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| 2. |
- Andersson, Emma K, 1978-, et al.
(författare)
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Small molecule screening using a whole cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel anti-adenoviral compound
- 2010
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American society for microbiology. - 0066-4804 .- 1098-6596. ; 54:9, s. 3871-3877
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their anti-adenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential anti-adenoviral compounds. The assay is unique in that it is based on a replication competent adenovirus type 11p GFP-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by >/= 80% but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.
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| 3. |
- Gustafsson, Dan J, et al.
(författare)
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Adenovirus 11p downregulates CD46 early in infection
- 2010
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Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 405:2, s. 474-482
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus 11 prototype (Ad11p), belonging to species B, uses CD46 as an attachment receptor. CD46, a complement regulatory molecule, is expressed on all human nucleated cells. We show here that Ad11p virions downregulate CD46 on the surface of K562 cells as early as 5min p.i. Specific binding to CD46 by the Ad11p fiber knob was required to mediate downregulation. The complement regulatory factors CD55 and CD59 were also reduced to a significant extent as a consequence of Ad11p binding to K562 cells. In contrast, binding of Ad7p did not result in downregulation of CD46 early in infection. Thus, the presumed interaction between Ad7p and CD46 did not have the same consequences as the Ad11p-CD46 interaction, the latter virus (Ad11p) being a promising gene therapy vector candidate. These findings may lead to a better understanding of the pathogenesis of species B adenovirus infections.
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| 4. |
- Hansson, Emma K., et al.
(författare)
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Limited inter-occasion variability in relation to inter-individual variability in chemotherapy-induced myelosuppression
- 2010
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 65:5, s. 839-848
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A previously developed semi-physiological model of chemotherapy-induced myelosuppression has shown consistent system-related parameter and inter-individual variability (IIV) estimates across drugs. A requirement for dose individualization to be useful is relatively low variability between treatment courses (IOV) in relation to IIV. The objective of this study was to evaluate and compare magnitudes of IOV and IIV in myelosuppression model parameters across six different anti-cancer drug treatments.Methods: Neutrophil counts from several treatment courses following therapy with docetaxel, paclitaxel, epirubicin-docetaxel, 5-fluorouracil-epirubicin-cyclophosphamide, topotecan and etoposide were included in the analysis. The myelosuppression model was fitted to the data using NONMEM VI. IOV in the model parameters baseline neutrophil counts (ANC0), mean transit time through the non-mitotic maturation chain (MTT) and the parameter describing the concentration-effect relationship (Slope) were evaluated for statistical significance (P < 0.001).Results: IOV in MTT was significant for all the investigated datasets, except for topotecan, and was of similar magnitude (8-16 CV %). IOV in Slope was significant for docetaxel, topotecan and etoposide (19-39 CV %). For all six investigated datasets the IOV in myelosuppression parameters was lower than the IIV. There was no indication of systematic shifts in the system- or drug sensitivity-related parameters over time across data sets.Conclusion: This study indicates that the semi-physiological model of chemotherapy-induced myelosuppression has potential to be used for prediction of the time-course of myelosuppression in future courses and is thereby a valuable step towards individually tailored anticancer drug therapy.
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- Svane, G, et al.
(författare)
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Clinical experience of photon counting breast tomosynthesis: comparison with traditional mammography
- 2011
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 52:2, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- In two-dimensional mammography, a well-known problem is over- and underlying tissue which can either obstruct a lesion or create a false-positive result. Tomosynthesis, with an ability to layer the tissue in the image, has the potential to resolve these issues. Purpose To compare the diagnostic quality, sensitivity and specificity of a single tomosynthesis mammography image and a traditional two-view set of two-dimensional mammograms and to assess the comfort of the two techniques. Material and Methods One hundred and forty-four women, mainly chosen because of suspicious features on standard mammograms (76 malignant), had a single tomosynthesis image taken of one breast using a novel photon counting system. On average, the dose of the tomosynthesis images was 0.63 times that of the two-view images and the compression force during the procedure was halved. The resulting images were viewed by two radiologists and assessed both individually and comparing the two techniques. Results In 56% of the cases the radiologists rated the diagnostic quality of the lesion details higher in the tomosynthesis images than in the conventional images (and in 91% equal or higher), which means there is a statistically significant preference for the tomosynthesis technique. This included the calcifications which were rated as having better quality in 41% of the cases. While sensitivity was slightly higher for traditional mammography the specificity was higher for tomosynthesis. However, neither of these two differences was large enough to be statistically significant. Conclusion The overall accuracy of the two techniques was virtually equal despite the radiologist's very limited experience with tomosynthesis images and vast experience with two-dimensional mammography. As the diagnostic quality of the lesion details in the tomosynthesis images was valued considerably higher this factor should improve with experience. The patients also favored the tomosynthesis examination, rating the comfort of the procedure as much higher than regular mammography which might affect screening attendance.
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| 8. |
- Thorsmolle, Verner K., et al.
(författare)
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Conduction Through Viscoelastic Phase in a Redox-Active Ionic Liquid at Reduced Temperatures
- 2012
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Ingår i: Advanced Materials. - : Wiley. - 1521-4095 .- 0935-9648. ; 24:6, s. 781-781
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Tidskriftsartikel (refereegranskat)abstract
- The phase diagram of the redox active ionic liquid 1-methyl-3-propylimidazolium iodide (PMII) is examined as a function of temperature and iodine concentration. Beyond a threshold concentration of 3.9 M, the formation of higher polyiodides gives rise to a viscoelastic phase upon cooling. Despite of the very high viscosity of such polyiodide-containing PMII melts a strikingly high conductivity is maintained through Grotthuss-type bond exchange and ionic conduction.
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| 9. |
- Thorsmolle, Verner K., et al.
(författare)
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Extraordinarily Efficient Conduction in a Redox-Active Ionic Liquid
- 2011
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Ingår i: ChemPhysChem. - : Wiley. - 1439-7641 .- 1439-4235. ; 12:1, s. 145-149
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Tidskriftsartikel (refereegranskat)abstract
- Iodine added to iodide-based ionic liquids leads to extraordinarily efficient charge transport, vastly exceeding that expected for such viscous systems. Using terahertz time-domain spectroscopy, in conjunction with dc conductivity, diffusivity and viscosity measurements we unravel the conductivity pathways in 1-methyl-3-propylimidazolium iodide melts. This study presents evidence of the Grotthuss mechanism as a significant contributor to the conductivity, and provides new insights into ion pairing processes as well as the formation of polyiodides. The terahertz and transport results are reunited in a model providing a quantitative description of the conduction by physical diffusion and the Grotthuss bond-exchange process. These novel results are important for the fundamental understanding of conduction in molten salts and for applications where ionic liquids are used as charge-transporting media such as in batteries and dye-sensitized solar cells.
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