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| 2. |
- Lindholm, L, et al.
(författare)
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Genetic re-targeting of adenovirus using a hyperstable scFv domain and an affibody (R) molecule against Her2/neu
- 2004
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 9, s. S250-S250
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Tidskriftsartikel (refereegranskat)abstract
- One important goal in gene therapy is to develop adenovirus (Ad) vectors that are genetically de-targeted as well as re-targeted. Genetic re-targeting of Ad using complex cell-binding ligands has previously not been possible. We have previously demonstrated that ligands for genetic re-targeting of adenoviruses must be able to fold correctly in the cytoplasm of virus producing cells, a milieu that is not conducive to the formation of disulphide bonds. Here, we describe functional Ad5 viruses with fibers and pIX capsid proteins genetically modified to contain two types of complex ligands. One is affibody® molecules, corresponding to small (6 kDa) binding proteins developed by combinatorial protein engineering using a single three-helix bundle staphylococcal protein A domain. The other type is hyperstable antibody scFv domains. The affibody molecule used here (ZH2N) is directed against Her2/neu. Recombinant viruses were constructed with ZH2N in three different positions: (i) at the C-terminus of shaft repeat 7 of de-knobbed fibers; (ii) at the C-terminus of pIX; and (iii) in the HI-loop of the fiber knob. Each of the viruses exhibited a characteristic phenotype regarding fiber content, growth and ability to infect Her2/neu expressing cells. In order to test the potentials of scFv liganded Ad vectors, a hyperstable antibody scFv against b-galactosidase was genetically incorporated into knobless fibers, in tandem with a mutated protein A domain reactive with IgG1 Fc that targeted the virus to Fc-expressing 293 cells. These fibers could be rescued into viable virions that retained the original antigen binding specificity of the scFv, demonstrating the basic potential of hyperstable scFvs for genetic re-targeting of Ad. Quite unexpectedly, the fiber content of Ad with knobless, scFv containing fibers was close to normal in contrast to other Ad with knobless fibers that generally has a much reduced fiber content. The hyperstable scFv was further fused to the C-terminus of the capsid protein pIX. The recombinant molecules could be rescued into viable viruses with wt fibers. The scFv retained its binding-specificity on the recombinant virions. The results demonstrate that, contrary to current beliefs, it is possible to construct Ad that genetically incorporates functional scFvs and other complex ligands into the virus fiber and pIX. The feasibility is demonstrated by the creation of different viruses that are re-targeted to Her2/neu. These viruses are currently in pre-clinical development.
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| 3. |
- Suempelmann, R., et al.
(författare)
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Perioperative fasting times in children and adolescents
- 2022
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Ingår i: Anasthesiologie und Intensivmedizin. - : AKTIV DRUCK & VERLAG GMBH. - 0170-5334 .- 1439-0256. ; 63, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- The German Scientific Working Group for Paediatric Anaesthesia (Wissenschaftlicher Arbeitskreis Kinderansthesie, WAKKA) of the German Society for Anaesthesia and Intensive Care Medicine (DGAI) has updated their current recommendations on preoperative fasting in children from 2007, along with the preoperative fasting statement of the German Association of Anaesthesiologists (Berufsverband Deutscher Anasthesisten, BDA) and DGAI from 2016 in agreement with the new evidence-based European Guideline of the European Society of Anaesthesiology and Intensive Care (ESAIC) of 2022 - and transferred it into the S1 Guideline format of the Association of the Scientific. Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgeselischaften e. V., AWMF). This revision became necessary because recent studies had shown that optimized fasting times improved hornoeostasis and well-being of the children, while the risk of regurgitation and aspiration had not increased. On the other hand, long periods of fasting might be the cause of misbehaviour, stress, iatrogenic dehydration and catabolism. The updated S1 Guideline therefore recommends shorter fasting times of 4 hours for small, light meals and/or formula or cow's milk (still 6 hours for a full meal), 3 hours for breast milk, and 1 hour for clear fluids (6-4-3-1 Rule). In addition, the new S1 Guideline contains further recommendations for children with concomitant diseases that are of relevance to anaesthesia, for the application of ultrasound to examine the stomach content prior to the induction of anaesthesia, for postoperative fasting and the implementation of the new rules in clinical practice.
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| 7. |
- Enblad P., Frykholm P., Valtysson J., Silander H C., Andersson J., Fasth K J., Watanabe Y., Långström B., Hillered L., Persson L.
(författare)
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Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography
- 2001
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Ingår i: Stroke. ; :32 (7), s. 1574-80
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Ferreira, Catarina, et al.
(författare)
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Genetic variation in the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain
- 2019
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 220, s. 748-759
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria harboring conjugative plasmids have the potential for spreading antibiotic resistance through horizontal gene transfer. It is described that the selection and dissemination of antibiotic resistance is enhanced by stressors, like metals or antibiotics, which can occur as environmental contaminants. This study aimed at unveiling the composition of the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain (H1FC54) under different mating conditions. To meet this objective, plasmid pulsed field gel electrophoresis, optical mapping analyses and DNA sequencing were used in combination with phenotype analysis. Strain H1FC54 was observed to harbor five plasmids, three of which were conjugative and two of these, pH1FC54_330 and pH1FC54_140, contained metal and antibiotic resistance genes. Transconjugants obtained in the absence or presence of tellurite (0.5 μM or 5 μM), arsenite (0.5 μM, 5 μM or 15 μM) or ceftazidime (10 mg/L) and selected in the presence of sodium azide (100 mg/L) and tetracycline (16 mg/L) presented distinct phenotypes, associated with the acquisition of different plasmid combinations, including two co-integrate plasmids, of 310 kbp and 517 kbp. The variable composition of the conjugative plasmidome, the formation of co-integrates during conjugation, as well as the transfer of non-transferable plasmids via co-integration, and the possible association between antibiotic, arsenite and tellurite tolerance was demonstrated. These evidences bring interesting insights into the comprehension of the molecular and physiological mechanisms that underlie antibiotic resistance propagation in the environment.
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