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- Fyhrquist, N, et al.
(författare)
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Microbe-host interplay in atopic dermatitis and psoriasis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4703-
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
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- Anthoni, M, et al.
(författare)
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Smad3 regulates dermal cytokine and chemokine expression and specific antibody production in murine responses to a respiratory chemical sensitizer
- 2010
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 151:2, s. 155-167
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The cytokine transforming growth factor-β(TGF-β) has important regulatory roles in the immune system. To investigate the role of intact TGF-β signaling during the contact hypersensitivity (CHS) response to a respiratory allergen, we exposed Smad3–/– mice to topical trimellitic anhydride (TMA). <i>Methods:</i> CHS was induced by topical application of TMA. The swelling of the TMA-exposed ears was analyzed, and lymph node, ear tissue and skin biopsies were collected for RNA isolation, histology and histochemical analyses. Lymph node cell proliferation was measured and blood samples were collected for analysis of TMA-specific immunoglobulin. <i>Results:</i> Topical TMA exposure resulted in increased mRNA expression of proinflammatory and suppressive cytokines (IL-1β, TNF-α, IL-6, IFN-γ, IL-4, IL-10, IL-17, IL-23, TGF-β), chemokines (CXCL9, CXCL10, CCL24) and chemokine receptors (CCR7, CCR8, CXCR2), increased numbers of CD3+ T cells in ear tissue, and lymphadenopathy in the Smad3–/– mice. The IL-10 result was confirmed at the protein level by immunohistochemistry. However, the ear-swelling response and infiltration of eosinophils, F4/80+ cells, CD11c+ cells and mast cells were similar in the Smad3–/– mice compared to their wild-type (WT) siblings. While TMA-specific IgE was induced equally in the WT and Smad3–/– mice, the concentration of TMA-specific IgG2a was significantly lower in the Smad3–/– mice. <i>Conclusions:</i> The Smad3 molecule contributes significantly to the regulation of the cytokine and chemokine network during the CHS response to TMA. The lack of Smad3 resulted in a potent Th2 shift, confirmed by strongly impaired IgG2a levels.
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- Fyhrquist-Vanni, N, et al.
(författare)
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Contact dermatitis
- 2007
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Ingår i: Dermatologic clinics. - : Elsevier BV. - 0733-8635. ; 25:4, s. 613-
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Tidskriftsartikel (refereegranskat)
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- Graner, M., et al.
(författare)
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Cardiac steatosis in patients with dilated cardiomyopathy
- 2014
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:14
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Tidskriftsartikel (refereegranskat)abstract
- Objective Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. Limited data exist on cardiac adiposity in subjects with dilated cardiomyopathy (DCM). The aim of the study was to examine the components of cardiac steatosis and their relationship to LV structure and function in non-diabetic DCM patients. Methods Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy (MRS), and LV function, visceral adipose (VAT) and abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MRI in 10 non-diabetic men with DCM and in 20 controls. Results In face of comparable intra-abdominal fat depots, myocardial TG [0.41% (0.21-2.19) vs 0.86% (0.31-2.24), p=0.038] was markedly lower and epicardial (895 mm(2)+/- 110 vs 664 mm(2)+/- 180, p=0.002) and pericardial fat [2173 mm(2) (616-3673) vs 1168 mm(2) (266-2319), p=0.039] depots were larger in patients with DCM compared with controls. In subjects with DCM, the LV global function index was decreased to a greater extent than the LV EF [21%+/- 6 vs 34% (16-40)]. Conclusions Myocardial TG content decreased and epicardial and pericardial fat depots increased in non-diabetic subjects with DCM. Although recognised as a site of ectopic fat accumulation, the derangement of myocardial TG seems to play a specific role in the myocardial energy metabolism in congestive heart failure.
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- Koikkalainen, Juha R., et al.
(författare)
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Early familial dilated cardiomyopathy : identification with determination of disease state parameter from cine MR image data
- 2008
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Ingår i: Radiology. - : Radiological Society of North America, Inc. - 0033-8419 .- 1527-1315. ; 249:1, s. 88-96
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize early changes in cardiac anatomy and function for lamin A/C gene (LMNA) mutation carriers by using magnetic resonance (MR) imaging and to develop tools to analyze and visualize the findings.MATERIALS AND METHODS: The ethical review board of the institution approved the study, and informed written consent was obtained. The patient group consisted of 12 subjects, seven women (mean age, 36 years; age range, 18-54 years) and five men (mean age, 28 years; age range, 18-39 years) of Finnish origin, who were each heterozygotes with one LMNA mutation that may cause familial dilated cardiomyopathy (DCM). All the subjects were judged to be healthy with transthoracic echocardiography. The control group consisted of 14 healthy subjects, 11 women (mean age, 41 years; range, 23-54 years) and three men (mean age, 45 years; range, 34-57 years), of Finnish origin. Cine steady state free precession MR imaging was performed with a 1.5-T system. The volumes, wall thickness, and wall motion of both left ventricle (LV) and right ventricle were assessed. A method combining multiple MR image parameters was used to generate a global cardiac function index, the disease state parameter (DSP). A visual fingerprint was generated to assess the severity of familial DCM.RESULTS: The mean DSP of the patient group (0.69 +/- 0.15 [standard deviation]) was significantly higher than that of the control group (0.32 +/- 0.13) (P = .00002). One subject had an enlarged LV.CONCLUSION: Subclinical familial DCM was identified by determination of the DSP with MR imaging, and this method might be used to recognize familial DCM at an early stage.
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- Papadopoulos, Nikolaos G, et al.
(författare)
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Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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| 39. |
- Suojalehto, H, et al.
(författare)
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Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:19
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Tidskriftsartikel (refereegranskat)abstract
- A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.
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| 40. |
- Tiihonen, J, et al.
(författare)
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Genetic background of extreme violent behavior
- 2015
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 20:6, s. 786-792
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