| 1. |
- Bosson, Jenny, et al.
(författare)
-
Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects
- 2003
-
Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 33:6, s. 777-782
-
Tidskriftsartikel (refereegranskat)abstract
- Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group. Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility. Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78. Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects. Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.
|
|
| 2. |
|
|
| 3. |
- Albers, Eva, 1966, et al.
(författare)
-
Ser3p (Yer081wp) and Ser33p (Yil074cp) are phosphoglycerate dehydrogenases in Saccharomyces cerevisiae
- 2003
-
Ingår i: J Biol Chem. ; 278, s. 10264-10272
-
Tidskriftsartikel (refereegranskat)abstract
- Two genes YER081W and YIL074C, renamed SER3 and SER33, respectively, which encode phosphoglycerate dehydrogenases in Saccharomyces cerevisiae were identified. These dehydrogenases catalyze the first reaction of serine and glycine biosynthesis from the glycolytic metabolite 3-phosphoglycerate. Unlike either single mutant, the ser3Delta ser33Delta double mutant lacks detectable phosphoglycerate dehydrogenase activity and is auxotrophic for serine or glycine for growth on glucose media. However, the requirement for the SER-dependent "phosphoglycerate pathway" is conditional since the "glyoxylate" route of serine/glycine biosynthesis is glucose-repressed. Thus, in cells grown on ethanol both expression and activity of all SER-encoded proteins are low, including the remaining enzymes of the phosphoglycerate pathway, Ser1p and Ser2p. Moreover the available nitrogen source regulates the expression of SER genes. However, for only SER33, and not SER3, expression was regulated in relation to the available nitrogen source in a coordinated fashion with SER1 and SER2. Based on these mRNA data together with data on enzyme activities, Ser33p is likely to be the main isoenzyme of the phosphoglycerate pathway during growth on glucose. Moreover, since phosphoglycerate dehydrogenase activity requires NAD+ as cofactor, deletion of SER3 and SER33 markedly affected redox metabolism as shown by substrate and product analysis.
|
|
| 4. |
- Bengtsson, Anders, et al.
(författare)
-
Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies
- 2000
-
Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 9:9, s. 664-671
-
Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.
|
|
| 5. |
- Blomberg, Marie, 1963-, et al.
(författare)
-
Congenital malformations in the southeast of Sweden : a registry study with validation
- 2000
-
Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 89:10, s. 1238-1243
-
Tidskriftsartikel (refereegranskat)abstract
- A study was made of the occurrence of congenital malformations in the southeast region of Sweden, utilizing all available relevant health registries. Östergötland county had been pinpointed in a routine surveillance as having an increased malformation risk. Various validations of the register data were undertaken and different types of errors were detected. An increased risk was seen, in Östergötland county compared to the reference counties, for specific types of malformations: preauricular appendices, pylorostenosis, uterine/vaginal malformations, foot deformities, limb reduction defects and cardiovascular malformations. Variable classification or registration artefacts explained the excess among the first four conditions. Limb reduction defects were also mis-coded, but the increased risk in Östergötland county may persist.Conclusion: There is an increased risk of major cardiovascular malformations in Östergötland county compared to the reference counties that also shows an uneven distribution within the county.
|
|
| 6. |
- Caesar, Robert, 1973, et al.
(författare)
-
The stress-induced Tfs1p requires NatB-mediated acetylation to inhibit carboxypeptidase Y and to regulate the protein kinase A pathway
- 2004
-
Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 279:37, s. 38532-38543
-
Tidskriftsartikel (refereegranskat)abstract
- The Saccharomyces cerevisiae N-terminal acetyltransferase NatB consists of the subunits Nat3p and Mdm20p. We found by two-dimensional PAGE analysis that nat3{Delta} exhibited protein expression during growth in basal medium resembling protein expression in salt-adapted wild-type cells. The stress-induced carboxypeptidase Y (CPY) inhibitor and phosphatidylethanolamine-binding protein family member Tfs1p was identified as a novel NatB substrate. The N-terminal acetylation status of Tfs1p, Act1p, and Rnr4p in both wild type and nat3{Delta} was confirmed by tandem mass spectrometry. Furthermore it was found that unacetylated Tfs1p expressed in nat3{Delta} showed an ~100-fold decrease in CPY inhibition compared with the acetylated form, indicating that the N-terminal acetyl group is essential for CPY inhibition by Tfs1p. Phosphatidylethanolamine-binding proteins in other organisms have been reported to be involved in the regulation of cell signaling. Here we report that a number of proteins, whose expression has been shown previously to be dependent on the activity in the protein kinase A (PKA) signaling pathway, was found to be regulated in line with low PKA activity in the nat3{Delta} strain. The involvement of Nat3p and Tfs1p in PKA signaling was supported by caffeine growth inhibition studies. First, growth inhibition by caffeine addition (resulting in enhanced cAMP levels) was suppressed in tfs1{Delta}. Second, this suppression by tfs1{Delta} was abolished in the nat3{Delta} background, indicating that Tfs1p was not functional in the nat3{Delta} strain possibly because of a lack of N-terminal acetylation. We conclude that the NatB-dependent acetylation of Tfs1p appears to be essential for its inhibitory activity on CPY as well its role in regulating the PKA pathway
|
|
| 7. |
- Eriksson, Peter, et al.
(författare)
-
Rap1p-binding sites in the saccharomyces cerevisiae GPD1 promoter are involved in its response to NaCl.
- 2000
-
Ingår i: The Journal of biological chemistry. - 0021-9258. ; 275:38, s. 29368-76
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanisms involved in transcriptional regulation of the osmotically controlled GPD1 gene in Saccharomyces cerevisiae were investigated by promoter analysis. The GPD1 gene encodes NAD(+)-dependent glycerol-3-phosphate dehydrogenase, a key enzyme in the production of the compatible solute glycerol. By analysis of promoter deletions, we identified a region at nucleotides -478 to -324, in relation to start of translation, to be of great importance for both basal activity and osmotic induction of GPD1. Electrophoretic mobility shift and DNase I footprint analyses demonstrated protein binding to parts of this region that contain three consensus sequences for Rap1p (repressor activator protein 1)-binding sites. Actual binding of Rap1p to this region was confirmed by demonstrating enhanced electrophoretic mobility of the protein-DNA complex with extracts containing an N-terminally truncated version of Rap1p. The detected Rap1p-DNA interactions were not affected by changes in the osmolarity of the growth medium. Specific inactivation of the Rap1p-binding sites by a C-to-A point mutation in the core of the consensus showed that this factor is a major determinant of GPD1 expression since mutations in all three putative binding sites for Rap1p strongly hampered osmotic induction and drastically lowered basal activity. We also show that the Rap1p-binding sites appear functionally distinct; the most distal site (core of the consensus at position -386) exhibited the highest affinity for Rap1p and was strictly required for low salt induction (< or =0.6 m NaCl), but not for the response at higher salinities (> or =0.8 m NaCl). This indicates tha different molecular mechanisms might be operational for low and high salt responses of the GPD1 promoter.
|
|
| 8. |
- Filén, Finn, et al.
(författare)
-
Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions
- 2004
-
Ingår i: Sexually Transmitted Diseases. - 0148-5717 .- 1537-4521. ; 31:6, s. 331-6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A sensitive and specific method for detecting herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) is important for diagnosing genital and cutaneous infections. GOAL: The goal of this study was to compare quantitative real-time polymerase chain reaction (qPCR) with virus culture for diagnosis of genital and cutaneous HSV-1 and HSV-2. STUDY DESIGN: A duplex qPCR system for quantification of DNA from HSV-1 and HSV-2 was developed. Duplicate swabs for PCR and virus culture were collected from 89 patients attending our sexually transmitted infection and dermatology clinic. RESULTS: The duplex qPCR had a linear measure interval of 10-10 copies/mL. The detection limit was between 1 and 5 copies per reaction. qPCR detected HSV in 57 (64%) specimens and virus was isolated in 45 (50%) cases. First-episode infections showed higher viral quantities with a median value of 4.2 x 10 copies per reaction compared with recurrent infections with 1.0 x 10 (P = 0.0002). HSV-1 was more likely to be the cause of first-episode genital infections (72%), and HSV-2 of recurrent and atypical genital manifestations (73%). CONCLUSION: Real-time PCR is a sensitive method for diagnosing genital herpes, and the duplex format is convenient for typing. The method increased the detection rate by 27% compared with virus culture.
|
|
| 9. |
|
|
| 10. |
- Gustafsson, John, 1975, et al.
(författare)
-
Statistical exploration of variation in quantitative two-dimensional gel electrophoresis
- 2004
-
Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 4:12, s. 3791-3799
-
Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional gel electrophoresis is a major technique in global analysis at the protein level. This paper presents an examination of spot volume data from three gel sets with radioactively labeled yeast Saccharomyces cerevisiae proteins. A strong variance versus mean dependence in data was found to be stabilized by applying a shifted logarithmic transformation. However, transformed data showed a remaining substantial variance heterogeneity for different proteins. Furthermore, examination of studentized residuals revealed that transformed data were approximately normally distributed and that there were spatial correlations among the measurement errors in the gel.
|
|
