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Sökning: WFRF:(Hansson Karl Johan)

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1.
  • Hansson, Jonas, et al. (författare)
  • Biomarkers of Extracellular Matrix Metabolism (MMP-9 and TIMP-1) and Risk of Stroke, Myocardial Infarction, and Cause-Specific Mortality Cohort Study
  • 2011
  • Ingår i: PLoS ONE. - 1932-6203. ; 6:1, s. e16185
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991-1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03-1.19; and 1.11, 1.02-1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09-1.37; and 1.18, 1.04-1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.
2.
  • Skillbäck, Tobias, et al. (författare)
  • A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease
  • 2017
  • Ingår i: Scientific Reports. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166 demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.
3.
  • Alsanius, Beatrix, et al. (författare)
  • Ett steg närmare mars
  • 2006
  • Ingår i: Viola. - 0042-6407. ; 24, s. 44-45
  • Tidskriftsartikel (populärvet., debatt m.m.)
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  • Hansson, Karl, 1985-, et al. (författare)
  • Expanding the cerebrospinal fluid endopeptidome
  • 2017
  • Ingår i: Proteomics. - 1615-9853. ; 17:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Biomarkers of neurodegenerative disorders are needed to assist in diagnosis, to monitor disease progression and therapeutic interventions, and to provide insight into disease mechanisms. One route to identify such biomarkers is by proteomic and peptidomic analysis of cerebrospinal fluid (CSF). In the current study, we performed an in-depth analysis of the human CSF endopeptidome to establish an inventory thatmay serve as a basis for future targeted biomarker studies. High-pH RP HPLC was employed for off-line sample prefractionation followed by low-pH nano-LC-MS analysis. Different software programs and scoring algorithms for peptide identification were employed and compared. A total of 18 031 endogenous peptides were identified at a FDR of 1%, increasing the number of known endogenous CSF peptides 10fold compared to previous studies. The peptides were derived from 2 053 proteins of which more than 60 have been linked to neurodegeneration. Notably, among the findings were six peptides derived from microtubule-associated protein tau, three of which span the diagnostically interesting threonine-181 (Tau-F isoform). Also, 213 peptides from amyloid precursor protein were identified, 58 of which were partially or completely within the sequence of amyloid beta 1-40/42, as well as 109 peptides from apolipoprotein E, spanning sequences that discriminate between the E2/E3/E4 isoforms of the protein.
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8.
  • Nordquist, Birgitta, et al. (författare)
  • Peoples experience of the indoor climate in wind exposed apartments
  • 2010
  • Ingår i: [Host publication title missing]. - Proceedings of Buildair 2012.
  • Konferensbidrag (refereegranskat)abstract
    • Apartment buildings have been built in a wind exposed area situated close to the seaside in Malmö, Sweden. Several goals when building these apartments have been articulated, for example low energy usage, validation of the leakage factor and a satisfying indoor environment. The purpose of this study is to examine how the people living in the apartments experience the indoor climate. Their experience has been studied by a questionnaire. 201 persons have responded to the questionnaire. The overall result in terms of indoor climate and health experience shows a sufficient experience of the indoor climate. One interesting finding is that a factor related to the air-tightness; the experience of draught stands out. The apartments have also been divided into sub-groups and one finding has been that the people in the apartments exposed to wind, the outer layer of the city block, experience a doubled amount of draught compared to the people living inside the city block and sheltered from wind. The results may also be interpretated as that if a building is planned to be built in wind exposed surroundings this issue should be addressed and that a tight building is important to build, also for indoor climate reasons.
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9.
  • Russell, Claire L, et al. (författare)
  • Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates.
  • 2016
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 55:1, s. 303-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Aberrant tau phosphorylation is a hallmark in Alzheimer's disease (AD), believed to promote formation of paired helical filaments, the main constituent of neurofibrillary tangles in the brain. While cerebrospinal fluid (CSF) levels of total tau and tau phosphorylated at threonine residue 181 (pThr181) are established core biomarkers for AD, the value of alternative phosphorylation sites, which may have more direct relevance to pathology, for early diagnosis is not yet known, largely due to their low levels in CSF and lack of standardized detection methods. To overcome sensitivity limitations for analysis of phosphorylated tau in CSF, we have applied an innovative mass spectrometry (MS) workflow, TMTcalibratortrademark, to enrich and enhance the detection of phosphoproteome components of AD brain tissue in CSF, and enable the quantitation of these analytes. We aimed to identify which tau species present in the AD brain are also detectable in CSF and which, if any, are differentially regulated with disease. Over 75% coverage of full-length (2N4R) tau was detected in the CSF with 47 phosphopeptides covering 31 different phosphorylation sites. Of these, 11 phosphopeptides were upregulated by at least 40%, along with an overall increase in tau levels in the CSF of AD patients relative to controls. Use of the TMTcalibratortrademark workflow dramatically improved our ability to detect tau-derived peptides that are directly related to human AD pathology. Further validation of regulated tau peptides as early biomarkers of AD is warranted and is currently being undertaken.
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