| 1. |
|
|
| 2. |
|
|
| 3. |
- Englund, Mikael C. O., 1971
(författare)
-
Regulation of human macrophage gene expression by oxidized low density lipoprotein. Studies on tumor necrosis factor-a and global gene expression profiles
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a multifactorial and progressive disease that is characterized by a focal thickening of the arteries caused by accumulation of lipoproteins, extracellular matrix, and the migration and proliferation of various cell types. Among the cells found in atherosclerotic lesions are macrophages, which accumulate lipids and are transformed into foam cells. The atherosclerotic lesion is also characterized as a site of inflammation. In vivo and in vitro data support the role of macrophages in the development of an inflammatory response in the vessel wall. Several pro-inflammatory cytokines have been detected in the atherosclerotic plaque, among those are tumor necrosis factor-a (TNF-a). Major sources of TNF-a are activated macrophages. Macrophages have been connected to expression of several cytokines in the atherosclerotic plaque that can modulate plaque development.Oxidative modification of lipoproteins is regarded as a key event in the development of atherosclerosis. The oxidation of the low density lipoprotein (LDL) particle produces several biologically active molecules. Among the products formed are oxysterols, which are found in atherosclerotic plaques. Oxysterols have been implicated in the development of atherosclerosis. The main aim of this thesis was to investigate the impact of oxidized LDL (oxLDL) and oxysterols on gene expression in human macrophages.The results obtained in this thesis demonstrate that oxLDL and oxysterols, in particular 25-hydroxyxcholesterol (25-OH), modulates expression of TNF-a. OxLDL decreased the lipopolysaccharide (LPS)-induced DNA binding of the transcription factor nuclear factor kappaB (NF-kB) to the TNF-a promoter. This suggests that oxLDL can decrease the inflammatory response in macrophages. Further, it was demonstrated that 25-OH could decrease an LPS-induced TNF-a secretion, but also that 25-OH together with interferon-gamma (IFN-g) could contribute to an increased expression of TNF-a. 25-OH affects both transcriptional and post-transcriptional events including kinase activity, and also intracellular levels of H2O2 that could influence gene expression. Microarray experiments suggest that oxLDL induces a coordinated stress response, activates detoxification enzymes, as well as the more expected changes in lipid and cholesterol metabolism in macrophages.In conclusion, this thesis shows that components of oxLDL can influence expression of genes in macrophages, which could contribute to the development of atherosclerosis.
|
|
| 4. |
-
Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients : a prospective study
- 2001
-
Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 47:1, s. 43-50
-
Tidskriftsartikel (refereegranskat)abstract
- The frequency of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CdAD) was prospectively determined in a population of 2462 patients recruited from five Swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. AAD developed in 4.9% of the treated patients. Faecal samples were obtained from 69% of patients with AAD and 55.4% were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9% at the participating centres (P < 0.001). The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units (6.7 and 7.1%, respectively). There was no difference in frequency of AAD when analysed with respect to gender or age. Medical interventions (laxative treatment, endoscopy and abdominal surgery) or presence of one concomitant disease (diabetes, malignancy, chronic renal disease and inflammatory bowel disease) did not significantly affect the frequency of AAD, whereas patients suffering from two or more of these illnesses had significantly (P = 0.001) higher frequencies of AAD. Patients treated with antibiotics for 3 days had a significantly (P = 0.009) lower frequency of AAD than those treated for longer periods. Treatment with cephalosporins, clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD. With specimens from one centre, 62.5% of tested patients with AAD and 33.8% of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool samples was significantly associated with AAD IP = 0.003), the causal relationship with diarrhoea is not always evident.
|
|
| 5. |
- Hansson, Mattias, et al.
(författare)
-
Artifactual insulin release from differentiated embryonic stem cells.
- 2004
-
Ingår i: Diabetes. - 0012-1797. ; 53:10, s. 2603-9
-
Tidskriftsartikel (refereegranskat)abstract
- Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.
|
|
| 6. |
- Heins, Nico, et al.
(författare)
-
Derivation, characterization, and differentiation of human embryonic stem cells.
- 2004
-
Ingår i: Stem cells (Dayton, Ohio). - 1066-5099. ; 22:3, s. 367-76
-
Tidskriftsartikel (refereegranskat)abstract
- The derivation of human embryonic stem (hES) cells establishes a new avenue to approach many issues in human biology and medicine for the first time. To meet the increased demand for characterized hES cell lines, we present the derivation and characterization of six hES cell lines. In addition to the previously described immunosurgery procedure, we were able to propagate the inner cell mass and establish hES cell lines from pronase-treated and hatched blastocysts. The cell lines were extensively characterized by expression analysis of markers characteristic for undifferentiated and differentiated hES cells, karyotyping, telomerase activity measurement, and pluripotency assays in vitro and in vivo. Whereas three of the cell lines expressed all the characteristics of undifferentiated pluripotent hES cells, one cell line carried a chromosome 13 trisomy while maintaining an undifferentiated pluripotent state, and two cell lines, one of which carried a triploid karyotype, exhibited limited pluripotency in vivo. Furthermore, we clonally derived one cell line, which could be propagated in an undifferentiated pluripotent state.
|
|
| 7. |
- Mittelholzer, C., et al.
(författare)
-
Detection and Sequence Analysis of Danish and Swedish Strains of Mink Astrovirus
- 2003
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 41:11, s. 5192-5194
-
Tidskriftsartikel (refereegranskat)abstract
- The sequences of mink astroviruses collected from 11 farms in Denmark and Sweden were analyzed and found to be homologous with one another but different from those of other astroviruses. A species-specific reverse transcriptase-PCR for mink astrovirus was established and shown to be suitable for the analysis of clinical samples.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Svensson, Per-Arne, 1969, et al.
(författare)
-
Copper induces the expression of cholesterogenic genes in human macrophages.
- 2003
-
Ingår i: Atherosclerosis. - 0021-9150. ; 169:1, s. 71-6
-
Tidskriftsartikel (refereegranskat)abstract
- Accumulation of lipids and cholesterol by macrophages and subsequent transformation into foam cells are key features in development of atherosclerosis. Serum copper concentrations have been shown to be associated with cardiovascular disease. However, the mechanism behind the proatherogenic effect of copper is not clear. We used DNA microarrays to define the changes in gene expression profile in response to copper exposure of human macrophages. Expression monitoring by DNA microarray revealed 91 genes that were regulated. Copper increased the expression of seven cholesterogenic genes (3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase, IPP isomerase, squalene synthase, squalene epoxidase, methyl sterol oxidase, H105e3 mRNA and sterol-C5-desaturase) and low-density lipoprotein receptor (LDL-R), and decreased the expression of CD36 and lipid binding proteins. The expression of LDL-R and HMG CoA reductase was also investigated using real time PCR. The expression of both of these genes was increased after copper treatment of macrophages (P<0.01 and P<0.01, respectively). We conclude that copper activates cholesterogenic genes in macrophages, which may provide a mechanism for the association between copper and atherosclerosis. The effect of copper on cholesterogenic genes may also have implications for liver steatosis in early stages of Wilson's disease.
|
|
