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| 2. |
- Gu, Gucci Jijuan, 1984-, et al.
(author)
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Elevated MARK2-Dependent Phosphorylation of Tau in Alzheimer's Disease
- 2013
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:3, s. 699-713
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Journal article (peer-reviewed)abstract
- The appearance of neurofibrillary tangles (NFT), one of the major hallmarks of Alzheimer's disease (AD), is most likely caused by inappropriate phosphorylation and/or dephosphorylation of tau, eventually leading to the accumulation of NFTs. Enhanced phosphorylation of tau on Ser(262) is detected early in the course of the disease and may have a role in the formation of tangles. Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). Furthermore, we observed elevated interactions between MARK2 and tau in post-mortem human AD brains, compared to samples from non-demented elderly controls. Our results from transfected cells demonstrate a specific interaction between MARK2 and tau, as well as MARK2-dependent phosphorylation of tau at Ser(262). Furthermore, the elevated interactions between MARK2 and tau in AD brain sections suggests that MARK2 may play an important role in early phosphorylation of tau in AD, possibly qualifying as a therapeutic target for intervention to prevent disease progression.
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| 3. |
- Hallén, Magnus, et al.
(author)
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Male infertility after mesh hernia repair : a prospective study
- 2011
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In: Surgery. - : Elsevier. - 0039-6060 .- 1532-7361. ; 149:2, s. 179-184
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Journal article (peer-reviewed)abstract
- BACKGROUND: Several animal studies have raised concern about the risk for obstructive azoospermia owing to vasal fibrosis caused by the use of alloplastic mesh prosthesis in inguinal hernia repair. The aim of this study was to determine the prevalence of male infertility after bilateral mesh repair.METHODS: In a prospective study, a questionnaire inquiring about involuntary childlessness, investigation for infertility and number of children was sent by mail to a group of 376 men aged 18-55 years, who had undergone bilateral mesh repair, identified in the Swedish Hernia Register (SHR). Questionnaires were also sent to 2 control groups, 1 consisting of 186 men from the SHR who had undergone bilateral repair without mesh, and 1 consisting of 383 men identified in the general population. The control group from the SHR was matched 2:1 for age and years elapsed since operation. The control group from the general population was matched 1:1 for age and marital status.RESULTS: The overall response rate was 525 of 945 (56%). Method of approach (anterior or posterior), type of mesh, and testicular status at the time of the repair had no significant impact on the answers to the questions. Nor did subgroup analysis of the men CONCLUSION: The results of this prospective study in men do not support the hypothesis that bilateral inguinal hernia repair with alloplastic mesh prosthesis causes male infertility at a significantly greater rate than those operated without mesh.
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| 4. |
- Nilsson, Martin P., et al.
(author)
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BRCAsearch : written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer
- 2018
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 168:1, s. 117-126
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. Methods: In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. Results: During the period Feb 2, 2015–Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. Conclusions: Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.
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| 5. |
- Persson, Lena, 1951-, et al.
(author)
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Framväxt av en forskningsplattform
- 2013
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In: Aktionsforskning i vård och omsorg. - Malmö : Gleerups Utbildning AB. - 9789140685643 ; , s. 173-180
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Book chapter (pop. science, debate, etc.)
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| 6. |
- Persson, Lena, et al.
(author)
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Framväxt av en forskningsplattform
- 2013
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In: Aktionsforskning i vård och omsorg. - Malmö : Gleerups Utbildning AB. ; , s. 173-180
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Book chapter (other academic/artistic)
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| 9. |
- Rohlin, Anna, et al.
(author)
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Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing
- 2017
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In: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 16:2, s. 195-203
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Journal article (peer-reviewed)abstract
- Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or had a phenotype consistent with a known CRC syndrome. The purpose of the study was to demonstrate the diagnostic difficulties linked to genotype-phenotype diversity and the benefits of using a gene panel. Pathogenicity classification was carried out on 46 detected variants. In total we detected sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication in CDH1 intron1.
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| 10. |
- von Stedingk, Kristoffer, et al.
(author)
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Prevalence of germline pathogenic variants in 22 cancer susceptibility genes in Swedish pediatric cancer patients
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Up to 10% of pediatric cancer patients harbor pathogenic germline variants in one or more cancer susceptibility genes. A recent study from the US reported pathogenic variants in 22 out of 60 analyzed autosomal dominant cancer susceptibility genes, implicating 8.5% of pediatric cancer patients. Here we aimed to assess the prevalence of germline pathogenic variants in these 22 genes in a population-based Swedish cohort and to compare the results to those described in other populations. We found pathogenic variants in 10 of the 22 genes covering 3.8% of these patients. The prevalence of TP53 mutations was significantly lower than described in previous studies, which can largely be attributed to differences in tumor diagnosis distributions across the three cohorts. Matched family history for relatives allowed assessment of familial cancer incidence, however, no significant difference in cancer incidence was found in families of children carrying pathogenic variants compared to those who did not.
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