| 1. |
- Lecerof, David, et al.
(författare)
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Metal binding to Bacillus subtilis ferrochelatase and interaction between metal sites.
- 2003
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 8:4, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- Ferrochelatase, the terminal enzyme in heme biosynthesis, catalyses metal insertion into protoporphyrin IX. The location of the metal binding site with respect to the bound porphyrin substrate and the mode of metal binding are of central importance for understanding the mechanism of porphyrin metallation. In this work we demonstrate that Zn2+, which is commonly used as substrate in assays of the ferrochelatase reaction, and Cd2+, an inhibitor of the enzyme, bind to the invariant amino acids His183 and Glu264 and water molecules, all located within the porphyrin binding cleft. On the other hand, Mg2+, which has been shown to bind close to the surface at 7 Å from His183, was largely absent from its site. Activity measurements demonstrate that Mg2+ has a stimulatory effect on the enzyme, lowering KM for Zn2+ from 55 to 24 µM. Changing one of the Mg2+ binding residues, Glu272, to serine abolishes the effect of Mg2+. It is proposed that prior to metal insertion the metal may form a sitting-atop (SAT) complex with the invariant His-Glu couple and the porphyrin. Metal binding to the Mg2+ site may stimulate metal release from the protein ligands and its insertion into the porphyrin.
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| 2. |
- Thelander, Åsa, et al.
(författare)
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IKEA's image in three countries
- 2010
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Ingår i: Consuming IKEA; different perspectives on consumer images of a global retailer. - 9789185113422 ; , s. 111-130
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
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| 4. |
- Bjelke, Ulf, et al.
(författare)
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Mollusca : Blötdjur - Molluscs
- 2010
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Ingår i: The 2010 Red List of Swedish Species. Rödlistade arter i Sverige 2010. - Uppsala : ArtDatabanken, SLU. - 9789188506351 ; , s. 495-505
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
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| 6. |
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| 7. |
- Gertow, Karl, et al.
(författare)
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Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
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Tidskriftsartikel (refereegranskat)abstract
- Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
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| 8. |
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| 9. |
- Lund, Johan, et al.
(författare)
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Lenalidomide versus lenalidomide plus dexamethasone prolonged treatment after second-line lenalidomide plus dexamethasone induction in multiple myeloma
- 2018
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Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 7:6, s. 2256-2268
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Tidskriftsartikel (refereegranskat)abstract
- Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25mg/day) or Len+Dex (25mg/day and 40mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2years in the phase 2 trial were 47% versus 31% for Len versus Len+Dex (P = 0.14). After 36months median follow-up in surviving patients, median time to progression was not reached with Len+Dex and was 24.9months (95% confidence interval 12.5-not calculable, P amp;lt; 0.001) with Len. Three-year OS among the total observational study population was 61% (95% CI, 52-69%). The corresponding rate among patients who entered the phase 2 clinical trial was 73% (95% CI, 60-83%) and was significantly lower among those patients who achieved PR but did not proceed into the phase 2 trial (55%; P = 0.01). In the phase 2 trial, OS was 73% in both treatment arms (P = 0.70). Neutropenia and thrombocytopenia were more common with prolonged (phase 2 trial) versus short-term (observational study) Len administration but remained manageable. Prolonged treatment with Len with or without Dex provides sustained, clinically relevant responses and demonstrates an acceptable safety profile.
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| 10. |
- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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