRT‐OpmQ of Pseudomonas putida KT2440: purification and initial characterization

Tripartite efflux systems of the ABC-type family transport a variety of substrates and contribute to the antimicrobial resistance of Gram-negative bacteria. PvdRT-OpmQ, a member of this family, is thought to be involved in the secretion of the newly synthesized and recycled siderophore pyoverdine in Pseudomonas species. Here, we purified and characterized the inner membrane component PvdT and the periplasmic adapter protein PvdR of the plant growth-promoting soil bacterium Pseudomonas putida KT2440. We show that PvdT possesses an ATPase activity that is stimulated by the addition of PvdR. In addition, we provide the first biochemical evidence for direct interactions between pyoverdine and PvdRT

Stabilization and humanization of a single-chain Fv antibody fragment specific for human lymphocyte antigen CD19 by designed point mutations and CDR-grafting onto a human framework

A single-chain Fv (scFv) fragment derived from the murine antibody 4G7, specific for human lymphocyte CD19, was engineered for stability and expression in Escherichia coli in view of future use as a therapeutic protein. We compared two orthogonal knowledge-based procedures. In one approach, we designed a mutant with 14 single amino-acid substitutions predicted to correct destabilizing residues in the 4G7-wt sequence to create 4G7-mut. In the second variant, the murine CDRs were grafted to the human acceptor framework huVκ3-huVH3, with 11 additional point mutations introduced to obtain a better match between CDR graft and acceptor framework, to arrive at 4G7-graft. Compared to 4G7-wt, 4G7-mut showed greater thermodynamic stability in guanidinium chloride-induced equilibrium denaturation experiments and somewhat greater stability in human serum. The loop graft maintained the comparatively high stability of the murine loop donor, but did not improve it further. Our analysis indicates that this is due to subtle strain introduced between CDRs and framework, mitigating the otherwise highly favorable properties of the human acceptor framework. This slight strain in the loop graft is also reflected in the binding affinities for CD19 on leukemic cells of 8.4 nM for 4G7-wt, 16.4 nM for 4G7-mut and 30.0 nM for 4G7-graft. This comparison of knowledge-based mutation and loop-grafting-based approaches will be important, when moving molecules forward to therapeutic application

Удаление сернистых соединений из дизельных топлив с использованием металлосодержащих ионных жидкостей

Данная статья посвящена проблеме удаления сернистых соединений из дизельных топлив. Представлены характеристики полученных экстракционных систем на основе ионных жидкостей и солей металлов (СuBr[2], CoBr[2], NiBr[2]). Показана возможность использования комплексов ионных жидкостей с солями металлов в качестве экстрагентов для удаления серы из дизельного топлива

Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP)-targeted delivery of soluble TRAIL potently inhibits melanoma outgrowth in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Advanced melanoma is characterized by a pronounced resistance to therapy leading to a limited patient survival of ~6 - 9 months. Here, we report on a novel bifunctional therapeutic fusion protein, designated anti-MCSP:TRAIL, that is comprised of a melanoma-associated chondroitin sulfate proteoglycan (MCSP)-specific antibody fragment (scFv) fused to soluble human TRAIL. MCSP is a well-established target for melanoma immunotherapy and has recently been shown to provide important tumorigenic signals to melanoma cells. TRAIL is a highly promising tumoricidal cytokine with no or minimal toxicity towards normal cells. Anti-MCSP:TRAIL was designed to <b>1</b>. selectively accrete at the cell surface of MCSP-positive melanoma cells and inhibit MCSP tumorigenic signaling and <b>2</b>. activate apoptotic TRAIL-signaling.</p> <p>Results</p> <p>Treatment of a panel of MCSP-positive melanoma cell lines with anti-MCSP:TRAIL induced TRAIL-mediated apoptotic cell death within 16 h. Of note, treatment with anti-MCSP:sTRAIL was also characterized by a rapid dephosphorylation of key proteins, such as FAK, implicated in MCSP-mediated malignant behavior. Importantly, anti-MCSP:TRAIL treatment already inhibited anchorage-independent growth by 50% at low picomolar concentrations, whereas > 100 fold higher concentrations of non-targeted TRAIL failed to reduce colony formation. Daily i.v. treatment with a low dose of anti-MCSP:TRAIL (0.14 mg/kg) resulted in a significant growth retardation of established A375 M xenografts. Anti-MCSP:TRAIL activity was further synergized by co-treatment with rimcazole, a σ-ligand currently in clinical trials for the treatment of various cancers.</p> <p>Conclusions</p> <p>Anti-MCSP:TRAIL has promising pre-clinical anti-melanoma activity that appears to result from combined inhibition of tumorigenic MCSP-signaling and concordant activation of TRAIL-apoptotic signaling. Anti-MCSP:TRAIL alone, or in combination with rimcazole, may be of potential value for the treatment of malignant melanoma.</p

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

Roles of PsbI and PsbM in photosystem II dimer formation and stability studied by deletion mutagenesis and X-ray crystallography

PsbM and PsbI are two low molecular weight subunits of photosystem II (PSII), with PsbM being located in the center, and PsbI in the periphery, of the PSII dimer. In order to study the functions of these two subunits from a structural point of view, we crystallized and analyzed the crystal structure of PSII dimers from two mutants lacking either PsbM or PsbI. Our results confirmed the location of these two subunits in the current crystal structure, as well as their absence in the respective mutants. The relative contents of PSII dimers were found to be decreased in both mutants, with a concomitant increase in the amount of PSII monomers, suggesting a destabilization of PSII dimers in both of the mutants. On the other hand, the accumulation level of the overall PSII complexes in the two mutants was similar to that in the wild-type strain. Treatment of purified PSII dimers with lauryldimethylamine N-oxide at an elevated temperature preferentially disintegrated the dimers from the PsbM deletion mutant into monomers and CP43-less monomers, whereas no significant degradation of the dimers was observed from the PsbI deletion mutant. These results indicate that although both PsbM and PsbI are required for the efficient formation and stability of PSII dimers in vivo, they have different roles, namely, PsbM is required directly for the formation of dimers and its absence led to the instability of the dimers accumulated. On the other hand, PsbI is required in the assembly process of PSII dimers in vivo; once the dimers are formed, PsbI was no longer required for its stability