| 1. |
- Odeberg, Jacob, et al.
(author)
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The influence of smoking and impaired glucose homoeostasis on the outcome in patients presenting with an acute coronary syndrome : a cross-sectional study
- 2014
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In: BMJ Open. - : BMJ. - 2044-6055. ; 4:7, s. e005077-
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Journal article (peer-reviewed)abstract
- Objectives: Smoking, diabetes, male sex, hypercholesterolaemia and hypertension are well-established risk factors for the development of coronary artery disease (CAD). However, less is known about their role in influencing the outcome in the event of an acute coronary syndrome (ACS). The aim of this study was to determine if these risk factors are associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with suspected ACS. Design: Cross-sectional study. Setting: Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992-1996). Participants: From 5292 patients admitted to the coronary care unit, 908 patients aged 30-74 years were selected, who at discharge had received the diagnosis of either MI (527) or UA (381). A control group consisted of 948 patients aged 30-74 years in whom a diagnosis of ACS was excluded. Main outcome measures: MI or UA. Results: Current smoking (OR 2.42 (1.61 to 3.62)), impaired glucose homoeostasis defined as glycated haemoglobin >= 5.5% + blood glucose >= 7.5 mM (OR 1.78 (1.19 to 2.67)) and male sex (OR 1.71 (1.21 to 2.40)) were significant factors predisposing to MI over UA, in the event of an ACS. Compared with the non-ACS group, impaired glucose homoeostasis, male sex, cholesterol level and age were significantly associated with development of an ACS (MI and UA). Interestingly, smoking was significantly associated with MI (OR 2.00 (1.32 to 3.02)), but not UA. Conclusions: Smoking or impaired glucose homoeostasis is an acquired risk factor for a severe ACS outcome in patients with CAD. Importantly, smoking was not associated with UA, suggesting that it is not a risk factor for all clinical manifestations of CAD, but its influence is important mainly in the acute stages of ACS. Thus, on a diagnosis of CAD, the cessation of smoking and management of glucose homoeostasis are of upmost importance to avoid severe subsequent ACS consequences.
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| 3. |
- Bergendal, Annica, et al.
(author)
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Risk factors for venous thromboembolism in pre- and postmenopausal women
- 2012
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:4, s. 596-601
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Journal article (peer-reviewed)abstract
- IntroductionHemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women.MethodIn a nationwide case–control study we included as cases 1470 women, 18 to 64 years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThe ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status.ConclusionMenopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.
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| 4. |
- Bruzelius, Maria, et al.
(author)
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Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism
- 2014
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:2, s. 426-432
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Journal article (peer-reviewed)abstract
- Introduction: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n = 2753) from Sweden. Materials and Methods: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
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| 6. |
- Fagerberg, Linn, et al.
(author)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Journal article (peer-reviewed)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 7. |
- Fagerberg, Linn, et al.
(author)
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Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
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Journal article (peer-reviewed)abstract
- A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
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| 8. |
- Habuka, Masato, et al.
(author)
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The Kidney Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e116125-
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Journal article (peer-reviewed)abstract
- To understand renal functions and disease, it is important to define the molecular constituents of the various compartments of the kidney. Here, we used comparative transcriptomic analysis of all major organs and tissues in the human body, in combination with kidney tissue micro array based immunohistochemistry, to generate a comprehensive description of the kidney-specific transcriptome and proteome. A special emphasis was placed on the identification of genes and proteins that were elevated in specific kidney subcompartments. Our analysis identified close to 400 genes that had elevated expression in the kidney, as compared to the other analysed tissues, and these were further subdivided, depending on expression levels, into tissue enriched, group enriched or tissue enhanced. Immunohistochemistry allowed us to identify proteins with distinct localisation to the glomeruli (n=11), proximal tubules (n=120), distal tubules (n=9) or collecting ducts (n=8). Among the identified kidney elevated transcripts, we found several proteins not previously characterised or identified as elevated in kidney. This description of the kidney specific transcriptome and proteome provides a resource for basic and clinical research to facilitate studies to understand kidney biology and disease.
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| 9. |
- Iglesias, Maria Jesus, et al.
(author)
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Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2, s. e32306-
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Journal article (peer-reviewed)abstract
- Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of upregulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.
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| 10. |
- Li, A., et al.
(author)
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Heart research advances using database search engines, human protein atlas and the sydney heart bank
- 2013
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In: Heart, Lung and Circulation. - : Elsevier BV. - 1443-9506 .- 1444-2892. ; 22:10, s. 819-826
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Research review (peer-reviewed)abstract
- This Methodological Review is intended as a guide for research students who may have just discovered a human "novel" cardiac protein, but it may also help hard-pressed reviewers of journal submissions on a "novel" protein reported in an animal model of human heart failure. Whether you are an expert or not, you may know little or nothing about this particular protein of interest. In this review we provide a strategic guide on how to proceed. We ask: How do you discover what has been published (even in an abstract or research report) about this protein? Everyone knows how to undertake literature searches using PubMed and Medline but these are usually encyclopaedic, often producing long lists of papers, most of which are either irrelevant or only vaguely relevant to your query. Relatively few will be aware of more advanced search engines such as Google Scholar and even fewer will know about Quertle. Next, we provide a strategy for discovering if your "novel" protein is expressed in the normal, healthy human heart, and if it is, we show you how to investigate its subcellular location. This can usually be achieved by visiting the website "Human Protein Atlas" without doing a single experiment. Finally, we provide a pathway to discovering if your protein of interest changes its expression level with heart failure/disease or with ageing.
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