| 1. |
- Lindberg, Erika, 1979, et al.
(författare)
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Impaired activation of IFN-gamma+CD4+ T cells in peripheral blood of patients with dilated cardiomyopathy
- 2010
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Ingår i: Cellular Immunology. - San Diego, USA : Elsevier. - 0008-8749 .- 1090-2163. ; 263:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Viral persistence and autoantibodies are pathogenic components in patients with idiopathic dilated cardiomyopathy (DCM). The aim was to evaluate T-cell function in DCM using different flow cytometry based detection techniques. Following stimulation, the frequency of IFN-gamma-producing CD4+ T cells was significantly lower in patients compared with controls. In contrast, the frequency of IL-4 producing CD4+ T cells was no different. In supernatants of cultured PBMC, IFN-gamma and IL-10 were significantly lower in patients. In addition, lymphocyte proliferation was significantly lower in patients compared with controls, whereas major lymphocyte subsets were not different. IFN-gamma and IL-10 are key cytokines in the ability to mount protective immune responses and to maintain self-tolerance. A reduced activation of T-helper 1 (IFN-gamma producing) cells and a decreased capacity to produce IL-10, found in the present study, could explain parts of the autoimmune features seen in patients with DCM.
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| 2. |
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| 3. |
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| 4. |
- Lindberg, Erika, 1979
(författare)
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T cell Function in Patients with Dilated Cardiomyopathy
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by dilatation of one or both ventricles together with decreased systolic function. Its etiology is still largely unknown. However, immunological alterations such as the presence of autoantibodies, elevated cytokines in plasma, and viral genomes in the myocardium have been frequently reported. The aim of this thesis was to examine T cell function in patients with DCM. First, cytokines in plasma were measured. In accordance with previous reports, plasma cytokines of TNF-alfa, IL-6, IL-10, and CRP were significantly elevated in patients with heart failure. Incorporating an etiology of DCM or ischemic heart disease together with clinical variables in a multivariate analysis, a diagnosis of DCM was found to be independently associated with lower IL-10 levels. Next, specific CD4+ T cell response, accumulated cytokines in supernatant, and lymphocyte proliferation were measured using flow cytometry-based methods following culture of isolated peripheral blood mononuclear cells, and stimulation with Staphylococcus enterotoxin B or phytohaemagglutinin. The frequency of IFN-gamma-producing CD4+ (Th1) cells was significantly lower in patients than in healthy controls. In contrast, no difference was found in the number of IL-4-producing CD4+ (Th2) cells. In addition, IL-10 production in the supernatant and lymphocyte proliferation were both significantly lower in patients. To conclude, these impairments of IFN-gamma and IL-10 are both consistent with an increased susceptibility to chronic infections and autoimmunity. Finally, we investigated the frequency of a single nucleotide polymorphism in the IFN-gamma gene, which alter the transcription level. We found a significant association between the IFN-gamma polymorphism and susceptibility to DCM. This previously unreported finding could be the first diagnostic marker of a DCM of autoimmune etiology. In its entirety, this thesis supports the concept that DCM is a late sequela of myocarditis leading to a disease of autoimmune character.
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| 5. |
- Nowrouzian, Forough, 1957, et al.
(författare)
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Adhesin and superantigen genes and the capacity of Staphylococcus aureus to colonize the infantile gut.
- 2011
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 204:5, s. 714-21
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a pathogen and a skin commensal that is today also common in the infant gut flora. We examine the role of S. aureus virulence factors for gut colonization. S. aureus isolated from quantitative stool cultures of 49 Swedish infants followed from birth to 12 months of age were assessed for 30 virulence-associated genes, spa type, and agr allele by serial polymerase chain reaction (PCR) assays. Strains carrying genes encoding collagen-binding protein, and the superantigens S. aureus enterotoxin O/M (SEO/SEM) had higher stool counts than strains lacking these genes, whereas genes for S. aureus enterotoxin A (SEA) were associated with low counts. A cluster of strains belonging to agr allele I and the spa clonal cluster 630 (spa-CC 630) that carried genes encoding SEO/SEM, SEC, collagen-binding protein, and elastin-binding protein were all long-time colonizers. Thus, certain S. aureus virulence factors might promote gut colonization.
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| 6. |
- Scharin Täng, Margareta, 1962, et al.
(författare)
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Cardiac reserve in the transplanted heart: effect of a graft polymorphism in the beta1-adrenoceptor
- 2007
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 26:9, s. 915-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polymorphism of the beta1-adrenoceptor (beta1-AR) affects outcome and beta-blocker efficacy in patients with heart failure. We studied the influence of the beta1-AR Ser49Gly polymorphism on cardiac reserve in transplanted hearts. METHODS: Beta1-AR polymorphism was determined by allelic discrimination analysis. Patients were divided into two groups: either homozygous for Ser49 (n = 15) or with Gly49 in one or both alleles (Gly49; n = 5). Patients underwent a maximal bicycle exercise test and echocardiographic evaluation at rest and during low-dose dobutamine stress. RESULTS: Patients with Gly49 grafts had better physical endurance (144 +/- 26 vs 112 +/- 31 W, p = 0.03), a trend toward better chronotropic reserve (deltaHR 64 +/- 13 vs 47 +/- 16 bpm, p = 0.056) during exercise, and lower resting heart rate (82 +/- 7 vs 90 +/- 7 bpm, p = 0.04) than those homozygous for Ser49. There were no significant differences in left ventricular ejection fraction (LVEF), with the exception of a decrease in cardiac reserve in patients with the Gly49 variants at the lowest dose of dobutamine (deltaLVEF -4.4 +/- 1.5 vs 2.2 +/- 5.8%, p = 0.04). Doppler myocardial tissue velocities of early relaxation were increased in patients with the Gly49 variants compared with patients homozygous for Ser49, both at rest (14.5 +/- 3.2 vs 10.4 +/- 2.0 cm/s, p = 0.03) and during the lowest dose of dobutamine (15.0 +/- 3.7 vs 10.9 +/- 2.5 cm/s, p = 0.04). CONCLUSIONS: Heart transplant patients with the beta1-AR Gly49 variants had a lower heart rate, and better stress endurance and diastolic function compared with patients homozygous for Ser49. They also showed a trend toward better chronotropic reserve. These results provide a possible explanation for differences in cardiac reserve among patients with heart transplants.
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| 7. |
- Scott, Mark G H, et al.
(författare)
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Cooperative regulation of extracellular signal-regulated kinase activation and cell shape change by filamin A and beta-arrestins.
- 2006
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Ingår i: Molecular and cellular biology. - 0270-7306. ; 26:9, s. 3432-45
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Tidskriftsartikel (refereegranskat)abstract
- beta-Arrestins (betaarr) are multifunctional adaptor proteins that can act as scaffolds for G protein-coupled receptor activation of mitogen-activated protein kinases (MAPK). Here, we identify the actin-binding and scaffolding protein filamin A (FLNA) as a betaarr-binding partner using Son of sevenless recruitment system screening, a classical yeast two-hybrid system, coimmunoprecipitation analyses, and direct binding in vitro. In FLNA, the betaarr-binding site involves tandem repeat 22 in the carboxyl terminus. betaarr binds FLNA through both its N- and C-terminal domains, indicating the presence of multiple binding sites. We demonstrate that betaarr and FLNA act cooperatively to activate the MAPK extracellular signal-regulated kinase (ERK) downstream of activated muscarinic M1 (M1MR) and angiotensin II type 1a (AT1AR) receptors and provide experimental evidence indicating that this phenomenon is due to the facilitation of betaarr-ERK2 complex formation by FLNA. In Hep2 cells, stimulation of M1MR or AT1AR results in the colocalization of receptor, betaarr, FLNA, and active ERK in membrane ruffles. Reduction of endogenous levels of betaarr or FLNA and a catalytically inactive dominant negative MEK1, which prevents ERK activation, inhibit membrane ruffle formation, indicating the functional requirement for betaarr, FLNA, and active ERK in this process. Our results indicate that betaarr and FLNA cooperate to regulate ERK activation and actin cytoskeleton reorganization.
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| 8. |
- Tillander, Jonatan, 1975, et al.
(författare)
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Treatment of periprosthetic joint infections guided by minimum biofilm eradication concentration (MBEC) in addition to minimum inhibitory concentration (MIC): protocol for a prospective randomised clinical trial.
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Prosthetic joint infections (PJIs) are disastrous complications for patients and costly for healthcare organisations. They may promote bacterial resistance due to the extensive antibiotic use necessary in the PJI treatment. The PJI incidence is estimated to be 1%-3%, but the absolute numbers worldwide are high and increasing as large joint arthroplasties are performed by the millions each year. Current treatment algorithms, based on implant preserving surgery or full revision followed by a semitailored antibiotic regimen for no less than 2-3 months, lead to infection resolution in approximately 60% and 90%, respectively. Antibiotic choice is currently guided by minimum inhibitory concentrations (MICs) of free-living bacteria and not of bacteria in biofilm growth mode. Biofilm assays with relatively rapid output for the determination of minimum biofilm eradication concentrations (MBECs) have previously been developed but their clinical usefulness have not been established.This single-blinded, two-arm randomised study of hip or knee staphylococcal PJI will evaluate 6-week standard of care (MIC guided), or an alternative antibiotic regimen according to an MBEC-guided-based decision algorithm. Sixty-four patients with a first-time PJI treated according to the debridement, antibiotics, and implant retention principle will be enrolled at a single tertiary orthopaedic centre (Sahlgrenska University Hospital). Patients will receive 14 days of standard parenteral antibiotics before entering the comparative study arms. The primary outcome measurement is the proportion of changes in antimicrobial regimen from first-line treatment dependent on randomisation arm. Secondary endpoints are unresolved infection, how microbial properties including biofilm abilities and emerging antimicrobial resistance correlate to infection outcomes, patient reported outcomes and costs with a 12-month follow-up.Approval is received from the Swedish Ethical Review Authority, no 2020-01471 and the Swedish Medical Products Agency, EudraCT, no 2020-003444-80.ClinicalTrials.gov ID: NCT04488458.
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| 9. |
- Wehrli, Patrick M., et al.
(författare)
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Exploring bacterial phenotypic diversity using factorial design and FTIR multivariate fingerprinting
- 2014
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Ingår i: Journal of Chemometrics. - : John Wiley and Sons Ltd. - 0886-9383. ; 28:8, s. 681-686
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Tidskriftsartikel (refereegranskat)abstract
- Transmission Fourier transform infrared (FTIR) spectra were obtained from cultures of Staphylococcus aureus that were grown under sets of various environmental conditions enclosing ranges of potential conditions in wound sites. The primary aim of this study was to determine whether bacterial phenotypic diversity could be characterized by FTIR spectroscopy analyses of cultures of S.aureus grown under variable sets of environmental conditions. Designing experiments with full factorial design has shown to be a powerful way to explore an expectedly large array of phenotypic diversity of S.aureus. Various combinations of environmental conditions caused the bacteria to adapt their phenotype, which was assessed via FTIR spectral fingerprinting. Transmission FTIR spectroscopy was found to be superior to other vibrational spectroscopy techniques for this purpose because of its high sensitivity, reproducibility, and rapidity of analysis. The sample preparation presented was fundamental for reproducible results. Different spectral preprocessing methods were compared in combination with scaling methods to obtain distinguishable phenotypes in principal component analysis (PCA) models. Spectral preprocessing with combined filters, including standard normal variate transformation, Savitzky-Golay smoothing, and use of the first derivative in a PCA model with unit variance scaling, gave the most optimal clustering for the data in this study. Spectra obtained from each treatment group were found to have a unique FTIR profile with good reproducibility, and thus PCA resulted in full separation between all groups on three principal components. In conclusion, transmission FTIR spectroscopy in conjunction with design of experiment, and multivariate analysis are powerful tools to investigate phenotypic diversity of S.aureus. © 2014 John Wiley & Sons, Ltd.
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| 10. |
- Wehrli, Patrick M., et al.
(författare)
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Maximising the potential for bacterial phenotyping using time‐of‐flight secondary ion mass spectrometry with multivariate analysis and Tandem Mass Spectrometry
- 2014
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Ingår i: Surface and Interface Analysis. - : Wiley. - 1096-9918 .- 0142-2421. ; 46:1, s. 173-176
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Tidskriftsartikel (refereegranskat)abstract
- The increasing trend towards bacteria becoming resistant to current antibiotic treatments is of great concern to the healthcare industry with severe potential consequences for society as a whole. In many cases, it is the interaction of the antibacterial agent with the targets within the bacterial envelope of the microorganism that is a critical factor. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is uniquely capable of probing the chemistry in this region. This study aimed at optimising sample preparation and data pre-processing for bacterial analysis with ToF-SIMS and principal components analysis to study small chemical differences related to changes in bacterial phenotype that will help to find new antibiotics and understand how antibiotics are trafficked in the bacteria. ToF-SIMS analysis was performed using a J105 instrument equipped with a 40 kV C60+ ion source. Combination of positive and negative ion mode data enhanced the multivariate model quality regarding classification and aided chemical identification particularly when coupled with tandem mass spectrometry. Copyright © 2014 John Wiley & Sons, Ltd.
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