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| 3. |
- Gallo, Valentina, et al.
(författare)
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Smoking and risk for amyotrophic lateral sclerosis : analysis of the EPIC cohort
- 2009
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Ingår i: Annals of Neurology. - New York : J. Wiley & Sons. - 0364-5134 .- 1531-8249. ; 65:4, s. 378-385
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
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| 4. |
- Neyens, G., et al.
(författare)
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g-Factor Measurements on Relativistic Isomeric Beams Produced by Fragmentation and U-fission: The g-RISING Project at GSI
- 2007
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 38:4, s. 1237-1247
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Tidskriftsartikel (refereegranskat)abstract
- Within the RISING (Rare ISotope INvestigations @ GSI) Collaboration at GSI, g factor measurements have been performed on isomeric states in neutron-rich isotopes approaching Sn-132 and in the neutron deficient Pb-region (the g-RISING campaign). We present the experimental technique and some typical aspects related to such studies on relativistic beams selected with the FRS fragment separator. First results are presented for the (19/2(+)) 4.5 mu s isomeric state in Sn-127, which has been produced by means of fission of a relativistic U-238 beam on the one hand, and by the fragmentation of a relativistic Xe-136 beam on the other hand. Spin-alignment has been observed in both reactions. It was the first time that spin-alignment has been established in a relativistic fission reaction.
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| 5. |
- Bergink, S, et al.
(författare)
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DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A
- 2006
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 20:10, s. 1343-1352
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin changes within the context of DNA repair remain largely obscure. Here we show that DNA damage induces monoubiquitylation of histone H2A in the vicinity of DNA lesions. Ultraviolet (UV)-induced monoubiquitylation of H2A is dependent on functional nucleotide excision repair and occurs after incision of the damaged strand. The ubiquitin ligase Ring2 is required for the DNA damage-induced H2A ubiquitylation. UV-induced ubiquitylation of H2A is dependent on the DNA damage signaling kinase ATR (ATM- and Rad3-related) but not the related kinase ATM (ataxia telangiectasia-mutated). Although the response coincides with phosphorylation of variant histone H2AX, H2AX was not required for H2A ubiquitylation. Together our data show that monoubiquitylation of H2A forms part of the cellular response to UV damage and suggest a role of this modification in DNA repair-induced chromatin remodeling.
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- de Vocht, F, et al.
(författare)
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Exposure to inhalable dust and its cyclohexane soluble fraction since the 1970s in the rubber manufacturing industry in the European Union
- 2008
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 65:6, s. 384-391
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: As exposures to airborne particulates in the European rubber industry might still be causing genotoxic risks, it is important to assess trends in levels of inhalable dust and its cyclohexane soluble fraction (CSF) between the 1970s and 2003. Methods: 13 380 inhalable and 816 respirable dust and 5657 CSF measurements, collected within the framework of the European Union Concerted Action EXASRUB, were analysed. Hierarchical mixed effects models were applied to assess exposure trends, taking into account between-factory, between-worker/location and day-to-day variances. Results: Geometric mean levels of inhalable dust and CSF exposure changed by 24% (range -5.8 to +2.9%) and -3% (range -8.6 to 0%) per year, respectively. Significant reductions in inhalable dust concentrations were found in all countries for handling of crude materials and mixing and milling (-7% to -4% per year), as well as for miscellaneous workers (-11% to -5% per year), while significant CSF exposure reductions were found in curing (-8.6% per year) and maintenance and engineering departments (-5.4% per year). Conclusion: These analyses suggest that on average exposure levels of inhalable dust and its CSF in the European rubber manufacturing industry have steadily declined. Most likely genotoxic risks have also lessened over time since exposure levels have decreased and the most toxic chemicals have been replaced. In addition to differences in exposure reductions and levels among various stages of the production process, large differences across countries were noted. These patterns should be taken into account in retrospective assessment of exposure for epidemiological studies assessing cancer risk in the rubber industry.
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| 7. |
- Dieperink, Willem, et al.
(författare)
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Boussignac continuous positive airway pressure for the management of acute cardiogenic pulmonary edema : prospective study with a retrospective control group.
- 2007
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 7, s. 40-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Continuous positive airway pressure (CPAP) treatment for acute cardiogenic pulmonary edema can have important benefits in acute cardiac care. However, coronary care units are usually not equipped and their personnel not adequately trained for applying CPAP with mechanical ventilators. Therefore we investigated in the coronary care unit setting the feasibility and outcome of the simple Boussignac mask-CPAP (BCPAP) system that does not need a mechanical ventilator. METHODS: BCPAP was introduced in a coronary care unit where staff had no CPAP experience. All consecutive patients transported to our hospital with acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a peripheral arterial oxygen saturation of < 95% while receiving oxygen, were included in a prospective BCPAP group that was compared with a historical control group that received conventional treatment with oxygen alone. RESULTS: During the 2-year prospective BCPAP study period 108 patients were admitted with acute cardiogenic pulmonary edema. Eighty-four of these patients (78%) were treated at the coronary care unit of which 66 (61%) were treated with BCPAP. During the control period 66 patients were admitted over a 1-year period of whom 31 (47%) needed respiratory support in the intensive care unit. BCPAP treatment was associated with a reduced hospital length of stay and fewer transfers to the intensive care unit for intubation and mechanical ventilation. Overall estimated savings of approximately euro 3,800 per patient were achieved with the BCPAP strategy compared to conventional treatment. CONCLUSION: At the coronary care unit, BCPAP was feasible, medically effective, and cost-effective in the treatment of acute cardiogenic pulmonary edema. Endpoints included mortality, coronary care unit and hospital length of stay, need of ventilatory support, and cost (savings).
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| 8. |
- Lozeva, R. L., et al.
(författare)
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New sub-us Isomers in 125Sn, 127Sn, 129Sn and Isomer Systematics of 124-130Sn
- 2008
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 77:6
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Tidskriftsartikel (refereegranskat)abstract
- New sub-mu s isomers have been observed in the neutron-rich Sn isotopes. Sn-125,Sn-127,Sn-129 nuclei have been produced in a relativistic fission reaction of U-238 on a Be-9 target at 750 A.MeV and by the fragmentation of Xe-136 at 600 A.MeV populating high-spin yrast states. In addition to the already known mu s isomers, three new ones with sub-mu s half-lives have been observed. These yrast isomers are the high-spin members of the nu(d(3/2)(-1)h(11/2)(-2)) and nu h(11/2)(-n), seniority v = 3 multiplets leading to isomeric (23/2(+)) and (27/2(-)) states, respectively. Added to the already known 19/2(+)mu s isomers in this region the current work completes the systematic information of neutron-hole excitations toward the filling of the last h(11/2) orbital at N = 82. The results are discussed in the framework of state-of-the-art shell-model calculations using realistic interactions.
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| 9. |
- Luijsterburg, MS, et al.
(författare)
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Heterochromatin protein 1 is recruited to various types of DNA damage
- 2009
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 185:4, s. 577-586
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Tidskriftsartikel (refereegranskat)abstract
- Heterochromatin protein 1 (HP1) family members are chromatin-associated proteins involved in transcription, replication, and chromatin organization. We show that HP1 isoforms HP1-α, HP1-β, and HP1-γ are recruited to ultraviolet (UV)-induced DNA damage and double-strand breaks (DSBs) in human cells. This response to DNA damage requires the chromo shadow domain of HP1 and is independent of H3K9 trimethylation and proteins that detect UV damage and DSBs. Loss of HP1 results in high sensitivity to UV light and ionizing radiation in the nematode Caenorhabditis elegans, indicating that HP1 proteins are essential components of DNA damage response (DDR) systems. Analysis of single and double HP1 mutants in nematodes suggests that HP1 homologues have both unique and overlapping functions in the DDR. Our results show that HP1 proteins are important for DNA repair and may function to reorganize chromatin in response to damage.
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| 10. |
- Marteijn, JA, et al.
(författare)
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Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response
- 2009
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 186:6, s. 835-847
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin modifications are an important component of the of DNA damage response (DDR) network that safeguard genomic integrity. Recently, we demonstrated nucleotide excision repair (NER)–dependent histone H2A ubiquitination at sites of ultraviolet (UV)-induced DNA damage. In this study, we show a sustained H2A ubiquitination at damaged DNA, which requires dynamic ubiquitination by Ubc13 and RNF8. Depletion of these enzymes causes UV hypersensitivity without affecting NER, which is indicative of a function for Ubc13 and RNF8 in the downstream UV–DDR. RNF8 is targeted to damaged DNA through an interaction with the double-strand break (DSB)–DDR scaffold protein MDC1, establishing a novel function for MDC1. RNF8 is recruited to sites of UV damage in a cell cycle–independent fashion that requires NER-generated, single-stranded repair intermediates and ataxia telangiectasia–mutated and Rad3-related protein. Our results reveal a conserved pathway of DNA damage–induced H2A ubiquitination for both DSBs and UV lesions, including the recruitment of 53BP1 and Brca1. Although both lesions are processed by independent repair pathways and trigger signaling responses by distinct kinases, they eventually generate the same epigenetic mark, possibly functioning in DNA damage signal amplification.
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| 11. |
- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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| 13. |
- Vermeulen, R P, et al.
(författare)
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Prehospital diagnosis in STEMI patients treated by primary PCI : the key to rapid reperfusion.
- 2008
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Ingår i: Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. - 1568-5888. ; 16:1, s. 5-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary coronary intervention (PCI) for acute myocardial infarction should be performed as quickly as possible, with a door-toballoon time of less then 90 minutes. However, in daily practice this cannot always be achieved. Prehospital diagnosis of ST-elevation myocardial infarction (STEMI) is of major importance in reducing time to treatment, in particular when patients can be transported directly to a centre with interventional capacities. OBJECTIVES: The aim of the current study was to evaluate the time from prehospital diagnosis of STEMI to balloon inflation and identify factors related to treatment delay in patients directly referred to the catheterisation laboratory of the University Medical Centre of Groningen. METHODS: A cross-sectional descriptive design was used to collect data on patients treated with primary PCI after prehospital diagnosis of STEMI. RESULTS: Median prehospital diagnosis-to-balloon time was 64 minutes for patients directly admitted to the catheterisation laboratory and 75 minutes for patients initially admitted to the coronary care unit. A delay longer than 90 minutes was observed in 18 patients. Higher age was associated with longer delay times (p=0.041). Long delays were not associated with diabetes (p=0.293), time from symptom onset to prehospital diagnosis (p=0.87) or time of day (p=0.09). Initial unavailability of the catheterisation laboratory due to running procedures contributed to longer delay times in ten cases. CONCLUSION: Prehospital diagnosis of STEMI and direct referral to a catheterisation laboratory for primary PCI allows a prehospital diagnosis-toballoon time of less than 90 minutes in 82% of patients. Older patients are at risk of longer delays. (Neth Heart J 2008;16:5-9.).
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