| 1. |
- Edsjö, Anders, et al.
(författare)
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Building a precision medicine infrastructure at a national level : The Swedish experience
- 2023
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Ingår i: Cambridge Prisms: Precision Medicine. - : Cambridge University Press. - 2752-6143. ; 1
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.
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| 2. |
- Eskling, Marie, et al.
(författare)
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Enzymes and mechanisms for violaxanthin-zeaxanthin conversion
- 2001
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Ingår i: Regulation of photosynthesis. - Dordrecht : Springer Netherlands. - 0792363329 ; , s. 433-452
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The xanthophyll cycle is of great importance in relation to light stress. Particularly, interest has been focused on the possible photoprotective role of zeaxanthin. In higher plants under light stress, zeaxanthin is formed from violaxanthin in a reaction catalyzed by violaxanthin de-epoxidase (VDE). The reverse reaction is catalyzed by zeaxanthin epoxidase (ZE) under low light or in darkness. VDE has been purified from spinach and lettuce as a 43-kDa protein. The gene has been cloned and sequenced from several species, and a few mutants have been isolated. The gene is nuclear encoded and the transit peptide is characteristic for targeting to the thylakoid lumen. The activity of VDE is affected by factors such as a pH-dependent binding to the thylakoid membrane, concentration of ascorbic acid, temperature and availability of violaxanthin in relation to amount, type and distribution of pigment-protein complexes in the membrane. The information about ZE is more limited. The enzyme has not yet been isolated but its gene has been cloned and sequenced and a number of mutants have been isolated. The role of the xanthophyll cycle in the dissipation of excess light energy will be discussed particularly in relation to the recent progress in studies on various mutants. The possible role of the xanthophyll cycle in other processes, such as protection against oxidative stress of lipids, regulation of membrane fluidity, participation in blue light responses, and regulation of abscisic acid synthesis will also be presented.
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| 3. |
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| 4. |
- Gisselsson, Anna, et al.
(författare)
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Chemical and mutational modification of histidines in violaxanthin de-epoxidase from Spinachcia oleracea.
- 2003
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Ingår i: Physiologia Plantarum. - : Wiley. - 0031-9317. ; 119:1, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- The violaxanthin de-epoxidase (VDE) gene from spinach (Spinacia oleracea) was cloned, sequenced (GenBank AJ 250433), and expressed in Escherichia coli. The highest obtained conversion rate of violaxanthin was 86 nmol s-1 per litre of growth medium, corresponding to an amount of active enzyme of 0.4 mg l-1. Sequence comparison between VDE from different species were made and particular interest was focused on four highly conserved histidines (H121,124,167,173) and their possible involvement in enzymatic activity. Chemical modification of the histidines using DEPC or by site-directed mutations resulted in partial or total inactivation of the enzyme. The chemical modification could be reversed by hydroxylamine treatment, regenerating a large percentage of the original activity. The histidine residues, which are located in pairs close to each other, were pairwise substituted for either alanine or arginine. This resulted in one inactive mutant (H121,124R) and three mutants with very different activities and decreased binding of ascorbic acid, as reflected by an up to four-fold increase in Km. A substitution of all four histidines for either alanine or arginine resulted in inactive enzymes. Based on these results it is suggested that the histidine residues are important for the activity of VDE.
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| 5. |
- Gisselsson, A, et al.
(författare)
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Role of histidines in the binding of violaxanthin de-epoxidase to the thylakoid membrane as studied by site-directed mutagenesis
- 2004
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Ingår i: Physiologia Plantarum. - : Wiley. - 0031-9317 .- 1399-3054. ; 122:3, s. 337-343
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of violaxanthin de-epoxidase (VDE) involves a conformational change at low lumenal pH, followed by binding of the enzyme to the thylakoid membrane. The role of histidine residues in this process was studied by release of unbound enzyme from thylakoids upon sonication, on a pH scale from 4.7 to 7.1. The co-operativity for binding of spinach VDE (four histidines) to the membrane was found to be 3.8, with respect to protons, and had an inflexion point at pH 6.6, whereas VDE from wheat (three histidines) showed a co-operativity of 2.9 and had an inflexion point at pH 6.2. Mutant forms of VDE were constructed and probed for their binding to the outside of thylakoid membranes. With one or two histidines substituted for alanine or arginine, a lower co-operativity (1.6-2.3) was found, compared with the wild type. Based on these findings, and that the pKa value for histidine is within the range where the VDE binding takes place, we propose that protonation of the histidine residues at low pH induces the conformational change of VDE, and hence indirectly regulates binding of the enzyme to the thylakoid membrane.
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| 6. |
- Gisselsson, Hans, et al.
(författare)
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Approximal caries increment in two cohorts of schoolchildren after discontinuation of a professional flossing program with chlorhexidine gel.
- 2005
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Ingår i: Caries research. - : S. Karger AG. - 0008-6568 .- 1421-976X. ; 39:5, s. 350-6
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Tidskriftsartikel (refereegranskat)abstract
- We have in two earlier studies evaluated the effect of professional flossing with chlorhexidine (CHX) gel treatment, in 4- to 7-year-old preschool children and in 12- to 15-year-old teenagers. The mean caries reduction after 3 years was around 40% compared to placebo gel or no gel treatment. The aim of the present investigation was to follow up these two clinical studies. The preschool children were followed up to the age of 16 years and the teenager group to the age of 19. Of the total number of original children, 71 and 80% were available at the age of 16 and 19 years, respectively. At the 9-year follow-up, when the children were 16 years old, the former CHX group had still significantly lower mean DFS than the control group (p < 0.05). The differences in caries increment occurred between 7 and 12 years of age, whereas the number of new caries lesions during the next 4 years were almost the same in the three groups. At the 4-year follow-up, when the teenagers were 19 years old, DFS was 6.9 in the former CHX group compared to 10.4 in the control group (p < 0.05). The main conclusion of these two follow-up studies after 9 and 4 years, respectively, is that caries reductions obtained at the end of professional flossing with a 1% CHX gel were maintained.
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| 7. |
- Jin, Charlotte, et al.
(författare)
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Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH
- 2001
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 30:2, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.
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| 8. |
- Lindquist, Birgitta, 1952, et al.
(författare)
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Effect of chlorhexidine gel on approximalcaries increment in adolescents with high caries risk using professional flossing compared to individual trays
- 2010
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Ingår i: Swedish Dental Journal. - 0347-9994. ; 34:1, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the effect of chlorhexidine gel treatment on approximal caries development during a three year-study in children with expected high risk of caries. New caries of this group was compared to the caries development in two groups with assumed moderate or low caries risk. One hundred and sixty-nine of 201 twelve-year-old children fulfilled the trial. A group of 77 children showed no caries experience and was expected to be a low caries risk group (R1). Ninety-two children had at least one approximal lesion and their salivary numbers of mutans streptococci (ms) were quantified. Forty-six of those showed less than 3 x 10(5) ms per ml saliva and were supposed to have a moderate caries risk (R2). Forty-six children, with high levels of ms, were expected to have a high caries risk (R3). Both R1 and R3 were treated with fluoride varnish every 18th month and R2 every 6th month. The R3 group was supplementary treated with 1% chlorhexidine gel (Corsodyl) by using either flossing combined with polishing (Flossing group), or gel in individual trays (Tray group) every third month, in two subsequent days. The mean caries development during three years was for R1 and R2, 1.5 and 3.0, respectively. For R3, the corresponding caries incidence was 2.9 in the Tray group and 2.8 in the Flossing group. Significantly less new caries was found in the R1 compared to R2 and R3, but no significant difference was found between R2 and R3 or between the two groups of R3. In conclusion both methods of professional chlorhexidine gel treatments showed a caries development corresponding to the group with moderate caries risk and could both be used for caries prevention.
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