| 1. |
- Axelsson, Eva, et al.
(författare)
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Recessiveness and Dominance in Barley Mutants Deficient in Mg-Chelatase Subunit D, an AAA Protein Involved in Chlorophyll Biosynthesis.
- 2006
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Ingår i: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 18:12, s. 3606-3616
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Tidskriftsartikel (refereegranskat)abstract
- Mg-chelatase catalyzes the insertion of Mg2+ into protoporphyrin IX at the first committed step of the chlorophyll biosynthetic pathway. It consists of three subunits: I, D, and H. The I subunit belongs to the AAA protein superfamily ( ATPases associated with various cellular activities) that is known to form hexameric ring structures in an ATP-dependant fashion. Dominant mutations in the I subunit revealed that it functions in a cooperative manner. We demonstrated that the D subunit forms ATP-independent oligomeric structures and should also be classified as an AAA protein. Furthermore, we addressed the question of cooperativity of the D subunit with barley (Hordeum vulgare) mutant analyses. The recessive behavior in vivo was explained by the absence of mutant proteins in the barley cell. Analogous mutations in Rhodobacter capsulatus and the resulting D proteins were studied in vitro. Mixtures of wild-type and mutant R. capsulatus D subunits showed a lower activity compared with wild-type subunits alone. Thus, the mutant D subunits displayed dominant behavior in vitro, revealing cooperativity between the D subunits in the oligomeric state. We propose a model where the D oligomer forms a platform for the stepwise assembly of the I subunits. The cooperative behavior suggests that the D oligomer takes an active part in the conformational dynamics between the subunits of the enzyme.
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| 2. |
- Bayani, Jane, et al.
(författare)
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Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- 2021
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
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| 3. |
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| 4. |
- Hedman, Erik, et al.
(författare)
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Proteomic identification of glucocorticoid receptor interacting proteins
- 2006
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 6:10, s. 3114-26
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Tidskriftsartikel (refereegranskat)abstract
- The glucocorticoid receptor (GR) acts as a ligand dependent transcription factor but can also cross talk with other signaling pathways via protein-protein interactions. In this paper we describe methods to study novel cytosolic GR interacting proteins, using mAb based immunoaffinity chromatography of GR from rat liver cytosol. Co-purifying proteins were identified by 2-DE in combination with MALDI-TOF-MS. Non-liganded/non-activated and in vitro liganded/activated GR, respectively, co-purifies with specific sets of proteins. Of these 34 were conclusively identified, seven have previously been reported to be part of the GR-complex, revealing 27 new possible interacting candidates for the GR-complex. Of the novel GR interacting proteins the major vault protein, TATA binding interacting protein 49a and glycoprotein PP63 were of special interest. Furthermore, using 2-D DIGE we show that the set of proteins interacting with non-liganded GR is distinctly different in protein amount compared to the proteins found with liganded/activated GR. This suggests the presence of different GR complexes in the cell, which was further substantiated by the finding of several separate GR native protein complexes, "GR-receptosomes", using blue native gel electrophoresis. Our findings suggest the existence of several new mechanisms for GR signaling and regulation.
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| 5. |
- Janssen, Julie M, et al.
(författare)
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Population Pharmacokinetics of Docetaxel, Paclitaxel, Doxorubicin and Epirubicin in Pregnant Women with Cancer : A Study from the International Network of Cancer, Infertility and Pregnancy (INCIP).
- 2021
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 60:6, s. 775-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy.OBJECTIVE: With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women.METHODS: PK data from 9, 20, 22 and 16 pregnant cancer patients from the International Network of Cancer, Infertility and Pregnancy (INCIP) were available for docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. These samples were combined with available PK data from non-pregnant patients. Empirical non-linear mixed-effects models were developed, evaluating fixed pregnancy effects and gestational age as covariates.RESULTS: Overall, 82, 189, 271, and 227 plasma samples were collected from pregnant patients treated with docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. The plasma PK data were adequately described by the respective models for all cytotoxic drugs. Typical increases in central and peripheral volumes of distribution of pregnant women were identified for docetaxel, paclitaxel, doxorubicin and epirubicin. Additionally, docetaxel, doxorubicin and paclitaxel clearance were increased in pregnant patients, resulting in lower exposure in pregnant women compared with non-pregnant patients.CONCLUSION: Given the interpatient variability, the identified pregnancy-induced changes in PK do not directly warrant dose adjustments for the studied drugs. Nevertheless, these results underscore the need to investigate the efficacy of chemotherapy, when administered during pregnancy.
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| 6. |
- Lundqvist, Lars-Olov, 1958-, et al.
(författare)
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Influence of mental health service provision on the perceived quality of life among psychiatric outpatients : associations and mediating factors
- 2024
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the relationship between perceived mental health service provision and quality of life (QoL) as perceived by patients in psychiatric outpatient care.Methods A total of 373 adult patients registered at 15 psychiatric outpatient clinics in three regions in central and southern Sweden were included in the study. Survey data were collected using a questionnaire on mental health service provision, symptom severity, recovery, clinical diagnosis, sociodemographics (serving as independent variables) and QoL (serving as the dependent variable). Three aspects of mental health service provision were used: patients' perceived quality of care, perceived staff-patient interaction, and patient reported psychiatric treatments. Structural equation modelling was used to model the relationship among the variables.Results Variables in mental health service provision showed few direct associations with patients' perceived QoL. Instead, the associations of mental health service provision on QoL were mainly mediated through symptom severity and recovery. These relationships were retained after adjusting for sociodemographic variables and clinical diagnoses. The final model achieved excellent goodness of fit (chi 2 = 49.502, p = 0.230, RMSEA = 0.020, CFI = 0.997 and a SRMR = 0.024).Conclusion This study shows that mental health service provision is associated with patients' perceived QoL; however, this association is mostly indirect and mediated by reduced symptom severity and increased recovery. This finding can help inform the design of future interventions to enhance service provision to improve patients' QoL.
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| 7. |
- Marusarz, Marika, et al.
(författare)
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Good nursing care for older nursing home clients in a Nordic context.
- 2009
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Ingår i: Verksamhetsförlagd utbildning i en föränderlig vård - en kvalitetsutmaning. - Borås. ; :4
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Konferensbidrag (refereegranskat)abstract
- Introduction: In order to make nursing homes more attractive as work places in the Nordic countries, it should be important to identify possible issues that are central in good nursing care in this context. Aim: The aim of this study was to illuminate and interpret how good nursing care for older nursing home clients may be narrated by registered nurses in a Nordic context. Methods: Nine expert nurses from nursing homes in Denmark, Finland, Norway and Sweden narrated experiences of good nursing care for older people that were tape recorded, transcribed verbatim and analysed by means of qualitative content analysis. Results: Communication, creativity and community were the themes that constituted good nursing care for older people in the studied context. It was interpreted as a process of reciprocity between caregivers, clients and significant others, characterised by transcendence for the individuals that took part in the process. Discussion/Conclusion: Good nursing care in nursing homes demands mature individuals who are conscious and skilled professionals able to create reciprocity in the care context. Such professional nurses could also serve as radiant role models to other registered nurses who are hesitant in entering nursing care of older people.
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| 8. |
- Norsker, Filippa Nyboe, et al.
(författare)
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Neurologic disorders in long-term survivors of neuroblastoma–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program
- 2020
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Ingår i: Acta Oncologica. - 0284-186X. ; 59:2, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma. Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959–2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors. Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7–3.6) and an AER of 16 per 1,000 person-years (95% CI 12–19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma. Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.
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| 9. |
- Norsker, Filippa Nyboe, et al.
(författare)
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Somatic late effects in 5-year survivors of neuroblastoma : a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia study
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 143:12, s. 3083-3096
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Tidskriftsartikel (refereegranskat)abstract
- Because of the rarity of neuroblastoma and poor survival until the 1990s, information on late effects in neuroblastoma survivors is sparse. We comprehensively reviewed the long-term risk for somatic disease in neuroblastoma survivors. We identified 721 5-year survivors of neuroblastoma in Nordic population-based cancer registries and identified late effects in national hospital registries covering the period 1977–2012. Detailed treatment information was available for 46% of the survivors. The disease-specific rates of hospitalization of survivors and of 152,231 randomly selected population comparisons were used to calculate standardized hospitalization rate ratios (SHRRs) and absolute excess risks (AERs). During 5,500 person-years of follow-up, 501 5-year survivors had a first hospital contact yielding a SHRR of 2.3 (95% CI 2.1–2.6) and a corresponding AER of 52 (95% CI 44–60) per 1,000 person-years. The highest relative risks were for diseases of blood and blood-forming organs (SHRR 3.8; 95% CI 2.7–5.4), endocrine diseases (3.6 [3.1–4.2]), circulatory system diseases (3.1 [2.5–3.8]), and diseases of the nervous system (3.0 [2.6–3.3]). Approximately 60% of the excess new hospitalizations of survivors were for diseases of the nervous system, urinary system, endocrine system, and bone and soft tissue. The relative risks and AERs were highest for the survivors most intensively treated. Survivors of neuroblastoma have a highly increased long-term risk for somatic late effects in all the main disease groups as compared to background levels. Our results are useful for counseling survivors and should contribute to improving health care planning in post-therapy clinics.
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| 10. |
- Schröder, Ingrid, et al.
(författare)
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Glutamyl-tRNA reductase activity in Bacillus subtilis is dependent on the hemA gene product
- 1992
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Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; , s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- The Bacillus subtilis hemAXCDBL operon encodes enzymes for the synthesis of 5-aminolaevulinic acid via the C5 pathway (hemA and hemL) and uroporphyrinogen III (hemB, hemC and hemD). B. subtilis HemA protein (molecular mass 50 kDa) was overexpressed in hemA mutants of both Escherichia coli and B. subtilis. A mutant B. subtilis HemA protein with a Cys to Tyr change at position 105 was also overexpressed. Both wild-type and mutant HemA proteins migrated as oligomers (molecular mass greater-than-or-equal-to 230 kDa) on gel-filtration columns. All column fractions containing wild-type HemA protein had glutamyl-tRNA reductase activity. No glutamyl-tRNA reductase activity was found with the mutant HemA protein. It is concluded that the B. subtilis hemA gene product is identical to, or part of, the glutamyl-tRNA reductase of the C5 pathway.
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