| 1. |
- Bengtsson, Eva, et al.
(författare)
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ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.
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| 2. |
- de Zwarte, Sonja M. C., et al.
(författare)
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The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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| 3. |
- Goncalves, Isabel, et al.
(författare)
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High levels of cathepsin D and cystatin B are associated with increased risk of coronary events.
- 2016
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Ingår i: Open Heart. - : BMJ. - 2053-3624. ; 3:1, s. 000353-000353
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Tidskriftsartikel (refereegranskat)abstract
- The majority of acute coronary syndromes are caused by plaque ruptures. Proteases secreted by macrophages play an important role in plaque ruptures by degrading extracellular matrix proteins in the fibrous cap. Matrix metalloproteinases have been shown to be markers for cardiovascular disease whereas the members of the cathepsin protease family are less studied.
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| 4. |
- Hansson, Mikael, 1986-
(författare)
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Combinatorics and topology related to involutions in Coxeter groups
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation consists of three papers in combinatorial Coxeter group theory.A Coxeter group is a group W generated by a set S, where all relations can be derived from the relations s2 = e for all s ? S, and (ss′)m(s,s′) = e for some pairs of generators s ≠ s′ in S, where e ? W is the identity element and m(s, s′) is an integer satisfying that m(s, s′) = m(s′, s) ≥ 2. Two prominent examples of Coxeter groups are provided by the symmetric group Sn (i.e., the set of permutations of {1, 2, . . . , n}) and finite reflection groups (i.e., finite groups generated by reflections in some real euclidean space). There are also important infinite Coxeter groups, e.g., affine reflection groups.Every Coxeter group can be equipped with various natural partial orders, the most important of which is the Bruhat order. Any subset of a Coxeter group can then be viewed as an induced subposet.In Paper A, we study certain posets of this kind, namely, unions of conjugacy classes of involutions in the symmetric group. We obtain a complete classification of the posets that are pure (i.e., all maximal chains have the same length). In particular, we prove that the set of involutions with exactly one fixed point is pure, which settles a conjecture of Hultman in the affirmative. When the posets are pure, we give their rank functions. We also give a short, new proof of the EL-shellability of the set of fixed-point-free involutions, established by Can, Cherniavsky, and Twelbeck.Paper B also deals with involutions in Coxeter groups. Given an involutive automorphism θ of a Coxeter system (W, S), letℑ(θ) = {w ? W | θ(w) = w−1}be the set of twisted involutions. In particular, ℑ(id) is the set of ordinary involutions in W. It is known that twisted involutions can be represented by words in the alphabet = { | s ? S}, called -expressions. If ss′ has finite order m(s, s′), let a braid move be the replacement of ′ ⋯ by ′ ′ ⋯, both consisting of m(s, s′) letters. We prove a word property for ℑ(θ), for any Coxeter system (W, S) with any θ. More precisely, we provide a minimal set of moves, easily determined from the Coxeter graph of (W, S), that can be added to the braid moves in order to connect all reduced -expressions for any given w ? ℑ(θ). This improves upon a result of Hamaker, Marberg, and Pawlowski, and generalises similar statements valid in certain types due to Hu, Zhang, Wu, and Marberg.In Paper C, we investigate the topology of (the order complexes of) certain posets, called pircons. A special partial matching (SPM) on a poset is a matching of the Hasse diagram satisfying certain extra conditions. An SPM without fixed points is precisely a special matching as defined by Brenti. Let a pircon be a poset in which every non-trivial principal order ideal is finite and admits an SPM. Thus pircons generalise Marietti’s zircons. Our main result is that every open interval in a pircon is a PL ball or a PL sphere.An important subset of ℑ(θ) is the set ?(θ) = {θ(w−1)w | w ? W} of twisted identities. We prove that if θ does not flip any edges with odd labels in the Coxeter graph, then ?(θ), with the order induced by the Bruhat order on W, is a pircon. Hence, its open intervals are PL balls or spheres, which confirms a conjecture of Hultman. It is also demonstrated that Bruhat orders on Rains and Vazirani’s quasiparabolic W-sets (under a boundedness assumption) form pircons. In particular, this applies to all parabolic quotients of Coxeter groups.
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| 5. |
- Hansson, Mikael, 1986-
(författare)
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Generalised Ramsey numbers and Bruhat order on involutions
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of two papers within two different areas of combinatorics.Ramsey theory is a classic topic in graph theory, and Paper A deals with two of its most fundamental problems: to compute Ramsey numbers and to characterise critical graphs. More precisely, we study generalised Ramsey numbers for two sets Γ1 and Γ2 of cycles. We determine, in particular, all generalised Ramsey numbers R(Γ1, Γ2) such that Γ1 or Γ2 contains a cycle of length at most 6, or the shortest cycle in each set is even. This generalises previous results of Erdös, Faudree, Rosta, Rousseau, and Schelp. Furthermore, we give a conjecture for the general case. We also characterise many (Γ1, Γ2)-critical graphs. As special cases, we obtain complete characterisations of all (Cn,C3)-critical graphs for n ≥ 5, and all (Cn,C5)-critical graphs for n ≥ 6.In Paper B, we study the combinatorics of certain partially ordered sets. These posets are unions of conjugacy classes of involutions in the symmetric group Sn, with the order induced by the Bruhat order on Sn. We obtain a complete characterisation of the posets that are graded. In particular, we prove that the set of involutions with exactly one fixed point is graded, which settles a conjecture of Hultman in the affirmative. When the posets are graded, we give their rank functions. We also give a short, new proof of the EL-shellability of the set of fixed-point-free involutions, recently proved by Can, Cherniavsky, and Twelbeck.
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| 6. |
- Holmkvist, Petra, et al.
(författare)
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A major population of mucosal memory CD4(+) T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
- 2015
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:3, s. 545-558
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87.
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| 7. |
- Hultman, Karin, et al.
(författare)
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Cartilage Oligomeric Matrix Protein Associates With a Vulnerable Plaque Phenotype in Human Atherosclerotic Plaques
- 2019
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Ingår i: Stroke. - 1524-4628. ; 50:11, s. 3289-3292
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- Extracellular matrix proteins are important in atherosclerotic disease by influencing plaque stability and cellular behavior but also by regulating inflammation. COMP (cartilage oligomeric matrix protein) is present in healthy human arteries and expressed by smooth muscle cells. A recent study showed that transplantation of COMP-deficient bone marrow to apoE-/- mice increased atherosclerotic plaque formation, indicating a role for COMP also in bone marrow-derived cells. Despite the evidence of a role for COMP in murine atherosclerosis, knowledge is lacking about the role of COMP in human atherosclerotic disease. Methods- In the present study, we investigated if COMP was associated with a stable or a vulnerable human atherosclerotic plaque phenotype by analyzing 211 carotid plaques for COMP expression using immunohistochemistry. Results- Plaque area that stained positive for COMP was significantly larger in atherosclerotic plaques associated with symptoms (n=110) compared with asymptomatic plaques (n=101; 9.7% [4.7-14.3] versus 5.6% [2.8-9.8]; P=0.0002). COMP was positively associated with plaque lipids (r=0.32; P=0.000002) and CD68 cells (r=0.15; P=0.036) but was negatively associated with collagen (r=-0.16; P=0.024), elastin (r=-0.14; P=0.041), and smooth muscle cells (r=-0.25; P=0.0002). COMP was positively associated with CD163 (r=0.37; P=0.00000006), a scavenger receptor for hemoglobin/haptoglobin and a marker of Mhem macrophages, and with intraplaque hemorrhage, measured as glycophorin A staining (r=0.28; P=0.00006). Conclusions- The present study shows that COMP is associated to symptomatic carotid atherosclerosis, CD163-expressing cells, and a vulnerable atherosclerotic plaque phenotype in humans.
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| 8. |
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| 9. |
- Rattik, Sara, et al.
(författare)
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IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice.
- 2015
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 242:2, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- IL-22 is a recently discovered cytokine that belongs to the family of IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid cells and has been suggested to be involved in tissue repair. As both inflammation and repair play important roles in atherosclerosis we investigated if IL-22 deficiency influences the disease process in Apoe(-/-) mice.
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| 10. |
- Song, Huan, et al.
(författare)
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Waiting time for cancer treatment and mental health among patients with newly diagnosed esophageal or gastric cancer : A nationwide cohort study
- 2017
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Except for overall survival, whether or not waiting time for treatment could influences other domains of cancer patients' overall well-being is to a large extent unknown. Therefore, we performed this study to determine the effect of waiting time for cancer treatment on the mental health of patients with esophageal or gastric cancer. Methods: Based on the Swedish National Quality Register for Esophageal and Gastric Cancers (NREV), we followed 7,080 patients diagnosed 2006-2012 from the time of treatment decision. Waiting time for treatment was defined as the interval between diagnosis and treatment decision, and was classified into quartiles. Mental disorders were identified by either clinical diagnosis through hospital visit or prescription of psychiatric medications. For patients without any mental disorder before treatment, the association between waiting time and subsequent onset of mental disorders was assessed by hazard ratios (HRs) with 95% confidence interval (CI), derived from multivariable-adjusted Cox model. For patients with a preexisting mental disorder, we compared the rate of psychiatric care by different waiting times, allowing for repeated events. Results: Among 4,120 patients without any preexisting mental disorder, lower risk of new onset mental disorders was noted for patients with longer waiting times, i.e. 18-29 days (HR 0.86; 95% CI 0.74-1.00) and 30-60 days (HR 0.79; 95% CI 0.67-0.93) as compared with 9-17 days. Among 2,312 patients with preexisting mental disorders, longer waiting time was associated with more frequent psychiatric hospital care during the first year after treatment (37.5% higher rate per quartile increase in waiting time; p for trend = 0.0002). However, no such association was observed beyond one year nor for the prescription of psychiatric medications. Conclusions: These data suggest that waiting time to treatment for esophageal or gastric cancer may have different mental health consequences for patients depending on their past psychiatric vulnerabilities. Our study sheds further light on the complexity of waiting time management, and calls for a comprehensive strategy that takes into account different domains of patient well-being in addition to the overall survival.
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