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- Jeremy, Kris P., et al.
(författare)
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4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:10, s. 1354-1361
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Tidskriftsartikel (refereegranskat)abstract
- Background Protein 4.1R is an important component of die red cell membrane skeleton. It imparts structural integrity and has transmembrane signaling roles by direct interactions with transmembrane proteins and other membrane skeletal components, notably p55 and calmodulin. Design and Methods Spontaneous and ligation-induced phosphatidylserine exposure on erythrocytes from two patients with 4.1R deficiency were studied, using CD47 glycoprotein and glycophorin C as ligands We also looked for protein abnormalities in the 4.1R - based multiprotein complex. Results Phosphatidylserine exposure was significantly increased in 4.1R-deficient erythrocytes obtained from the two different individuals when ligands to CD47 glycoprotein were bound. Spontaneous phosphatidylserine exposure was normal. 4.1R, glycophorin C and p55 were missing or sharply reduced. Furthermore there was an alteration or deficiency of CD47 glycoprotein and a lack of CD44 glycoprotein. Based on a recent study in 4.1R-deficient mice, we found that there are clear functional differences between interactions of human red cell 4.1R and its murine counterpart Conclusions Glycophorin C is known to bind 4.1R, and we have defined previously that it also binds CD47 From our evidence, we suggest that 4.1R plays a role in the phosphatidylserine exposure signaling pathway that is of Fundamental importance in red cell turnover The linkage of CD44 to 4.1R may be relevant to this process
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- Ferrie, J E, et al.
(författare)
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Diagnosis-specific sickness absence and all-cause mortality in the GAZEL study.
- 2009
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Ingår i: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 63:1, s. 50-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aims to examine diagnosis-specific sickness absence as a risk marker for all-cause mortality. METHODS: Prospective occupational cohort (the GAZEL study). Medically certified sickness absence spells >7 days for 15 diagnostic categories, 1990-1992, were examined in relation to all-cause mortality, January 1993-February 2007. The reference group for each diagnostic category was participants with no spell >7 days for that diagnosis. The participants were French public utility workers (5271 women and 13 964 men) aged 37-51 years in 1990, forming the GAZEL study. Over the follow-up period, there were 144 deaths in women and 758 in men. RESULTS: 7875 employees (41.0%) had at least one spell of sickness absence >7 days over the 3-year period. The commonest diagnoses were mental disorders, musculoskeletal diseases, respiratory diseases and external causes in both sexes; genitourinary diseases in women, and digestive and circulatory diseases in men. Of these common diagnoses, mental disorders in women, hazard ratio (95% confidence intervals) 1.24 (1.1 to 1.4), and mental disorders 1.35 (1.3 to 1.5), digestive diseases 1.29 (1.1 to 1.6) and circulatory diseases 1.35 (1.2 to 1.6) in men were associated with mortality after adjustment for age, employment grade and sickness absence in all other diagnostic categories. CONCLUSIONS: Employees with medically certified absence spells of 1 week or more over a 3-year period had a 60% excess risk of early death. In women and men this excess risk was associated with some of the commonest diagnoses of sickness absence, in particular mental disorders. Sickness absence for mental disorders may be a useful early indicator of groups at increased risk of fatal disease.
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- Head, Jenny, et al.
(författare)
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Diagnosis-specific sickness absence as a predictor of mortality : the Whitehall II prospective cohort study.
- 2008
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1468-5833 .- 0959-8138 .- 1756-1833. ; 337, s. a1469-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether knowing the diagnosis for sickness absence improves prediction of mortality. DESIGN: Prospective cohort study established in 1985-8. Sickness absence records including diagnoses were obtained from computerised registers. SETTING: 20 civil service departments in London. PARTICIPANTS: 6478 civil servants aged 35-55 years. MAIN OUTCOME MEASURES: All cause, cardiovascular, and cancer mortality until 2004, average follow-up 13 years. RESULTS: After adjustment for age, sex, and employment grade, employees who had one or more medically certified spells of sickness absence (>7 days) in a three year period had a mortality 1.7 (95% CI 1.3 to 2.1) times greater than those with no medically certified spells. Inclusion of diagnoses improved the prediction of all cause mortality (P=0.03). The hazard ratio for mortality was 4.7 (2.6 to 8.5) for absences with circulatory disease diagnoses, 2.2 (1.4 to 3.3) for surgical operations, and 1.9 (1.2 to 3.1) for psychiatric diagnoses. Psychiatric absences were also predictive of cancer mortality (2.5 (1.3 to 4.7)). Associations of infectious, respiratory, and injury absences with overall mortality were less marked (hazard ratios from 1.5 to 1.7), and there was no association between musculoskeletal absences and mortality. CONCLUSIONS: Major diagnoses for medically certified absences were associated with increased mortality, with the exception of musculoskeletal disease. Data on sickness absence diagnoses may provide useful information to identify groups with increased health risk and a need for targeted interventions.
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- Kivimäki, Mika, et al.
(författare)
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Diagnosis-specific sick leave as a risk marker for disability pension in a Swedish population.
- 2007
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Ingår i: J Epidemiol Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 61:10, s. 915-20
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diagnosis-specific sick leave as a risk marker for disability pension in a Swedish population.Kivimäki M, Ferrie JE, Hagberg J, Head J, Westerlund H, Vahtera J, Alexanderson K.Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, UK. m.kivimaki@ucl.ac.ukOBJECTIVE: To investigate diagnosis-specific sick leave as a risk marker for subsequent disability pension. DESIGN: A prospective population based cohort study. Exposure to a new medically certified sick leave episode of more than seven days by diagnosis during 1985 was examined in relation to incident cause-specific disability pension through 1996. PARTICIPANTS: The total non-retired population of one Swedish county aged 16 to 49 years, alive and not in receipt of a disability pension at the end of 1985 (176 629 persons; 51% men). MAIN RESULTS: To eliminate confounding by sick leaves that translate into a disability pension, the follow up period for disability pension was started five years after the assessment of sick leave. After adjustment for demographic characteristics, the risk of disability pension from mental disorders was 14.1 times higher (95% confidence interval (CI), 12.1 to 16.4) for those with sick leave for mental disorders than for those with no sick leave. The corresponding hazard ratio for sick leave and disability pension within diagnostic category was 5.7 (95% CI, 5.3 to 6.2) for musculoskeletal diseases and 13.0 (7.7 to 21.8) for gastrointestinal diseases. Irrespective of diagnoses, the hazard ratio for sick leave and disability pension was 3.0 (2.9 to 3.1). CONCLUSIONS: Sick leave may provide an important risk marker for identifying groups at high risk of a disability pension, especially for psychiatric diagnoses.
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- Kivimäki, M, et al.
(författare)
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Sickness absence as a prognostic marker for common chronic conditions : analysis of mortality in the GAZEL study.
- 2008
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Ingår i: Occup Environ Med. - : BMJ. - 1470-7926 .- 1351-0711. ; 65:12, s. 820-6
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Tidskriftsartikel (refereegranskat)abstract
- Sickness absence as a prognostic marker for common chronic conditions: analysis of mortality in the GAZEL study.Kivimäki M, Head J, Ferrie JE, Singh-Manoux A, Westerlund H, Vahtera J, Leclerc A, Melchior M, Chevalier A, Alexanderson K, Zins M, Goldberg M.Department of Epidemiology and Public Health, University College London, London, UK. m.kivimaki@ucl.ac.ukOBJECTIVES: To determine whether sickness absence is a prognostic marker in terms of mortality among people with common chronic conditions. METHODS: Prospective occupational cohort study of 13,077 men and 4871 women aged 37-51 from the National Gas and Electricity Company, France. Records of physician-certified sickness absences over a 3-year period were obtained from employers' registers. Chronic conditions were assessed in annual surveys over the same period. The main outcome measure was all-cause mortality (803 deaths, mean follow-up after assessment of sickness absence: 13.9 years). RESULTS: In Cox proportional hazard models adjusted for age, sex, socioeconomic position and co-morbidity, >28 annual sickness-absence days versus no absence days was associated with an excess mortality risk among those with cancer (hazard ratio 5.4, 95% CI 2.2 to 13.1), depression (1.7, 1.1 to 2.8), chronic bronchitis or asthma (2.7, 1.6 to 4.6) and hypertension (1.6, 1.0 to 2.6). The corresponding hazard ratios for more than five long (>14 days) sickness-absence episodes per 10 person-years versus no such episodes were 5.4 (2.2 to 13.1), 1.8 (1.3 to 2.7), 2.0 (1.3 to 3.2) and 1.8 (1.2 to 2.7), respectively. Areas under receiver operating characteristics curves for these absence measures varied between 0.56 and 0.73, indicating the potential of these measures to distinguish groups at high risk of mortality. The findings were consistent across sex, age and socioeconomic groups and in those with and without co-morbid conditions. CONCLUSION: Data on sickness absence may provide useful prognostic information for common chronic conditions at the population level.
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- Kristjánsdóttir, Helga, 1966-
(författare)
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The PD-1 pathway and the complement system in systemic lupus erythematosus
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autoimmune diseases occur in up to 3-5% of the general population and represent a diverse collection of diseases with regards to clinical manifestations. The unifying factor of autoimmune diseases is tissue and organ damage as a result of an immune response mounted against self-antigens. Systemic lupus erythematosus (SLE) is considered a prototype of human systemic autoimmune diseases. The etiology of SLE is as yet largely unknown, but both epidemiological and genetic data suggest an interplay between numerous and varying genetic and environmental factors. There is compelling evidence for a strong genetic component in SLE. The disease has a high λsibs value and familial clustering is apparent. Multiple susceptibility loci have been identified, some of which are syntenic between humans and mice and some of which overlap with other autoimmune diseases. This thesis is based on analysis of Icelandic multicase SLE families and Swedish SLE patients. Paper I is a study of the association of C4A protein deficiency (C4AQ0) with SLE in the multicase families and shows a significantly increased frequency of C4AQ0 in the families. The genetic basis for C4AQ0 varies and C4AQ0 is found on different MHC haplotypes, pointing to C4AQ0 as an independent risk factor for SLE. Paper II describes the association of low MBL serum levels with SLE in the families and identifies low MBL as risk factor for SLE in families that carry the defect. Low MBL was furthermore found to mediate an additive risk when found in combination with C4AQ0. In paper III cellular expression the PD-1 co-inhibitory receptor on T cells was studied. A polymorphism in the PDCD1 gene, PD-1.3A was previously associated with SLE in the multicase families. The polymorphism is thought to disrupt expression of the gene and may lead to decreased expression of the PD-1 receptor. The study demonstrates lower PD-1 expression in SLE patients and relatives in correlation to the PD-1.3A genotype. Paper IV is a compiled analysis of the SLE families, including PD-1.3A, C4AQ0, low MBL, autoimmune diseases and autoantibody profiles. The study demonstrates clustering of different autoimmune diseases and autoantibodies in families that are heterogenic with regards to the genetic susceptibility factors, PD-1.3A, C4AQ0 and low MBL.
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- Melchior, Maria, et al.
(författare)
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Using sickness absence records to predict future depression in a working population : prospective findings from the GAZEL cohort.
- 2009
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Ingår i: American journal of public health. - 1541-0048. ; 99:8, s. 1417-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We tested the hypothesis that sickness absence from work predicts workers' risk of later depression. METHODS: Study participants (n = 7391) belonged to the French GAZEL cohort of employees of the national gas and electricity company. Sickness absence data (1996-1999) were obtained from company records. Participants' depression in 1996 and 1999 was assessed with the Center for Epidemiologic Studies-Depression (CES-D) scale. The analyses were controlled for baseline age, gender, marital status, occupational grade, tobacco smoking status, alcohol consumption, subthreshold depressive symptoms, and work stress. RESULTS: Among workers who were free of depression in 1996, 13% had depression in 1999. Compared with workers with no sickness absence during the study period, those with sickness absence were more likely to be depressed at follow-up (for 1 period of sickness absence, fully adjusted odds ratio [OR] = 1.53, 95% confidence interval [CI] = 1.28, 1.82; for 2 or more periods, fully adjusted OR = 1.95, 95% CI = 1.61, 2.36). Future depression was predicted both by psychiatric and nonpsychiatric sickness absence (fully adjusted OR = 3.79 [95% CI = 2.81, 5.10] and 1.41 [95% CI = 1.21, 1.65], respectively). CONCLUSIONS: Sickness absence records may help identify workers vulnerable to future depression.
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- Westerlund, Hugo, et al.
(författare)
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Does working while ill trigger serious coronary events? The Whitehall II study.
- 2009
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Ingår i: Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine. - 1536-5948. ; 51:9, s. 1099-104
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Working while ill has been found to predict coronary heart disease. We tested if this association was due to triggering. METHODS: We used a nested case-control study in an occupational cohort to examine sickness absences during a 2-year period immediately before the first coronary event for 133 cases and 928 matched controls without a history of coronary events. Working while ill was defined as no absence despite being unhealthy (suboptimal self-rated health or psychological distress). RESULTS: The odds of a coronary event were not higher for cases who worked while ill than for correspondingly unhealthy controls who took >0 to 14 days of absence per year (OR = 0.62; 95% CI = 0.28 to 1.38). These results were little affected by multiple adjustments. CONCLUSIONS: We found no evidence that working while ill acts as a short-term trigger for coronary events.
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