| 1. |
- Ekström, Ulf, et al.
(författare)
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An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
- 1999
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
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| 2. |
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| 3. |
- Nilsson, Henrik, et al.
(författare)
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Monte Carlo simulations of the light interaction with blood vessels in human skin in the red wavelength region
- 1998
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Ingår i: Proceedings of SPIE, 3252(06),44-53. - San José : SPIE. - 9780819426918 ; , s. 44-53
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Konferensbidrag (refereegranskat)abstract
- An attempt was made at determining if the elastically backscattered Doppler shifted light from cutaneous blood vessels merely emanates from the peripheral parts, or also from the more central core of these vessels, after illumination by red laser light (632 nm). A multilayered, semi-infinite Monte Carlo model of human skin was constructed accordingly, with separate layers or epidermis, dermis including blood, inferior vascular plexus and subcutaneous fat. Two concentric cylinders of infinite length and with varying diameters, representing core and peripheral parts of a blood vessel, were located at various depths in the skin model, either in the superior or inferior vascular plexus. In order to test the stability of the model predictions, widely varying values of the optical properties were employed in the calculations, trying to encompass most of the extreme values found in the literature. The number of photons Doppler shifted by a fixed size central core of a small blood vessel, is independent of the volume of blood surrounding this core in the rest of the blood vessel, provided the total number of detected photons is maintained constant, and the vessel dimensions are within human physiological limits. For the source/detector system simulated (one optical fiber 700 micrometer diameter), backscattered light Doppler shifted in superficial blood vessels constituted almost all the photons detected, with only very few photons having interacted with the inferior plexus.
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| 5. |
- Ejlertsson, Jörgen, et al.
(författare)
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Anaerobic Degradation of Nonylphenol Mono- and Diethoxylates in Digestor Sludge, Landfilled Municipal Solid Waste, and Landfilled Sludge
- 1999
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 1086-931X .- 1520-6912 .- 0013-936X .- 1520-5851. ; 33:2, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the extent to which anaerobic digestor sludge, landfilled sludge, and landfilled municipal solid waste (MSW) degrade NPEOs under methanogenic conditions. NPEO1 and NPEO2 (NPEO1-2), used in a mixture, were chosen as model compounds. Anaerobic experimental bottles were amended with 100% digestor sludge at three different concentrations of NPEO1-2: 2, 60, and 308 mg L-1. [U-14C]-NPEO1-2 was used to detect any possible decomposition of the aromatic moiety of the NPEO1-2. All inoculates used degraded NPEO1-2 at 2 mg L-1, with nonylphenol (NP) forming the ultimate degradation product. The NP formed was not further degraded, and the incubations with labeled NPEO showed that the aromatic structure remained intact. Both landfill inoculates also transformed NPEO1-2 at 60 mg L-1. CH4 production was temporarily hampered in bottles with MSW landfill inoculum at 60 and 308 mg L-1. With 2 mg L-1 of NPEO, CH4 production closely followed that in the controls. Both NP and NPEO1-2 interacted with the organic matter which resulted in sorption to the solid phase.
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| 6. |
- Ekström, Ulf, et al.
(författare)
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Mutations in the low-density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response
- 1998
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 28:9, s. 740-747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
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| 10. |
- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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Butylated hydroxytoluene and N-acetylcysteine attenuates tumor necrosis factor-alpha (TNF-alpha) secretion and TNF-alpha mRNA expression in alveolar macrophages from human lung transplant recipients in vitro
- 1998
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Ingår i: Transplantation. - 0041-1337. ; 66:3, s. 364-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a polypeptide cytokine principally produced by macrophages/monocytes and commonly associated with inflammatory conditions. The present study was designed to investigate whether the antioxidants butylated hydroxytoluene (BHT) and N-acetylcysteine (NAC) modified TNF-alpha production in stimulated and unstimulated alveolar macrophages from lung transplant recipients in vitro. METHODS: The effects of BHT and NAC on TNF-alpha production were studied both with and without lipopolysaccharide (LPS) activation of alveolar macrophages from bronchoalveolar lavage fluid. TNF-alpha was quantitated in cell culture medium using an enzyme-linked immunosorbent assay. TNF-alpha mRNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction on total RNA extracted from the incubated alveolar macrophages. RESULTS: In unstimulated alveolar macrophages, TNF-alpha levels were significantly reduced by incubation with BHT or NAC. When alveolar macrophages from patients with cytomegalovirus infection were incubated with BHT, TNF-alpha secretion was significantly lowered. A significant reduction of TNF-alpha levels in LPS-stimulated alveolar macrophages was obtained in the presence of BHT or NAC. Our data from quantitative reverse transcription-polymerase chain reaction showed that the observed decrease in protein levels of TNF-alpha was associated with a decrease in TNF-alpha mRNA expression. CONCLUSIONS: Our results indicate that antioxidant treatment may be an effective step to lower the inflammatory process caused by cytomegalovirus infection or in endotoxin (LPS)-activated macrophages. The therapeutic use of antioxidant compounds could, therefore, be of interest in conditions such as lung transplantation, in which oxidative stress and inflammation can contribute significantly to the loss of allograft function.
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