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| 12. |
- Phillips, E., et al.
(författare)
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Compound specific isotope analysis in hydrogeology
- 2022
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 615
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Forskningsöversikt (refereegranskat)abstract
- Here, we review the contributions of Professor Barbara Sherwood Lollar to Compound Specific Isotope Analysis (CSIA) in contaminant hydrogeology and environmental chemistry. We first discuss the seminal work by Professor Sherwood Lollar's lab on establishing CSIA as a quantitative tool for contaminant (bio)transformation at contaminated groundwater sites. We describe the critical research by her lab in the development and validation of sample collection techniques, single- and multi-element CSIA, and isotope data evaluation for reliable interpretations. We highlight the contributions of Professor Sherwood Lollar's lab towards the development of best practices for the successful application of CSIA by industry to demonstrate the occurrence of (bio)transformation, identify (bio)transformation mechanisms, quantify the extent and rate of degradation and differentiate among potential contaminant sources. We then explore Professor Sherwood Lollar's applications of CSIA to hydrogeology of the deep subsurface and the fast widening of the field to new environments (e.g., sediments), contaminants (e.g., chlorofluorocarbons, pesticides), and systems (e.g., plant, enzymes).
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| 17. |
- Hov, J. R., et al.
(författare)
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Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis
- 2011
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 53:6, s. 1967-1976
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Tidskriftsartikel (refereegranskat)abstract
- The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976)
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| 20. |
- Lindstrom, L., et al.
(författare)
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Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:3, s. 297-304
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The risk for recurrent primary sclerosing cholangitis (rPSC) after liver transplantation is associated with inflammatory bowel disease (IBD). We assessed the frequency of rPSC and studied risk factors for recurrent disease with special focus on IBD. We also evaluated the importance of rPSC for prognosis.Materials and methods: All liver transplanted PSC patients in the Nordic countries between 1984 and 2007 (n=440), identified by the Nordic Liver Transplant Registry, were studied. Data were retrieved from patients' chart reviews. Multivariable Cox regression models were used to calculate risk factors for rPSC and death.Results: Of the 440 patients with a follow-up time after liver transplantation of 3743 patient years, rPSC was diagnosed in 19% (n=85). Colectomy before liver transplantation was associated with a reduced risk of rPSC (HR 0.49; 95% CI, 0.26-0.94, p=0.033). Neither high IBD activity nor presence of IBD flares before or after liver transplantation was associated with rPSC. Treatment with tacrolimus was an independent risk factor associated with increased risk for rPSC (HR, 1.81; 95% CI, 1.15-2.86, p=0.010). The risk of dying or needing a re-transplantation after rPSC was increased in all age groups, but highest in patients transplanted before 40 years of age (HR 7.3; 95% CI, 4.1-12.8, p=0.0001).Conclusions: This study confirms that colectomy before liver transplantation is associated with a decreased risk of rPSC. Inflammatory activity of IBD was not associated with the risk of rPSC. Tacrolimus was an independent risk factor for PSC recurrence and its use as first line immunosuppression in PSC needs further study.
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