| 1. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
- 2014
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
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| 2. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Serum estradiol associates with blood hemoglobin in elderly men; The MrOS Sweden Study
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:7, s. 2549-56
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Tidskriftsartikel (refereegranskat)abstract
- Context: Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing testosterone has been regarded as part of normal ageing. However, the association between Hb and serum estradiol is incompletely known. Objective: To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer. Design, Setting and Participants: The MrOS (Osteoporotic Fractures in Men) is a population-based study (n=918, median age 75.3 years, range 70-81 years). Main Outcome Measures: We evaluated total estradiol in relation to Hb and adjusted for potential confounders (i.e. age, body mass index (BMI), erythropoietin (EPO), total testosterone, cystatin C, iron- and B-vitamin status). Results: Estradiol correlated negatively with age (r=-0.14, p<0.001). Hb correlated (age adjusted) positively with estradiol (r=0.21, p<0.001) and testosterone (r=0.10, p<0.01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C and free T4 but not testosterone. After exclusion of subjects with Hb <130g/L and/or testosterone <8 nmol/L (n=99), the correlation between Hb and testosterone was no longer significant, whereas the associations between Hb and estradiol remained. After adjusting for age, BMI and EPO, men with lower estradiol levels were more likely to have Hb in the lowest quartile of values [OR per SD decrease in estradiol = 1.61 (95% CI 1.34-1.93)]. Anemic subjects (Hb <130 g/L) had lower mean estradiol than non-anemic (67.4 vs 79.4 pmol/L, p<0.001). Conclusions: Estradiol correlated, positively and independently, with Hb. Decreased estradiol might partly explain the age-related Hb decline observed in healthy elderly men.
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| 3. |
- Bergman, Birgitta, 1941, et al.
(författare)
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Ocular changes, risk markers for eye disorders and effects of cataract surgery in elderly people: a study of an urban Swedish population followed from 70-97 years of age
- 2004
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 82, s. 166-74
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the prevalence of and potential risk factors for ocular disorders and the effects of timing of cataract surgery from age 70–97 years. Population: A representative population sample taken from within the Gerontological and Geriatric Population Studies (H 70) in Gothenburg, Sweden (n = 958). All subjects underwent eye examinations at age 70 years in 1971 and subsequently at ages 82, 88, 95 and 97 years. All inhabitants of Gothenburg aged 95 and 97 years were invited to participate in the study. Results: Decreased vision (visual acuity ≤ 0.5) was found in 20% and 80% of subjects at ages 82 and 97 years, respectively. Blood folate and physical activity at age 70 years correlated positively and body mass index (BMI) negatively to visual acuity (VA) ≥ 0.8 at ages 82 and 88 years. Smoking at age 70 years correlated to early age-related maculopathy (ARM). Cataract surgery had been performed in 40% of subjects at age 97 years. Surgery 2 years earlier led to a 15% increase in time spent with improved vision. Conclusions: The deterioration of vision in elderly people is a major health problem, for which ‘low’ folate status, smoking, ‘high’ BMI and low physical activity are potential risk factors. Early cataract surgery is also beneficial in very old patients.
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| 4. |
- Bram Ednersson, Susanne, et al.
(författare)
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Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients
- 2018
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 181:6, s. 770-781
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1year from diagnosis (REF/REL), and 53 who were progression-free more than 5years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P=76x10(-10)). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P=14x10(-9)). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.
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| 5. |
- Bram Ednersson, Susanne, et al.
(författare)
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Proteomic analysis in diffuse large B-cell lymphoma identifies dysregulated tumor microenvironment proteins in non-GCB/ABC subtype patients
- 2021
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 62:10, s. 2360-2373
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Tidskriftsartikel (refereegranskat)abstract
- The complexity of the activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL) subtype is probably not only explained by genetic alterations and methods to measure global protein expression could bring new knowledge regarding the pathophysiology. We used quantitative proteomics to analyze the global protein expression of formalin-fixed paraffin-embedded (FFPE) tumor tissues from 202 DLBCL patients. We identified 6430 proteins and 498 were significantly regulated between the germinal center B-cell like (GCB) and non-GCB groups. A number of proteins previously not described to be upregulated in non-GCB or ABC DLBCL was found, e.g. CD64, CD85A, guanylate-binding protein 1 (GBP1), interferon-induced proteins with tetratricopeptide repeat (IFIT)2, and mixed lineage kinase domain-like protein (MLKL) and immunohistochemical staining showed higher expression of GBP1 and MLKL. A cluster analysis revealed that the most prominent cluster contained proteins involved in the tumor microenvironment and regulation of the immune system. Our data suggest that the therapeutic focus should be expanded toward the tumor microenvironment in non-GCB/ABC subtype patients.
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| 6. |
- Bram Ednersson, Susanne, et al.
(författare)
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TBLR1 and CREBBP as potential novel prognostic immunohistochemical biomarkers in diffuse large B-cell lymphoma
- 2020
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:11, s. 2595-2604
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have identified prognostic mutational clusters for diffuse large B-cell lymphoma (DLBCL) patients, both within and outside the original cell-of-origin (COO) classification. For many of these mutations, there is limited information regarding the corresponding protein expression. With the aim to determine the relationship of protein expression and intensity to COO and prognosis, we used digital image analysis to quantitate immunohistochemical staining of CREBBP, IRF8, EZH2, and TBLR1 in 209 DLBCL patients. We found that patients with strong nuclear expression of TBLR1 had inferior progression-free survival (PFS) and overall survival (OS) in univariable analysis and inferior PFS in multivariable analysis. Patients with higher proportion of intermediate to strong nuclear CREBBP expression had a worse PFS and OS in univariable analysis. CREBBP was expressed with stronger intensity in non-GCB patients and the prognostic impact was restricted to this subgroup. These findings suggest that high nuclear protein expression of TBLR1 and CREBBP is negatively associated with prognosis in DLBCL.
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| 7. |
- Ekberg, Sara, et al.
(författare)
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Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century - a Swedish lymphoma register study
- 2020
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:6, s. 1083-1092
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000-2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors.
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| 8. |
- Hagberg, Hans, et al.
(författare)
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Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry Study
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:3, s. 668-676
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Tidskriftsartikel (refereegranskat)abstract
- Treatment for follicular lymphoma (FL) improved with rituximab. In Sweden, first-line rituximab was gradually introduced between 2003 and 2007, with regional differences. The first national guidelines for FL were published in November 2007, recommending rituximab in first-line therapy. Using the population-based Swedish Lymphoma Registry, 2641 patients diagnosed with FL from 2000 to 2010 were identified and characterized by year and region of diagnosis, age (median, 65 years), gender (50% men), first-line therapy and clinical risk factors. Overall and relative survivals were estimated by calendar periods (2000-2002, 2003-2007 and 2008-2010) and region of diagnosis. With each period, first-line rituximab use and survival increased. Survival was superior in regions where rituximab was quickly adopted and inferior where slowly adopted. These differences were independent in multivariable analyses. Ten-year relative survival for patients diagnosed 2003-2010 was 92%, 83%, 78% and 64% in the age groups 18-49, 50-59, 60-69 and ≥70, respectively. With increasing rituximab use, male sex emerged as an adverse factor. Survival improved in all patient categories, particularly in elderly women. The introduction and the establishment of rituximab have led to a nationwide improvement in FL survival. However, rituximab might be inadequately dosed in younger women and men of all ages. © 2015 Macmillan Publishers Limited. All rights reserved.
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| 9. |
- Junevik, Katarina, 1965, et al.
(författare)
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The expression of NK cell inhibitory receptors on cytotoxic T cells in B-cell chronic lymphocytic leukaemia (B-CLL).
- 2007
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Ingår i: Annals of hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 86:2, s. 89-94
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Tidskriftsartikel (refereegranskat)abstract
- Immune surveillance of tumours is mediated by cytotoxic T cells (CTL) that recognise tumour antigen. Reduced reactivity of CTL towards tumour cells could thus lead to disease progression and loss of tumour control. In B-cell chronic lymphocytic leukaemia (B-CLL), the function of tumour-reactive CTL seems to correlate inversely to disease stage. Inhibitory NK cell receptors are known to suppress the CTL response upon interaction with major histocompatibility complex (MHC) class I and increased expression of such receptors on CTL may inhibit the anti-tumour response. So, the aim of this study was to investigate the expression of NK cell inhibitory receptors on CTL in B-CLL patients and if such expression correlated to disease stage. CD8+ T cells from B-CLL patients in Binet stage A (n = 26) and stage C (n = 14) and healthy controls (n = 14) were analysed for the expression of killer immunoglobulin-like receptors (KIR) CD158a (KIR2DL1), CD158b (KIR2DL2), CD158e (KIR3DL1) and the C-type lectin receptor CD94, by flow cytometry analysis. Patients with advanced disease (Binet stage C) had a significantly greater percentage of CTL expressing CD158b, CD158e and CD94 than patients with non-progressive disease (Binet stage A) and healthy controls. Stage C patients also had a significantly higher percentage of CTL expressing CD158a than stage A patients. No statistically significant differences were found between Binet A patients and healthy controls. Our results suggest that increased expression of KIR and CD94 on CTL in advanced stage B-CLL may potentially contribute to the impaired anti-tumour immune response in these patients.
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| 10. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly
- 2007
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Ingår i: J Intern Med. - 0954-6820. ; 261:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. DESIGN AND SETTING: Population-based study of 209 community-dwelling subjects, mean age 76 years. INTERVENTIONS: Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. MAIN OUTCOME MEASURES: Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. RESULTS: Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). CONCLUSIONS: The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.
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