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| 2. |
- Albin, Maria, et al.
(författare)
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Retention patterns of asbestos fibres in lung tissue among asbestos cement workers
- 1994
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Ingår i: Occupational and Environmental Medicine. - 1470-7926. ; 51:3, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- Retention patterns in lung tissue (determined by transmission electron microscopy and energy dispersive spectrometry) of chrysotile, tremolite, and crocidolite fibres were analysed in 69 dead asbestos cement workers and 96 referents. There was an accumulation of tremolite with time of employment. Among workers who died within three years of the end of exposure, the 13 with high tremolite concentrations had a significantly longer duration of exposure than seven in a low to intermediate category (medians 32 v 20 years; p = 0.018, one sided). Crocidolite showed similar patterns of accumulation. In workers who died more than three years after the end of exposure, there were no correlations between concentrations of amphibole fibres and time between the end of exposure and death. Chrysotile concentrations among workers who died shortly after the end of exposure were higher than among the referents (median difference in concentrations 13 million fibres (f)/g dry weight; p = 0.033, one sided). No quantitative differences in exposure (duration or intensity) could be shown between workers with high and low to intermediate concentrations. Interestingly, all seven workers who had had a high intensity at the end of exposure (> 2.5 f/ml), had low to intermediate chrysotile concentrations at death, whereas those with low exposure were evenly distributed (31 subjects in both concentration categories); hence, there was a dependence between last intensity of exposure and chrysotile concentration (p = 0.014). Among 14 workers with a high average intensity of exposure, both those (n = 5) with high tissue concentrations of chrysotile and those (n = 10) with high tissue concentrations of tremolite fibres had more pronounced fibrosis than those with low to intermediate concentrations (median fibrosis grades for chrysotile: 2 v 1, p = 0.021; for tremolite: 2 v 0.5, p = 0.012). Additionally, workers who died shortly after the end of exposure with high concentrations of chrysotile and crocidolite had smoked more than those with low intermediate concentrations (medians for chrysotile 35 v 15 pack-years, p = 0.030; for crocidolite 37 v 15 pack-years, p = 0.012). The present data indicate that chrysotile has a relatively rapid turnover in human lungs, whereas the amphiboles, tremolite and crocidolite, have a slower turnover. Further, chrysotile retention may be dependent on dose rate. Chrysotile and crocidolite deposition and retention may be increased by tobacco smoking; chrysotile and tremolite by fibrosis.
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| 3. |
- Chiu, D T, et al.
(författare)
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Chemical transformations in individual ultrasmall biomimetic containers
- 1999
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Ingår i: Science. - Stanford Univ, Dept Chem, Stanford, CA 94305 USA. Univ Gothenburg, Dept Chem, S-41296 Gothenburg, Sweden. Pomona Coll, Dept Chem, Claremont, CA 91711 USA. : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 283:5409, s. 1892-1895
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Tidskriftsartikel (refereegranskat)abstract
- Individual phospholipid vesicles, 1 to 5 micrometers in diameter, containing a single reagent or a complete reaction system, were immobilized with an infrared laser optical trap or by adhesion to modified borosilicate glass surfaces. Chemical transformations were initiated either by electroporation or by electrofusion, in each case through application of a short (10-microsecond), intense (20 to 50 kilovolts per centimeter) electric pulse delivered across ultramicroelectrodes. Product formation was monitored by far-field laser fluorescence microscopy. The ultrasmall characteristic of this reaction volume led to rapid diffusional mixing that permits the study of fast chemical kinetics. This technique is also well suited for the study of reaction dynamics of biological molecules within lipid-enclosed nanoenvironments that mimic cell membranes.
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| 5. |
- Forsberg, A., et al.
(författare)
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:6, s. 513-521
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Tidskriftsartikel (refereegranskat)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 6. |
- Kay, E., et al.
(författare)
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NanoSIMS Imaging Reveals the Impact of Ligand-ASO Conjugate Stability on ASO Subcellular Distribution
- 2022
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- The delivery of antisense oligonucleotides (ASOs) to specific cell types via targeted en-docytosis is challenging due to the low cell surface expression of target receptors and inefficient escape of ASOs from the endosomal pathway. Conjugating ASOs to glucagon-like peptide 1 (GLP1) leads to efficient target knockdown, specifically in pancreatic β-cells. It is presumed that ASOs dissociate from GLP1 intracellularly to enable an ASO interaction with its target RNA. It is unknown where or when this happens following GLP1-ASO binding to GLP1R and endocytosis. Here, we use correlative nanoscale secondary ion mass spectroscopy (NanoSIMS) and transmission electron microscopy to explore GLP1-ASO subcellular trafficking in GLP1R overexpressing HEK293 cells. We isotopically label both eGLP1 and ASO, which do not affect the eGLP1-ASO conjugate function. We found that the eGLP1 peptide and ASO are not detected at the same level in the same endosomes, within 30 min of GLP1R-HEK293 cell exposure to eGLP1-ASO. When we utilized different linker chemistry to stabilize the GLP1-ASO conjugate, we observed more ASO located with GLP1 compared to cell incubation with the less stable conjugate. Overall, our work suggests that the ASO separates from GLP1 relatively early in the endocytic pathway, and that linker chemistry might impact the GLP1-ASO function. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 7. |
- Klompstra, Leonie, et al.
(författare)
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Physical activity in daily life in heart failure patients living in two European countries, Volume 17, Issue Supplement S1
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aims: Exercise is recognized as important in patients with heart failure (HF). It is unclear if there are differences in physical activity between European Countries, therefore the aims of this study were to-Assess physical activity levels in HF patients,-Describe the different types of physical activity of HF patients -Explore differences between patients from Spain and Sweden Method: The short International Physical Activity Questionnaire (sIPAQ) was used to assess the level of physical activity during the previous week. The sIPAQ contains seven items to identify the frequency and duration of light, moderate, and vigorous PA, as well as inactivity during the past week. Data was collected during April-July 2014 in Swedish and Spanish HF patients. Differences were analysed using Pearson’s chi-square or Mann-Whitney U test.Results: Population:548 Spanish and 154 Swedish HF patients29% female, mean age 69±12 years, 75% NYHA class II/19% NYHA IIINo differences were found in gender, age NYHA class between the two countries Patients in Sweden compared to Spanish patients:Had a higher mean physical activity levelDid more vigorous activities, like lifting, digging, aerobics, or fast bicyclingDid more moderate activities like carrying light loads, bicycling at a regular pace, or doubles tennis.Did less walking (walking at work and at home, walking to travel from place to place, and any other walking that might be done solely for recreation, sport, exercise, or leisure) Conclusions: Despite that most of the patients were in NYHA class II and not symptomatic even at moderate to high level of activity, one third of them had a low physical activity level in their daily life.We found differences in the kind of physical activities between Spain and Sweden, which could be due to cultural and regional differences. Specific differences and consequences need to be further explored.
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| 8. |
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| 9. |
- Lindvall, O, et al.
(författare)
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Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up
- 1989
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Ingår i: Archives of Neurology. - : American Medical Association (AMA). - 0003-9942. ; 46:6, s. 31-615
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Tidskriftsartikel (refereegranskat)abstract
- By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.
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| 10. |
- Norppa, H., et al.
(författare)
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Chromosomal aberrations and SCEs as biomarkers of cancer risk
- 2006
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 600:1-2, s. 37-45
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
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