| 1. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia
- 2011
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 96:8, s. 1161-1169
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Tidskriftsartikel (refereegranskat)abstract
- Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
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| 2. |
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| 3. |
- Sassi, Atfa, et al.
(författare)
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Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels
- 2014
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 133:5, s. 1410-U681
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. Objective: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. Methods: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. Results: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p. Glu340del and p. Leu83Ser). A third homozygous mutation (p. Asp502Tyr) and the p. Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. Conclusion: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.
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| 4. |
- Berg, Marie, 1955, et al.
(författare)
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Breastfeeding and its impact on daily life in women with type 1 diabetes during the first six months after childbirth: a prospective cohort study
- 2012
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Ingår i: International Breastfeeding Journal. - London : Springer Science and Business Media LLC. - 1746-4358. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: For mothers with diabetes, breastfeeding is a great challenge due to their struggle with potentially unstable blood glucose levels. This paper explores breastfeeding attitudes and impact of breastfeeding on the daily life of mothers with type 1 diabetes compared with non-diabetic mothers. Methods: We performed a prospective cohort study of 108 mothers with type 1 diabetes and a reference group of 104 mothers in the west of Sweden. Data were collected through medical records and structured telephone interviews at 2 and 6 months after childbirth. Results: Women in both the diabetes group and the reference group had high levels of confidence (84% and 93% respectively) in their breastfeeding capacity before childbirth, and 90% assessed breastfeeding as a positive and an important experience during the six months of follow-up. About 80% assessed breastfeeding as influencing daily life ‘very much’ or ‘quite a lot’ at 2 months as did 60% at 6 months, with no difference between the groups. Inmothers with diabetes, the impact of breastfeeding on the priority of other duties decreased over time, as did feelings of time pressure and negative effects on patterns of sleep. Compared to the reference group, mothers with diabetes at 6 months remained more affected by disruptions in daily life and they felt more worried about their health both at 2 and 6 months after childbirth. For the reference group mothers’ sensitivity to unexpected disruptions in daily routines decreased between 2 and 6 months after childbirth, and they expressed a greater need to organize their time than mothers with diabetes. Conclusion: Mothers with diabetes type 1 express more worry for own health and are more sensitive to distruptions. To balance their everyday life and to reduce the risk of stress and illhealth they are therefor, compared to other mothers, likely to need additional professional and peer support.
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| 5. |
- Berglund, Karin, 1967-, et al.
(författare)
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Engaged Sisters : studying the entrepreneurship and innovation support system from ‘within’
- 2013
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Konferensbidrag (refereegranskat)abstract
- Entrepreneurship and innovation support has grown into large institutions in a society that cherishes an enterprising culture. Individuals are encouraged to be entrepreneurial and innovative in general, and to start up their own companies in particular. To support individuals in their business creation processes, policy stresses the need of providing with measures. Together these measures comprise a support system, directed towards supporting new and established entrepreneurs. It has however been recognized that the entrepreneurship and innovation public support system is highly gendered, favoring men and male businesses, whilst programs targeting women put the onus on individual women to start and grow businesses. As well it has been recognized that the policy support system tends to exclude ‘othered’ groups rather than including them in enterprising activities. The subtext of entrepreneurship support points to how some people “are” entrepreneurs, whilst others need support in order to become more entrepreneurial. Hence, there is a need to change the support system of entrepreneurship and innovation since it tends to disempower rather than to empower ‘othered’ groups in society.“Sisters in Business” make up an organization of wo/men entrepreneurs who have joined forces to address this need. Their vision is that entrepreneurship should reflect the society at large. During the last year they have therefore taken several initiatives to make this happen and is today one of the support organizations in a medium sized Swedish town. In this paper three Sisters are working together with a researcher within this area. Together we have formed a group of “engaged sisters´”. In our dialogue the dichotomy between ‘practice’ and ‘theory’ have temporarily dissolved in favor of creating narratives, from episodes, experiences and the everyday life of sister´s, to illustrate how the support system works from ‘within’. This led us to questioning whether the ‘support system’ really is a support system, or something else? Furthermore, this insight made it apparent that there exists ‘other’ support system, tough concealed and silenced. Finally, suggestions are proposed for how ‘practitioners’ can work together with ‘academics’ to change the rules of the game.
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| 6. |
- Bestas, Burcu, et al.
(författare)
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Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model
- 2014
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:9, s. 4067-4081
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Tidskriftsartikel (refereegranskat)abstract
- X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.
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| 7. |
- Braem, Marieke G. M., et al.
(författare)
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Coffee and tea consumption and the risk of ovarian cancer : a prospective cohort study and updated meta-analysis
- 2012
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Ingår i: American Journal of Clinical Nutrition. - Bethesda : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 95:5, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% Cl: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer. Am J Clin Nutr 2012;95:1172-81.
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| 8. |
- Braem, Marieke G. M., et al.
(författare)
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Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
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| 9. |
- Englund, Mikael C. O., 1971, et al.
(författare)
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The establishment of 20 different human embryonic stem cell lines and subclones; a report on derivation, culture, characterisation and banking.
- 2010
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Ingår i: In vitro cellular & developmental biology. Animal. - : Springer Science and Business Media LLC. - 1543-706X .- 1071-2690. ; 46:3-4, s. 217-30
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Tidskriftsartikel (refereegranskat)abstract
- This report summarises our efforts in deriving, characterising and banking of 20 different human embryonic stem cell lines. We have derived a large number of human embryonic stem cell lines between 2001 and 2005. One of these cell lines was established under totally xeno-free culture conditions. In addition, several subclones have been established, including a karyoptypical normal clone from a trisomic mother line. A master cell banking system has been utilised in concert with an extensive characterisation programme, ensuring a supply of high quality pluripotent stem cells for further research and development. In this report we also present the first data on a proprietary novel antibody, hES-Cellect, that exhibits high specificity for undifferentiated hES cells. In addition to the traditional manual dissection approach of propagating hES cells, we here also report on the successful approaches of feeder-free cultures as well as single cell cultures based on enzymatic digestion. All culture systems used as reported here have maintained the hES cells in a karyotypical normal and pluripotent state. These systems also have the advantage of being the principal springboards for further scale up of cultures for industrial or clinical applications that would require vastly more cells that can be produced by mechanical means.
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| 10. |
- Eriksson, Tommy, et al.
(författare)
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ApoLänk decreases patient medication discrepancies at discharge: initial experience from a Swedish bedside pharmacy service
- 2013
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Ingår i: European Journal of Hospital Pharmacy: Science and Practice. - : BMJ. - 2047-9964 .- 2047-9956. ; 20:1, s. 54-56
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a working model so that dispensing pharmacists, patients and medical staff can work together to identify, solve and prevent problems associated with discharge prescriptions. Method: A routine was developed for communication between pharmacists, patients and medical staff and for dispensing drugs at the bedside. Hospital medication lists and prescriptions from the pharmacy and healthcare databases were simultaneously assessed. The study was carried out in two neurological wards in a Swedish university hospital. Results: Major shortcomings were identified in the coordination of pharmacy and healthcare records and in patients’ ability to take responsibility for their medication at discharge. Discussion between patients and staff allowed discrepancies in communication and documentation to be corrected. Cooperation between pharmacists and nurses was perceived as being very positive and important. Conclusions: The Apolänk service was appreciated by nurses, is almost cost neutral and reduces discrepancies that have the potential to cause patient harm.
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