| 1. |
- Abelein, Axel, et al.
(författare)
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Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:32, s. 23518-23528
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Tidskriftsartikel (refereegranskat)abstract
- Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state.
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| 2. |
- Albin, Maria, et al.
(författare)
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Astma och eksem hos frisörer.
- 1998
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Ingår i: Hygiea. - 0346-6264. ; 1:Band 107:144, s. 137-137
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Konferensbidrag (refereegranskat)
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| 3. |
- Albin, Maria, et al.
(författare)
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Incidence of asthma in female Swedish hairdressers.
- 2002
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 59:2, s. 119-23.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the risk of asthma in hairdressers. METHODS: The incidence of asthma was retrospectively estimated in a Swedish nationwide study including all female hairdressers certified from vocational schools from 1970 to 1995, and a stratified sample of women from the general population were referents. A postal questionnaire included questions on respiratory tract symptoms, atopy, smoking, working periods as a hairdresser, and number of specific hair treatments performed/week. Reported exposures were validated by occupational hygienists. Rate ratios of incidence (IRRs) of asthma were estimated by Poisson regression, adjusted for calendar year of observation, hay fever, smoking, and region of domicile. RESULTS: The crude incidences of asthma/1000 person-years were: 3.9 during active years as a hairdresser, 2.8 among the hairdressers when not working in the profession, and 3.1 among the referents. The corresponding IRR for being an active hairdresser compared with the referents was 1.3 (95% confidence interval (95% CI) 1.0 to 1.6). Moderate effects on risk of asthma were found both from hairdressing work (IRR=1.6 (1.1 to 2.2) among never-smokers) and from smoking (IRR=1.6 (1.2 to 2.2) among referents). However, the combined effect from hairdressing work and smoking (IRR=1.5 (1.0 to 2.1)) was less than expected (p=0.02). No effect modification by respiratory atopy was found. The hairdressers most often performing hair bleaching treatments (IRR=1.5 (0.7 to 3.0)) or using hair spray (IRR=1.4 (0.8 to 2.4)) had, compared with the most infrequent users, a slightly, but not significantly higher incidence of asthma. Exposure to persulphates in hair bleach was estimated to be 0.04-0.15 mg/m(3) during mixing of the powder. Reported average number of bleaching treatments agreed well with those performed according to a diary. CONCLUSIONS: Active hairdressing work was associated with a moderately increased incidence of asthma among lifelong non-smokers. The results are moderately supportive, but not conclusive, of associations between asthma and exposure to hair bleach or hair spray.
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| 4. |
- Ali, Neserin, et al.
(författare)
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Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
- 2018
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Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.
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| 5. |
- Andersen, Christina, et al.
(författare)
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Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study
- 2018
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Ingår i: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
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Konferensbidrag (refereegranskat)abstract
- We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
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| 6. |
- Andersen, Christina, et al.
(författare)
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Inhalation and Dermal Uptake of Particle and Gas-phase Phthalates - A Human Exposure Study
- 2018
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 52:21, s. 12792-12800
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labelled airborne phthalates: particle-phase D4-DEHP (di-(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone, and combined inhalation+dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014±0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 hour exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation+dermal was 0.0067±0.0045 and 0.00073±0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles, and highlights the importance of considering the deposited dose in particle uptake studies.
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| 7. |
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| 8. |
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| 9. |
- Barbateskovic, Marija, et al.
(författare)
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A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions
- 2021
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 135, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.
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| 10. |
- Bergholdt, R, et al.
(författare)
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Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 8:3, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.
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