| 1. |
- Widell, Anders, et al.
(författare)
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Antibody to a hepatitis C virus related protein among patients at high risk for hepatitis B
- 1991
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 23:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Anti-HCV prevalence in treated hemophiliacs, their heterosexual partners, intravenous drug addicts and homosexual men was studied. In hemophiliacs and many of the intravenous drug addicts, greater than or equal to 2 sera drawn 1-18 or 1-17 years apart were available. Anti-HCV testing was performed by ELISA (Ortho). Among patients with severe and moderate hemophilia A, 87% (98/112) were positive for anti-HCV at least once and among patients with severe and moderate hemophilia B, 83% (24/29) were positive for anti-HCV. Seroconversion to anti-HCV was observed in 21% of hemophilia patients. In hemophilia A, HCV infection generally occurred during the first years of life and in hemophilia B somewhat later. Loss of anti-HCV antibody was seen in 12% (17 patients). The rest, 54% (76 patients) were seropositive in first and last samples. All 12 tested spouses to anti-HCV positive men were anti-HCV negative. 80% of the drug addicts (137/172) were seropositive for anti-HCV. In those with greater than 1 serum tested, 8% were consistently negative and 68% consistently positive. 21% seroconverted to anti-HCV while 3% lost antibody. 10% (22/211) of homosexual men were anti-HCV positive. Intravenous transmission of HCV thus seemed highly efficient whereas sexual transmission was much less efficient.
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| 2. |
- Aneheim, Emma, 1982, et al.
(författare)
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Behaviour, use and safety aspects of astatine-211 solvated in chloroform after dry distillation recovery
- 2024
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Ingår i: SCIENTIFIC REPORTS. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Targeted alpha therapy of disseminated cancer is an emerging technique where astatine-211 is one of the most promising candidate nuclides. Astatine-211 can be produced in medium energy cyclotrons by alpha particle bombardment of natural bismuth. The produced astatine is then commonly recovered from the irradiated solid target material through dry distillation. The dry distillation process often includes elution and solvation of condensed astatine with chloroform, forming Chloroform Eluate. In this work the handling and safe use of the high activity concentration Chloroform Eluate has been investigated. Correctly performed, evaporation of Chloroform Eluate results in a dry residue with complete recovery of the astatine. The dry residue can then serve as a versatile starting material, using appropriate oxidizing or reducing conditions, for subsequent downstream chemistry. However, it has been found that when evaporating the Chloroform Eluate, astatine can be volatilized if continuing the process beyond the point of dryness. This behavior is more pronounced when the Chloroform Eluate has received a higher absorbed dose. Upon water phase contact of the Chloroform Eluate, a major part of the astatine activity becomes water soluble, leaving the organic phase. A behavior which is also dependent on dose to the solvent.
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| 3. |
- Asad, Samina, et al.
(författare)
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HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
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| 4. |
- Bandick, Roger, 1974-
(författare)
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Multinationals, employment and wages : microeconomic evidence from Swedish manufacturing
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis, consisting of four essays, is to study the effects of multinationals and inward FDI on employment and wage formation in Swedish manufacturing during the 1990s. Paper [1] (co-authored with Patrik Karpaty) investigates the employment effects of foreign acquisitions in acquired firms in Swedish manufacturing during the 1990s. To handle likely endogeneity problems we evaluate the effects of foreign acquisitions on the targeted firms’ employment by combining propensity score matching with difference-in-difference estimation. We find some evidence of positive employment effects in firms taken over by foreigners and it seems that the employment of skilled labor increases more than that of less-skilled labor. Moreover, we examine whether the employment impact of foreign ownership differs between takeovers of Swedish MNEs and non-MNEs. Our results indicate that the positive employment effects only appear in acquired non-MNEs. Furthermore, we observe shifts in skill intensities toward higher shares of skilled labor in non-MNEs taken over by foreign MNEs, but not in acquired Swedish MNEs. Paper [2] (co-authored with Pär Hansson) investigates whether the increased foreign ownership in Sweden in the 1990s have had any effects on relative demand for skilled labor. Estimating relative labor demand at the firm level and using propensity score matching with difference-in-difference estimation, we obtain support for relative demand for skilled labor tending to rise in non-multinationals (non-MNEs) but not in multinationals (MNEs) that become foreign owned. Other interesting findings are that a larger presence of foreign MNEs in an industry appears to have a positive impact on the relative demand for skills in Swedish MNEs within the same industry and that the elasticity of substitution between skilled and less-skilled labor seems to be lower in MNEs than in non-MNEs. Paper [3] investigates whether MNEs are more likely than non-MNEs to close down their plants, due to their footloose character. The results from using a panel of all Swedish manufacturing plants over the period 1993 and 2002 suggest that MNE plants, and in particular Swedish MNE plants, have a higher probability of exiting the market than non-MNE plants. The outcome is robust controlling for other variables affecting the survival rates. Among non-MNE plants, the probabilities of exit are higher in non-exporting firms than in exporting firms. Moreover, the increased foreign presence in Swedish manufacturing seems, due to intensified competition, to have led to the higher exit rates of plants in non-exporting non-MNEs. Plants of globally engaged indigenous firms, such as plants of Swedish MNEs and exporting non-MNEs, appear, on the other hand, to have been unaffected by the increased foreign presence. Paper [4] examines whether MNEs Swedish MNEs and foreign-owned firms pay higher wages than non-MNEs in manufacturing, controlling for firm heterogeneity and individual characteristics. In accordance with the idea that MNEs are superior in performance to other firms, I find that MNEs pay higher wages than non-MNEs, in particular for skilled labor. Yet the MNE wage premium is low; the average wages in MNEs are between 4-7 percent higher than in non-MNEs, while estimates at the individual level reduce the wage premium in MNEs to around 2-3 percent. Higher wages in foreign-owned firms may result from foreign acquisitions of high-wage firms. Alternatively, the acquired firms might have a more favorable wage growth than non-targeted domestically owned firms. My findings only lend support to the hypothesis that foreign firms select high-wage firms (especially non-MNEs) for acquisition.
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| 5. |
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| 6. |
- Dekker Nitert, Marloes, et al.
(författare)
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Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes.
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797.
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Tidskriftsartikel (refereegranskat)abstract
- To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH(+)) or without (FH(-)) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH(+) compared with FH(-) men. We further validated our findings from FH(+) men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH(+) men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH(+) and FH(-) individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P < 3 × 10(-6)) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIB1, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome.
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| 7. |
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| 8. |
- El Fakiri, Mohamed, et al.
(författare)
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Development and Preclinical Evaluation of [211At]PSAt-3-Ga: An Inhibitor for Targeted a-Therapy of Prostate Cancer
- 2024
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Ingår i: JOURNAL OF NUCLEAR MEDICINE. - 0161-5505 .- 1535-5667. ; 65:4, s. 593-599
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Tidskriftsartikel (refereegranskat)abstract
- The application of prostate -specific membrane antigen (PSMA)- targeted a -therapy is a promising alternative to b 2 -particle-based treatments. 211 At is among the potential a -emitters that are favorable for this concept. Herein, 211 At-based PSMA radiopharmaceuticals were designed, developed, and evaluated. Methods: To identify a 211 At-labeled lead, a surrogate strategy was applied. Because astatine does not exist as a stable nuclide, it is commonly replaced with iodine to mimic the pharmacokinetic behavior of the corresponding 211 At-labeled compounds. To facilitate the process of structural design, iodine -based candidates were radiolabeled with the PET radionuclide 68 Ga to study their preliminary in vitro and in vivo properties before the desired 211 At-labeled lead compound was formed. The most promising candidate from this evaluation was chosen to be 211 At-labeled and tested in biodistribution studies. Results: All 68 Ga-labeled surrogates displayed affinities in the nanomolar range and specific internalization in PSMA-positive LNCaP cells. PET imaging of these compounds identified [ 68 Ga]PSGa- 3 as the lead compound. Subsequently, [ 211 At]PSAt- 3 -Ga was synthesized in a radiochemical yield of 35% and showed tumor uptake of 19 +/- 8 percentage injected dose per gram of tissue (%ID/g) at 1 h after injection and 7.6 +/- 2.9 %ID/g after 24 h. Uptake in off -target tissues such as the thyroid (2.0 +/- 1.1 %ID/g), spleen (3.0 +/- 0.6 %ID/g), or stomach (2.0 +/- 0.4 %ID/g) was low, indicating low in vivo deastatination of [ 211 At]PSAt- 3 -Ga. Conclusion: The reported findings support the use of iodine -based and 68 Ga-labeled variants as a convenient strategy for developing astatinated compounds and confirm [ 211 At]PSAt- 3 as a promising radiopharmaceutical for targeted a -therapy.
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| 9. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 10. |
- Grönwall, Caroline, et al.
(författare)
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A Comprehensive Evaluation of the Relationship Between Different IgG and IgA Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the "Cit-umbrella" similar to ACPA fine-specificities, while MAA reactivity is distinctly different.
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