| 1. |
- Abel, Frida, 1974, et al.
(författare)
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A 6-gene signature identifies four molecular subgroups of neuroblastoma
- 2011
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Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p
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| 2. |
- Abel, Frida, 1974, et al.
(författare)
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Imbalance of the mitochondrial pro- and anti-apoptotic mediators in neuroblastoma tumours with unfavourable biology.
- 2005
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Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 0959-8049. ; 41:4, s. 635-46
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that a lack of apoptosis plays an important role in neuroblastoma (NB) progression. We therefore screened cDNA array filters, including 198 apoptotic genes, in order to identify mRNA transcripts that are differentially expressed in tumours with unfavourable versus favourable biology. Twenty-one genes were analysed further using real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Significantly lower levels of DNCL1 (PIN; P(c)(corrected) = 0.0054) and NTRK1 (TrkA; P(c) = 0.039) were found in NB tumours with unfavourable biology. In addition, BID, BCL2, APAF1, CASP2, CASP3 and CASP9 were found to be preferentially expressed in tumours with favourable biology, whereas CDKN1A (p21), IL2RA, and MCL1, were found to be preferentially expressed in NB tumours with unfavourable biology. In conclusion, mRNA levels of transcripts encoding pro-apoptotic mediators of the mitochondrial apoptotic pathway were found to be expressed to a lower extent in tumours with unfavourable biology. Our data also suggest that the mitochondrial pathway is suppressed in advanced stages of NB tumours, due to an imbalance between anti-apoptotic and pro-apoptotic mediators which is a finding that may have therapeutic significance.
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| 3. |
- Abel, Frida, 1974, et al.
(författare)
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Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors.
- 2004
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Ingår i: International journal of oncology. - 1019-6439 .- 1791-2423. ; 25:5, s. 1297-302
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Tidskriftsartikel (refereegranskat)abstract
- DFF45 has essential functions in the final stage of apoptosis by acting both as a folding chaperone and a DNase inhibitor of DFF40. The gene encoding DFF45 (DFFA) maps to the consensus deleted region in primary neuroblastoma (NB; 1p36.2-3) and within the homozygously deleted region in an NB cell line (1p36.2). DFF45 is therefore an attractive candidate NB tumor suppressor. In a previous study we found a rare allele variant, causing a non-polar to a polar amino acid exchange (Ile69Thr) in a preserved hydrophobic patch of DFF45, and we also found DFFA to be preferentially expressed in favorable NB tumors. We have extended the previous study and performed mutation analyses in another 56 NB tumors (100 in total) as well as a set of other tumors for coding mutations in DFFA. We have also performed studies of the DFFA expression in tumors using real-time PCR. We found a missense mutation (Ile15Met) in the remaining allele of a teratoma with heterozygous deletion of 1p, and a three base-pair deletion in an NB of unknown stage causing a deletion of amino acid 37 in DFF45. The one-base substitution detected in the teratoma was not present in the patients constitutional DNA, i.e. it is a true mutation present in the tumor DNA only. In conclusion, three different coding alterations have been found in the region encoding the N-terminal regulatory domain of DFF45, responsible for binding and achieving its chaperone and inhibitor functions on other proteins. Moreover, by real-time RT-PCR expression study, we found the mRNA level of DFFA to be significantly (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome.
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| 4. |
- Abrahamsson, Hasse, 1943, et al.
(författare)
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Familial intestinal degenerative neuropathy with chronic intestinal pseudo-obstruction linked to a gene locus with duplication in chromosome 9
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 54:12, s. 1441-1447
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intestinal degenerative neuropathy without extra-intestinal involvement occurs as familial forms (FIDN) but the genetics behind is unknown. We studied a Swedish family with autosomal dominant disease and several cases of chronic intestinal pseudo-obstruction (CIP). Methods: We included 33 members of a family sharing a male ancestor. Chronic intestinal symptoms including diarrhoea occurred in 11, four had severe CIP. DNA was analysed with SNP-microarray (Affymetrix), linkage (Allegro Software) and gene dosage (CNAG 3.0). Results: Genetic linkage was found to the short arm of Ch9 to a 9.7 Mb region with 45 protein-coding genes, 22 of which were duplicated (1.2 Mb duplication) (dup(9)(p21.3) with breaking point in the FOCAD-gene. Lod score for the region was 3.4. Fourteen subjects were duplication carriers including all 11 subjects having severe chronic symptoms/CIP. Nineteen subjects had no duplication. The occurrence of gastrointestinal symptoms in the family was strongly linked to duplication carrier-ship (p = .0005). The two branches of the family had separate maternal ancestors (A and B). Including the previous generation, severe disease (overt CIP and/or death from intestinal failure) was assessed to occur in 100% (5/5) of duplication carriers in branch A and in 21% (3/14) in branch B (p = .005). In branch B the onset of symptoms was later (median 38 vs. 24 yrs) and three duplication carriers were symptom-free. Conclusions: In this family with autosomal dominant hereditary intestinal neuropathy, the disorder is linked to a 9.7 Mb region in Ch9 including a 1.2 Mb duplication. There is a significant difference in disease expressivity between family branches, seemingly related to separate maternal ancestors.
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| 5. |
- Adamovic, Svetlana, 1965, et al.
(författare)
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Association study of IL2/IL21 and FcgRIIa: significant association with the IL2/IL21 region in Scandinavian coeliac disease families
- 2008
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Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 9:4, s. 364-367
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Tidskriftsartikel (refereegranskat)abstract
- The first genome-wide association study performed in a UK coeliac disease (CD) case-control cohort revealed association with a linkage disequilibrium block containing the KIAA1109/Tenr/IL2/IL21 genes. Also recently, an association with a non-synonymous polymorphism in Fcitalic gammaRIIa (CD32a) was reported in CD with an unusually strong P-value. We aimed to replicate the reported associations with the single nucleotide polymorphisms rs13119723 A>G and rs6822844 G>T in the KIAA1109/Tenr/IL2/IL21 region and rs1801274 G>A in the Fcitalic gammaRIIa gene in a family sample consisting of 325 Swedish/Norwegian families using the robust transmission disequilibrium test. The family sample used in this study included 100 families with two or more children affected by CD and 225 families with one affected child. We could confirm significant association between the polymorphisms rs13119723 A>G and rs6822844 G>T located in the KIAA1109/Tenr/IL2/IL21 region and CD (P-value 0.001 and 0.002, respectively). However, we found no association with the Fcitalic gammaRIIa rs1801274 G>A polymorphism (P-value=0.3). In conclusion, our results support the KIAA1109/Tenr/IL2/IL21 region as a true CD susceptibility region.
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| 6. |
- Adamovic, Svetlana, 1965, et al.
(författare)
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Fine mapping study in Scandinavian families suggests association between coeliac disease and haplotypes in chromosome region 5q32.
- 2008
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Ingår i: Tissue Antigens. - : Wiley. - 1399-0039 .- 0001-2815. ; 71:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- The previous genome-wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31–33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two-step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, Pnc = 4 × 10−5 at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (Pnc < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (Pnc = 2 × 10−6) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.
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| 7. |
- Adolfsson, Peter, 1963, et al.
(författare)
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Continuous glucose monitoring system during physical exercise in adolescents with type 1 diabetes
- 2011
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:12, s. 1603-1609
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Continuous glucose monitoring system (CGMS) provides detailed information on glucose fluctuations. The aim was to establish whether CGMS could be used during physical exercise and whether it detects more episodes of hypoglycaemia and hyperglycaemia than frequent blood glucose measurements. Methods: Adolescents with type 1 diabetes (12 girls and 47 boys) participated in three annual sports camps that lasted for 3-4 days and included different types of exercise: soccer, floorball + cross-country skiing and golf. During the study, blood glucose values, mean 8.7 +/- 3.3 per day, were obtained with Hemocue in parallel with the CGMS. Results: Ninety-eight per cent of the participants used the sensor at all times during the camps. Eighty-seven per cent of the sensors gave adequate signals for 24 h and 66% for 48 h. Median durations of hypoglycaemia and hyperglycaemia were 1.7 h per day and 3.8 h per day, respectively. The CGMS identified significantly more episodes of hypoglycaemia (p < 0.005) and hyperglycaemia (p < 0.005) during the day and night than frequent blood glucose tests. Conclusion: We demonstrate that, even during days that included episodic strenuous physical exercise, CGMS could provide useful information on glucose fluctuations during day and night, albeit with significant failure rates.
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| 8. |
- Adolfsson, Peter, 1963, et al.
(författare)
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Hormonal response during physical exercise of different intensities in adolescents with type 1 diabetes and healthy controls.
- 2012
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 13:8, s. 587-96
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Tidskriftsartikel (refereegranskat)abstract
- Background Physical activity is a critical component in the care of diabetes. Although it offers health benefits it presents challenges. Objective To investigate differences between adolescent boys and girls with type 1 diabetes and healthy controls in terms of maximal work capacity (VO2 max) and hormonal response to physical exercise of different intensities. Subjects Twelve individuals (six boys and six girls; age 1419 yr, pubertal stage 45) with type 1 diabetes (duration, 6.3 +/- 4.4 yr; hemoglobin A1c, 63 +/- 10 mmol/mol) were compared with 12 healthy controls matched for age, sex, pubertal stage, body mass index standard deviation score, and amount of regular physical activity. Methods During consecutive days, three different workloads; maximal, endurance, and interval, were performed on an Ergometer cycle. During the tests, levels of lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous glucose was measured continuously. Results VO2 max did not differ between the groups, diabetes 49.8 +/- 9.9 vs. control 50.7 +/- 12.0 mL/min/kg. Hormonal responses did not differ between the groups except for mean peak GH level during the interval test, diabetes 63.2 +/- 27.0 vs. control 33.8 +/- 20.9 mU/L, p
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| 9. |
- Ahlgren, Erika, et al.
(författare)
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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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| 10. |
- Ahlin, Kristina, et al.
(författare)
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Antecedents and neuroimaging patterns in cerebral palsy with epilepsy and cognitive impairment: a population-based study in children born at term
- 2017
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 96:7, s. 828-836
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Antecedents of accompanying impairments in cerebral palsy and their relation to neuroimaging patterns need to be explored. Material and methods. A population-based study of 309 children with cerebral palsy born at term between 1983 and 1994. Prepartum, intrapartum, and postpartum variables previously studied as antecedents of cerebral palsy type and motor severity were analyzed in children with cerebral palsy and cognitive impairment and/or epilepsy, and in children with cerebral palsy without these accompanying impairments. Neuroimaging patterns and their relation to identified antecedents were analyzed. Data were retrieved from the cerebral palsy register of western Sweden, and from obstetric and neonatal records. Results. Children with cerebral palsy and accompanying impairments more often had low birthweight (kg) (odds ratio 0.5, 95% confidence interval 0.3-0.8), brain maldevelopment known at birth (p = 0.007, odds ratio infinity) and neonatal infection (odds ratio 5.4, 95% confidence interval 1.04-28.4). Moreover, neuroimaging patterns of maldevelopment (odds ratio 7.2, 95% confidence interval 2.9-17.2), cortical/subcortical lesions (odds ratio 5.3, 95% confidence interval 2.3-12.2) and basal ganglia lesions (odds ratio 7.6, 95% confidence interval 1.4-41.3) were more common, wheras white matter injury was found significantly less often (odds ratio 0.2, 95% confidence interval 0.1-0.5). In most children with maldevelopment, the intrapartum and postpartum periods were uneventful (p
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