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21.
M L Weil W A Leiva D C Heiner W W Tourtellotte 《Journal of immunology (Baltimore, Md. : 1950)》1975,115(6):1603-1606
SSPE brain homogenate extracted at pH 7.4 yields immunoglobulin with a 4- to 5-fold greater hemagglutination inhibition activity per microgram of IgG than serum from the same patient. Serial washing of the homogenate results in a low level steady-state release of IgG. Elution of the washed sediment with pH 2.5, 0.1 M glycine buffer results in a 2- to 3-fold increase in recovery of hemagglutination inhibition activity with a greater hemagglutination inhibition activity per milligram of IgG than the IgG recovered by phosphate-saline extraction at pH 7.4. 相似文献
22.
Oscar Lamas Longarela Tobias T. Schmidt Katrin Sch?neweis Raffaella Romeo Heiner Wedemeyer Stephan Urban Andreas Schulze 《PloS one》2013,8(3)
The hepatitis delta virus (HDV) is a small, defective RNA virus that requires the presence of the hepatitis B virus (HBV) for its life cycle. Worldwide more than 15 million people are co-infected with HBV and HDV. Although much effort has been made, the early steps of the HBV/HDV entry process, including hepatocyte attachment and receptor interaction are still not fully understood. Numerous possible cellular HBV/HDV binding partners have been described over the last years; however, so far only heparan sulfate proteoglycans have been functionally confirmed as cell-associated HBV attachment factors. Recently, it has been suggested that ionotrophic purinergic receptors (P2XR) participate as receptors in HBV/HDV entry. Using the HBV/HDV susceptible HepaRG cell line and primary human hepatocytes (PHH), we here demonstrate that HDV entry into hepatocytes depends on the interaction with the glycosaminoglycan (GAG) side chains of cellular heparan sulfate proteoglycans. We furthermore provide evidence that P2XR are not involved in HBV/HDV entry and that effects observed with inhibitors for these receptors are a consequence of their negative charge. HDV infection was abrogated by soluble GAGs and other highly sulfated compounds. Enzymatic removal of defined carbohydrate structures from the cell surface using heparinase III or the obstruction of GAG synthesis by sodium chlorate inhibited HDV infection of HepaRG cells. Highly sulfated P2XR antagonists blocked HBV/HDV infection of HepaRG cells and PHH. In contrast, no effect on HBV/HDV infection was found when uncharged P2XR antagonists or agonists were applied. In summary, HDV infection, comparable to HBV infection, requires binding to the carbohydrate side chains of hepatocyte-associated heparan sulfate proteoglycans as attachment receptors, while P2XR are not actively involved. 相似文献
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24.
Peter Dollinger Theo Pagel Katrin Baumgartner Dag Encke Heiner Engel Andreas Filz 《Der Zoologische Garten (in deutscher Sprache / in German)》2013,82(5-6):293-339
The techniques and biological functions of avian flight are briefly presented. The reasons for rendering zoo birds flightless are explained taking into account the tasks and obligations of modern zoos, and the various deflighting procedures are described. The legal situation regarding deflighting as it currently exists in Germany and other countries is clarified. It is discussed in detail under which circumstances it would be justifiable to render a bird flightless, to what extent keeping the birds in aviaries would be an alternative and whether reversible or irreversible methods should be preferred. A legal opinion has been sought which came to the conclusion that even under the restrictive Animal Welfare Law of Germany interventions to render a bird flightless were admissible if based on veterinary indication on a case-by-case basis. Such indication may be justified by the anticipation that a bird may be injured or die from an accident in future if not deflighted. Contrary to the views of some legal experts commenting on the German Animal Welfare Law the authors consider feather clipping not to be an intervention prohibited under the law. In the interest of the good functioning of european and international breeding programmes the authors suggest that the German legislation should be modified with a view of containing a general derogation for rendering flightless at least certain species of zoo birds. 相似文献
25.
Benjamin Maasoumy Kerstin Port Antoaneta Angelova Markova Beatriz Calle Serrano Magdalena Rogalska-Taranta Lisa Sollik Carola Mix Janina Kirschner Michael P. Manns Heiner Wedemeyer Markus Cornberg 《PloS one》2013,8(2)
Background
HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.Methods
All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.Results
208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.Conclusions
P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options. 相似文献26.
Karen?van Eunen Catharina?M.?L.?Volker-Touw Albert?Gerding Aycha?Bleeker Justina?C.?Wolters Willemijn?J.?van Rijt Anne-Claire?M.?F.?Martines Klary?E.?Niezen-Koning Rebecca?M.?Heiner Hjalmar?Permentier Albert?K.?Groen Terry?G.?J.?Derks Barbara?M.?BakkerEmail author 《BMC biology》2016,14(1):107
Background
Defects in genes involved in mitochondrial fatty-acid oxidation (mFAO) reduce the ability of patients to cope with metabolic challenges. mFAO enzymes accept multiple substrates of different chain length, leading to molecular competition among the substrates. Here, we combined computational modeling with quantitative mouse and patient data to investigate whether substrate competition affects pathway robustness in mFAO disorders.Results
First, we used comprehensive biochemical analyses of wild-type mice and mice deficient for medium-chain acyl-CoA dehydrogenase (MCAD) to parameterize a detailed computational model of mFAO. Model simulations predicted that MCAD deficiency would have no effect on the pathway flux at low concentrations of the mFAO substrate palmitoyl-CoA. However, high concentrations of palmitoyl-CoA would induce a decline in flux and an accumulation of intermediate metabolites. We proved computationally that the predicted overload behavior was due to substrate competition in the pathway. Second, to study the clinical relevance of this mechanism, we used patients’ metabolite profiles and generated a humanized version of the computational model. While molecular competition did not affect the plasma metabolite profiles during MCAD deficiency, it was a key factor in explaining the characteristic acylcarnitine profiles of multiple acyl-CoA dehydrogenase deficient patients. The patient-specific computational models allowed us to predict the severity of the disease phenotype, providing a proof of principle for the systems medicine approach.Conclusion
We conclude that substrate competition is at the basis of the physiology seen in patients with mFAO disorders, a finding that may explain why these patients run a risk of a life-threatening metabolic catastrophe.27.
Socioeconomic status and anthropometric changes—A meta‐analytic approach from seven German cohorts
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Johannes Haerting Saskia Hartwig Daniel Tiller Daniel Medenwald Susanne Vogt Barbara Thorand Rolf Holle Ursula Bachlechner Heiner Boeing Benedikt Merz Ute Nöthlings Sabrina Schlesinger Sabine Schipf Till Ittermann Nicole Aumann Anja Schienkiewitz Marjolein Haftenberger Karin H. Greiser Jasmine Neamat‐Allah Verena Katzke Alexander Kluttig 《Obesity (Silver Spring, Md.)》2016,24(3):710-718
28.
Patrick Stelmach Christian Wedemeyer Lena Fuest Gina Kurscheid Thorsten Gehrke Stefanie Klenke Marcus J?ger Max D. Kauther Hagen S. Bachmann 《PloS one》2016,11(2)
Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15–3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers. 相似文献
29.
Coupling of conformational folding and disulfide-bond reactions in oxidative folding of proteins 总被引:6,自引:0,他引:6
The oxidative folding of proteins consists of conformational folding and disulfide-bond reactions. These two processes are coupled significantly in folding-coupled regeneration steps, in which a single chemical reaction (the "forward" reaction) converts a conformationally unstable precursor species into a conformationally stable, disulfide-protected successor species. Two limiting-case mechanisms for folding-coupled regeneration steps are described. In the folded-precursor mechanism, the precursor species is preferentially folded at the moment of the forward reaction. The (transient) native structure increases the effective concentrations of the reactive thiol and disulfide groups, thus favoring the forward reaction. By contrast, in the quasi-stochastic mechanism, the forward reaction occurs quasi-stochastically in an unfolded precursor; i.e., reactive groups encounter each other with a probability determined primarily by loop entropy, albeit modified by conformational biases in the unfolded state. The resulting successor species is initially unfolded, and its folding competes with backward chemical reactions to the unfolded precursors. The folded-precursor and quasi-stochastic mechanisms may be distinguished experimentally by the dependence of their kinetics on factors affecting the rates of thiol--disulfide exchange and conformational (un)folding. Experimental data and structural and biochemical arguments suggest that the quasi-stochastic mechanism is more plausible than the folded-precursor mechanism for most proteins. 相似文献
30.
Wedemeyer N Greve B Uthe D Pötter T Denklau D Severin E Hacker-Klom U Köhnlein W Göhde W 《Mutation research》2001,473(1):73-84
Determination of the genotoxic effects of ionizing radiation, especially at low-doses, is of great importance for risk assessment, e.g. in radiological diagnostics. The human-hamster hybrid A(L) cell line has been shown previously to be a well-suited in vitro model for the study of mutations induced by various mutagens. The A(L) cells contain a standard set of hamster chromosomes and a single human chromosome 11, which confers the expression of the human cell surface protein CD59. Using CD59 specific antibodies, cells mutated in the CD59 gene can be detected and quantified by the loss of the cell surface marker. In contrast to previous studies, prior to irradiation we removed spontaneous mutants by magnetic cell separation (MACS) which allows analysis of radiation-induced mutation events only. We exposed A(L) cells to 100kV X-rays at 0.1 to 5Gy. The proportions of X-irradiation-induced CD59(-) mutants were quantified by flow cytometry after immunofluorescence labeling. Between 0.2 and 5Gy the yield of CD59 mutants was a linear function of dose. The molecular analysis of individual CD59-negative clones induced after exposure of 1, 3 and 5Gy of X-ray revealed a dose-dependent linear increase of large deletions (>6Mbp), whereas, point mutations could be seen only in spontaneous CD59 mutants or after low-dose exposure (< or =1Gy). We conclude that the modified A(L) assay presented here is appropriate for detection and quantification of non-lethal DNA lesions induced by low-dose ionizing radiation. 相似文献