| 21. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 22. |
- Garkavij, Michael, et al.
(författare)
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Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats
- 1994
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Ingår i: Journal of nuclear biology and medicine (Turin, Italy : 1991). - 0368-3249. ; 38:4, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.
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| 23. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets
- 2017
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 18:4, s. 305-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. Methods: The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. Results: Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV-1 RNA copies/mL. Conclusions: The 2014 UNAIDS/WHO 90-90-90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals.
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| 24. |
- Håkansson, H., et al.
(författare)
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In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds
- 1991
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 69:6, s. 459-471
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Tidskriftsartikel (refereegranskat)abstract
- Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOCl) in the matrices tested. In some test systems, the specimens with a higher EOCl concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOCl content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus anlagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOCl concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOCl content, were of low toxicity, and the observed effects need to be verified in future studies.
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| 25. |
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| 26. |
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| 27. |
- Lindman, J., et al.
(författare)
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Diabetes and pre-diabetes among police officers in Guinea-Bissau
- 2017
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Ingår i: African Journal of Diabetes Medicine. - 2042-8545. ; 25:2, s. 19-20
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Tidskriftsartikel (refereegranskat)abstract
- This study has investigated the prevalence of type 2 diabetes among 1119 police officers in Guinea-Bissau. Those with a random blood glucose (RBG) > 8.0 mol/l had HbA1c (glycated haemoglobin) testing. Diabetes (HbA1c > 6.5%) was present in 4.1%, and pre-diabetes (HbA1c 5.7-6.5%) was present in a further 4.2%. Factors associated with diabetes were age, weight and ethnicity.
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| 28. |
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