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1.
  • Munthe, Christian, 1962 (författare)
  • Etiska aspekter på regenerativ medicin : Ethical aspects on regenerative medicine
  • 2003
  • Ingår i: SNIB-konferensen 2003, Chalmers tekniska högskola, Göteborg, 16-18 maj 2003.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Inom den regenerativa medicinen strävar man efter att ersätta skadat eller sjukligt biologiskt mänskligt material (celler, organ, kroppsdelar) med nya biologiska komponenter. Området aktualiserar en rad etiska frågeställningar vad gäller (1) produktionen av ersättningsmaterialet (t.ex. embryonala stamceller eller införskaffande av transplantationsvävnad från donatorer), (2) risker i samband med försök på människa (genmodifierat material, material från djur), samt (3) gränserna för hur långt man bör gå i denna slags försök att förlänga människans livsspann. Föredraget ger en kort översikt över dessa frågeställningar, ståndpunkter och argument i debatten kring dem.
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  • Asberg, Marie, et al. (författare)
  • Novel biochemical markers of psychosocial stress in women.
  • 2009
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.
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7.
  • Ludvigsson, Jonas F., et al. (författare)
  • Celiac disease and risk of subsequent type 1 diabetes : a general population cohort study of children and adolescents
  • 2006
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 29:11, s. 2483-2488
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort.RESEARCH DESIGN AND METHODS:We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses.RESULTS:Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P < 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P < 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001).CONCLUSIONS:Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive.
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8.
  • Pulkkinen, Hertta, et al. (författare)
  • Recombinant human type II collagen as a material for cartilage tissue engineering.
  • 2008
  • Ingår i: International Journal of Artificial Organs. - : Wichtig Editore Srl. - 0391-3988 .- 1724-6040. ; 31:11, s. 960-969
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro.METHODS: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks. The gels were investigated with confocal microscopy, histology, and biochemical assays.RESULTS: Confocal microscopy revealed that the cells maintained their viability during the entire cultivation period. The chondrocytes were evenly distributed inside the gels, and the number of cells and the amount of the extracellular matrix increased during cultivation. The chondrocytes maintained their round phenotype during the 4-week cultivation period. The glycosaminoglycan levels of the tissue increased during the experiment. The relative levels of aggrecan and type II collagen mRNA measured with realtime polymerase chain reaction (PCR) showed an increase at 1 week.CONCLUSION: Our results imply that recombinant human type II collagen is a promising biomaterial for cartilage tissue engineering, allowing homogeneous distribution in the gel and biosynthesis of extracellular matrix components.
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9.
  • Petersson, Göran, 1941 (författare)
  • ANTIOXIDANTER mot aggressiva syreradikaler
  • 2006
  • Ingår i: Tidningen Cancer- och Allergifonden informerar, 2006. ; , s. 5-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Som komplement till det enzymatiska försvaret mot syreradikaler har kostens antioxidanter en huvudroll. De senaste åren har efterhand hundratals antioxidanter inom grupperna karotenoider och flavonoider identifierats. Artikeln visar hur vårt behov av viktiga ämnen från dessa grupper kan täckas via bra kostval.
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10.
  • Mamontov, Eugen, 1955, et al. (författare)
  • The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
  • 2006
  • Ingår i: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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11.
  • Olsen, Birgitta, et al. (författare)
  • A view of the Neisseria gonorrhoeae population in Sweden in 2005 : phenotypic and genetic characterisation
  • 2006
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • AimsTo phenotypically and genotypically characterise clinical N. gonorrhoeae isolates transmitted in Sweden during 2005 and to compare with characteristics of N. gonorrhoeae populations in other countries.IntroductionIn Sweden, the gonorrhoea incidence decreased from the beginning of the 1970s to 1996. From 1997 the incidence has almost annually increased, mainly due to a rise in domestic cases of young heterosexuals of both sexes and homosexual men. Furthermore, during recent decades resistance to most of the traditional antibiotics used in the treatment of gonorrhoea has rapidly increased worldwide. Availability of effective diagnostics, treatment and surveillance of epidemiological characteristics (antibiotic susceptibility, serovars and genotypes) are main tools for control of the transmission of infection.Materials, Methods & ResultsN. gonorrhoeae isolates (n=175) cultured in Sweden in 2005 and received at the Swedish Reference Laboratory for Pathogenic Neisseria were included. Phenotypic characterisation was performed by antibiotic susceptibility testing and serovar determination using both Genetic systems (GS) and Pharmacia (Ph) panels of monoclonal antibodies (MAbs). Genetic characterisation was performed using N. gonorrhoeae multiantigen sequence typing (NG-MAST) that analyses more variable segments of the porB gene (490 bp) and of the tbpB gene (390 bp).All isolates were susceptible to cefixime, ceftriaxone, and spectinomycin. The levels of intermediate susceptibility and resistance to azithromycin, ciprofloxacin, and ampicillin were 2.3%, 49.7% and 75.3%, respectively (Table 1). Fifty-seven (33%) of the isolates were -lactamase producing.In total, 33 of the isolates were determined as serogroup WI (PorB1a). These were assigned nine different GS-serovars and seven different Ph-serovars. Two of the PorB1a isolates were not serotypeable using Ph MAbs. The remaining 142 isolates were determined as serogroup WII/III (PorB1b). These isolates were assigned 18 different GS-serovars and 38 different Ph-serovars.The isolates displayed 66 and 56 divergent NG-MAST porB and tbpB alleles, respectively. These resulted in assignment of 95 different sequence types (STs), of which 34 have not been previously described. ST40 (n=15), ST225 (n=12), ST1813 (n=9), ST5 (n=8), ST753 (n=6), ST323 (n=5), and ST211 (n=4), were the most prevalent STs. Four STs were represented by three isolates, 20 STs by two isolates and 64 STs by single isolates (Figure 1).ConclusionsA highly diverse N. gonorrhoeae population was transmitted in Sweden during 2005, which can reflect importation of strains from abroad, and/or in some geographic areas suboptimal diagnostics and incomplete epidemiological surveillance. However, many clusters of isolates, which can reflect the existence of several transmission chains, were also identified.Serovar determination is still fairly effective, rapid, inexpensive, easily performed and remains a valuable primary epidemiological marker of N. gonorrhoeae, which can supplement the superior genetic characterisation.
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14.
  • Buendia, Ruben, 1982, et al. (författare)
  • A Novel Approach for Removing the Hook Effect Artefact from Electrical Bioimpedance Spectroscopy Measurements
  • 2009
  • Ingår i: Journal of Physics: Conference Series. - : Institute of Physics Publishing Ltd.. - 1742-6596.
  • Konferensbidrag (refereegranskat)abstract
    • Very often in Electrical Bioimpedance (EBI) spectroscopy measurements the presence of stray capacitances creates a measurement artefact commonly known as Hook Effect. Such an artefact creates a hook-alike deviation of the EBI data noticeable when representing the measurement on the impedance plane. Such Hook Effect is noticeable at high frequencies but it also causes a data deviation at lower measurement frequencies. In order to perform any accurate analysis of the EBI spectroscopy data, the influence of the Hook Effect must be removed. An established method to compensate the hook effect is the well known Td compensation, which consist on multiplying the obtained spectrum, Zmeas() by a complex exponential in the form of exp[jTd]. Such a method cannot correct entirely the Hook Effect since the hook-alike deviation occurs a broad frequency range in both magnitude and phase of the measured impedance, and by using a real value for Td. First, a real value only modifies the phase of the measured impedance and second, it can only correct the Hook Effect at a single frequency. In addition, the process to select a value for Td by an iterative process with the aim to obtain the best Cole fitting lacks solid scientific grounds. In this work the Td compensation method is revisited and a modified approach for correcting the Hook Effect that includes a novel method for selecting the correcting values is proposed. The initial validation results confirm that the proposed method entirely corrects the Hook Effect at all frequencies.
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  • Petersson, Göran, 1941 (författare)
  • Oxidativ stress bakom cancer, allergi och åldrande
  • 2008
  • Ingår i: Tidningen Cancer- och Allergifonden informerar, 2008 nr 2. ; , s. 12-13
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Oxidativ stress är en beteckning för bildning och förekomst av främst syreradikaler i kroppen. Dessa reaktiva ämnen skadar arvsmassa, enzymer och andra proteiner, blodfetter och biologiska membraner. De är därför en grundorsak till cancer, allergier, åderförfettning och cellens åldrande.Antioxidanter motverkar bildning av och eliminerar redan bildade syreradikaler. Mindre känt är att bildning av radikaler kan förebyggas och motverkas även på en rad andra sätt.
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19.
  • Krzemieniecki, Krzysztof, et al. (författare)
  • Targeting of solid tumors and blood malignancies by antibody-based therapies - EGFR-pathway as an example
  • 2006
  • Ingår i: Central European Journal of Biology. - : Versita. - 1895-104X .- 1644-3632. ; 1:2, s. 167-182
  • Tidskriftsartikel (refereegranskat)abstract
    • A well-coordinated interaction between extracellular signals and intracellular response forms the basis of life within multicellular organisms, with growth factors playing a crucial role in these interactions. Discoveries in recent years have shown that components of the Epidermal Growth Factor (EGF) signaling system have frequently been used by cancer cells to autonomously provide survival and proliferation signals. The main focus of this review is the ErbB epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases including ErbB1/EGFR, ErbB2/HER2/neu, ErbB3/HER3, and ErbB4/HER4 as therapeutic targets. Since the ErbB receptor family regulates cell proliferation through the Ras-mitogen-activated protein kinase (RAS/MAPK) pathway, and cell survival and transformation through the phosphatidylinositol 3-kinase (PI3K/AKT) pathway, pharmacological targeting of these pathways is also discussed. We will also address the clinical studies that have been conducted to evaluate antibody-based therapies mostly on solid tumors and hematologic malignancies. (c) Versita Warsaw and Springer-Verlag Berlin Heidelberg. All rights reserved.
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20.
  • Mamontov, Eugen, 1955 (författare)
  • Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
  • 2006
  • Ingår i: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
  • Konferensbidrag (refereegranskat)abstract
    • Advanced generalized-kinetic-theory (GKT) models for biological systems are developed for populations of active (or living) particles [1]-[5]. These particles are described with both the stochastic variables common in kinetic theory (such as time, the particle random location and velocity) and the stochastic variables related to the internal states of an active particle. Evolution of these states represents biological, ecological, or social properties of the particle behavior. Paper [6] analyzes a number of the well-known statistical-mechanics approaches and shows that the active-particle GKT (APGKT) is the only treatment capable of modelling living systems. Work [2] summarizes the significance of the notion of an active particle in kinetic models. This notion draws attention to the features distinguishing living matter from nonliving matter. They are discussed by many authors (e.g., [7]-[15], [1]-[3], [6], [16]-[18]). Work [11] considers a lot of differences between living and nonliving matters, and the limitations of the modelling approaches developed for nonliving matter. Work [6] mainly focuses on the comparison of a few theoretical mechanics treatments in terms of the key living-matter properties formulated in [15]. One of the necessary properties of the evolution of living systems is homeorhesis. It is, loosely speaking, a peculiar qualitative and quantitative insensitivity of a living system to the exogenous signals acting on it. The earlier notion, homeostasis, was introduced by W. B. Cannon in 1926 who discussed the phenomenon in detail later [7]. Homeorhesis introduced by C. H. Waddington [8, p. 32] generalizes homeostasis and is well known in biology [8], [9], [12]. It is an inherent part of mathematical models for oncogeny (e.g., [16]-[18], [6, Appendix]). Homeorhesis is also discussed in [3, Section 4] in connection with APGKT. Homeorhesis is documented in ecology (e.g., [11], [13, the left column on p. 675]) where it is one of the key notions of the strong Gaia theory, a version of the Gaia theory (e.g., [14, Chapter 8]). The strong Gaia theory “states that the planet with its life, a single living system, is regulated in certain aspects by that life” [14, p. 124]. The very origin of the name “Gaia” is related to homeorhesis or homeostasis [14, p. 118]. These notions are also used in psychology and sociology. If evolution of a system is not homeorhetic, the system can not be living. Work [6, Appendix] derives a preliminary mathematical formulation of homeorhesis in terms of the simplest dynamical systems, i.e. ordinary differential equations (ODEs). The present work complements, extended, and further specify the approach of [6, Appendix]. The work comprises the two main parts. The first part develops the sufficient conditions for ODE systems to describe homeorhesis, and suggests a fairly general structure of the ODE model. It regards homeorhesis as piecewise homeostasis. The model can be specified in different ways depending on specific systems and specific purposes of the analysis. An example of the specification is also noted (the PhasTraM nonlinear reaction-diffusion model for hyperplastic oncogeny [16]-[18]). The second part of the work discusses implementation of the above homeorhesis ODE model in terms of a special version [3] of APGKT (see above). The key feature of this version is that the components of a living population need not be discrete: the subdivision into the components is described with a general, continuous-discrete probability distribution (see also [6]). This enables certain properties of living matter noted in [15]. Moreover, the corresponding APGKT model presents a system of, firstly, a generalized kinetic equation for the conditional distribution function conditioned by the internal states of the population and, secondly, Ito's stochastic differential equations for these states. This treatement employs the results on nonstationary invariant diffusion stochastic processes [19]. The second part of the work also stresses that APGKT is substantially more important for the living-matter analysis than in the case of nonliving matter. One of the reasons is certain limitations in experimental sampling of the living-system modes presented with stochastic processes. A few directions for future research are suggested as well. REFERENCES: [1] Bellomo, N., Bellouquid, A. and Delitala, M., 2004, Mathematical topics on the modelling complex multicellular systems and tumor immune cells competition, Math. Models Methods Appl. Sci., 14, 1683-1733. [2] Bellomo, N., 2006, New hot Paper Comments, Essential Science Indicators, http://www.esi-topics.com/nhp/2006 /may- 06-NicolaBellomo.html. [3] Willander, M., Mamontov, E. and Chiragwandi, Z., 2004, Modelling living fluids with the subdivision into the components in terms of probability distributions, Math. Models Methods Appl. Sci. 14, 1495-1520. [4] Bellomo, N. and Maini, P.K., 2005, Preface and the Special Issue “Multiscale Cancer Modelling-A New Frontier in Applied Mathematics”, Math. Models Methods Appl. Sci., 15, iii-viii. [5] De Angelis, E. and Delitala, M., 2006, Modelling complex systems in applied sciences: Methods and tools of the mathematical kinetic theory for active particles. Mathl Comput. Modelling, 43, 1310-1328. [6] Mamontov, E., Psiuk-Maksymowicz, K. and Koptioug, A., 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, Article in Press, 13 pp. [7] Cannon, W.B., 1932, The Wisdom of the Body (New York: Norton). [8] Waddington, C.H., 1957, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (London, George Allen and Unwin). [9] Waddington, C.H., 1968, Towards a theoretical biology, Nature, 218, 525-527. [10] Cotnoir, P.-A., 1981, La compétence environnementale: Une affaire d’adaptation. Séminaire en écologie behaviorale, Univeristé du Québec, Montralé. Available online at: http://pac.cam.org/culture.doc . [11] O’Neill, R.V., DeAngelis, D.L., Waide, J.B. and Allen, T.F.H., 1986, A Hierarchical Concept of Ecosystems, Princeton: Princeton Univ. Press). [12] Sauvant, D., 1992, La modélisation systémique en nutrition, Reprod. Nutr. Dev., 32, 217-230. [13] Christensen, N.L., Bartuska, A.M., Brown, J.H., Carpenter, S., D'Antonio, C., Francis, R., Franklin, J.F., MacMahon, J.A., Noss, R.F., Parsons, D.J., Peterson, C.H., Turner, M.G. and Woodmansee, R.G., 1996, The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management, Ecological Applications, 6, 665-691. Available online at: http://www.esa.org/pao/esaPositions/Papers/ReportOfSBEM.php. [14] Margulis, L., 1998, Symbiotic Planet. A New Look at Evolution (Amherst: Sciencewriters). [15] Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W., 1999, From molecular to modular cell biology, Nature, 402, C47-C52. [16] Mamontov, E., Koptioug, A.V. and Psiuk-Maksymowicz, K., 2006, The minimal, phase-transition model for the cell- number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54, 44 pp., (no. 2, May-June, accepted). [17] Psiuk-Maksymowicz, K. and Mamontov, E., 2005, The time-slices method for rapid solving the Cauchy problem for nonlinear reaction-diffusion equations in the competition of homeorhesis with genotoxically activated hyperplasia, In: European Conference on Mathematical and Theoretical Biology - ECMTB05 (July 18-22, 2005) Book of Abstracts, Vol.1 (Dresden: Center for Information Services and High Performance Computing, Dresden Univ. Technol.), p. 429 (http://www.ecmtb05.org/). [18] Psiuk-Maksymowicz, K. and Mamontov, E., 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiation therapy, submitted. [19] Mamontov, E., 2005, Nonstationary invariant distributions and the hydrodynamic-style generalization of the Kolmogorov-forward/Fokker-Planck equation, Appl. Math. Lett. 18 (9) 976-982.
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21.
  • Sjöde, A., et al. (författare)
  • Enzyme-based control of oxalic acid in the pulp and paper industry
  • 2008
  • Ingår i: Enzyme and microbial technology. - : Elsevier BV. - 0141-0229 .- 1879-0909. ; 43:2, s. 78-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Enzymatically catalyzed decomposition of oxalic acid in bleaching filtrates from the pulp and paper industry offers a possibility to enduringly prevent oxalate scaling problems by specific removal of the oxalic acid in the system rather than by attempting to avoid calcium oxalate precipitation by countermeasures aiming at improved solubility. To achieve a broad evaluation of various oxalate-degrading enzymes and to cover conditions encountered in various types of processes, 16 different bleaching filtrates were collected from pulp mills engaged in mechanical pulping of softwood, mechanical pulping of aspen, and kraft pulping of softwood. A novel oxalate-degrading enzyme provided by Novozymes was compared with commercially available oxalate oxidase from barley and oxalate decarboxylase from Aspergillus niger. The activity of the enzymes in the filtrates was investigated using kinetic analysis and multivariate data analysis. Kinetic analysis indicated that the degradation rates were governed more by inhibitors in the filtrates than by the concentration of oxalic acid. Multivariate data analysis suggested links between high concentrations of certain compounds in the filtrates and high or low enzyme activity, as exemplified by the link between high concentrations of chelators in filtrates from mechanical pulping and low activity of oxalate oxidase from barley. All three enzymes could degrade oxalic acid in all filtrates, despite the fact that very high concentrations of residual hydrogen peroxide were found in several of the filtrates.
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22.
  • Cholujová, Dana, et al. (författare)
  • Comparative study of four fluorescent probes for evaluation of natural killer cell cytotoxicity assays
  • 2008
  • Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 213:8, s. 629-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Cytotoxicity is one of the major defence mechanisms against both virus-infected and tumor cells. Radioactive 51chromium (51Cr) release assay is a “gold standard” for assessment of natural killer (NK) cytolytic activity in vitro. Several disadvantages of this assay led us to design alternative tools based on flow cytometry analysis. Four different fluorescent dyes, calcein acetoxymethyl ester (CAM), carboxyfluorescein succinimidyl ester (CFSE), Vybrant DiO (DiO) and MitoTracker Green (MTG) were tested for labeling of NK target K-562 cells. Target staining stability, spontaneous release of fluorochromes and subsequent accumulation in bystander unstained cells were measured using fluorimetry and flow cytometry. Healthy donor peripheral blood mononuclear cells and affinity column purified NK cells were used as effectors coincubated with target K-562 cells at different E:T ratios for 3h and 90min, respectively. Fluorescent probe 7-amino-actinomycin D was used for live and dead cell discrimination. Bland–Altman statistical method was applied to measure true agreement for all CAM–51Cr, CFSE–51Cr, DiO–51Cr and MTG–51Cr pairs analyzed. Based on the data, none of the four proposed methods can be stated equivalent to the standard 51Cr release assay. Considering linear relationships between data obtained with four fluorochromes and 51Cr release assay as well as linear regression analysis with R2=0.9393 value for CAM–51Cr pair, we found the CAM assay to be the most closely related to the 51Cr assay.
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23.
  • Mahdavi, Jafar, et al. (författare)
  • Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation
  • 2002
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 297:5581, s. 573-578
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.
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24.
  • Regnström, Karin J., 1958-, et al. (författare)
  • Pharmacogenomics in the evaluation of efficacy and adverse events during clinical development of vaccines
  • 2008
  • Ingår i: Pharmacogenomics in Drug Discovery and Development. - Totowa, NJ : Humana Press. - 9781588298874 - 9781597452052 ; , s. 469-479
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • The understanding of vaccine-induced immune responses in adults and infants is limited. Current vaccination schedules for infants are frequently debated. Especially, the relationship among the timing, the frequency of the dosing, and the generation of an immunological memory are debated. Vaccine antigen-induced cytokine responses to vaccinations given in infancy are of particular interest because little is known about cellular responses in this age, and the information available is based on antibody responses. Pharmacogenomics is ideally suited to study cellular responses related to immune response, in addition, toxicity, inflammation, apoptosis, stress, and oncogenesis can be monitored, since the expression of thousands of genes can be measured in a single experiment. © 2008 Humana Press, a part of Springer Science + Business Media, LLC.
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25.
  • Urban, Constantin, et al. (författare)
  • Identification of cell surface determinants in Candida albicans reveals Tsa1p, a protein differentially localized in the cell
  • 2003
  • Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 544:1-3, s. 228-235
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify cell surface proteins of Candida albicans, the predominant fungal pathogen in humans, we have established an approach using a membrane impermeable biotin derivative in combination with affinity purification. We were able to identify 29 different proteins under two distinct conditions. Among mannoproteins, heat shock proteins and glycolytic enzymes we found thiol-specific antioxidant-like protein 1 (Tsa1p) to be differentially localized depending on the conditions applied. Only in hyphally grown cells Tsa1p was localized to the cell surface whereas in blastospores no surface but mainly nuclear localization was found. This indicates that cell surface expression of at least some proteins is mediated by differential translocation.
  •  
26.
  • Stålhammar, Anna, et al. (författare)
  • Policies for labour management - existence and content
  • 2008
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Blackwell Publishing. - 0283-9318 .- 1471-6712. ; 22:2, s. 259-264
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To prevent dystocia, it is important to have criteria for labour onset and policies for diagnosing and treating uterine inertia. Uterine inertia is often followed by complications such as prolonged labour, caesarean section, instrumental labour and a negative birth experience, and prevention and proper treatment are therefore important. The Swedish National Board of Health and Welfare has stipulated that labour wards should have policies for labour management. The aim of this study was to investigate the extent to which labour wards in Sweden have such policies. For those wards with policies for labour management, a further aim was to study the content of the policies. METHODS: A descriptive survey presenting information from 48 of 49 labour wards in Sweden. Descriptive statistics were used. RESULTS: Three of the 48 labour wards had written policies concerning all four main issues of interest. Written policies existed regarding criteria for labour onset at 11 wards, diagnosis of uterine inertia at 13 wards and treatment of uterine inertia at 21 wards. Seventeen wards had written policies for when during the progress of labour neuraxial analgesia was recommended. CONCLUSIONS: The majority of labour wards in Sweden did not have written policies, and there was no consensus among the wards regarding criteria for diagnosing labour onset and uterine inertia, policies for treatment of uterine inertia, or about recommendations for when to use neuraxial analgesia. It is possible that the lack of policies could imply a risk for nonevidence-based labour management.
  •  
27.
  • Mamontov, Eugen, 1955, et al. (författare)
  • Oncogenic hyperplasia caused by combination of various factors: A decision-support software for radionuclide therapy
  • 2007
  • Ingår i: Workshop "Mathematical Modelling and Analysis of Cancer Invasion of Tissues", Mar 26, 2007 - Mar 30, 2007, Dundee, Scotland.
  • Konferensbidrag (refereegranskat)abstract
    • The present work deals with the software based on the PhasTraM model [1] for oncogenic hyperplasia, the first stage of formation of any solid tumor. The work generalizes the related results of [2]-[6] and discusses application of the software for decision support in radionuclide therapy. The software capabilities to allow for combinations of various causes of oncogeny are emphasized. The causes comprise inflammation, immune dysfunction, and chronic psychological stress. The immune dysfunction is represented with hypogammaglobulenimia expressed in terms of the concentration of the immunoglobulin-G molecules. The level of chronic pychological stress is described with the concentration of the interleukin-6 molecules. The work considers how application of the software can support decisions on the specific radionuclide-therapy setting depending on the tissue-, organ-, and patient-specific data. This is illustrated by a number of numerical-simulation results, also the ones which include the effects of common and fractionation-based radionuclide-therapy modalities. A proper attention is paid to how specifically the input data can be prepared by prospective users of the software, i.e. the specialists who apply radionuclide therapy. The work also formulates a few directions for future research in connection with the features of the everyday work of the prospective users. REFERENCES: [1] E. Mamontov, K. Psiuk-Maksymowicz, A. Koptioug, 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, 44(7-8) 595-607. [2] E. Mamontov, A. V. Koptioug, K. Psiuk-Maksymowicz, 2006, The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54(2) 61-101. [3] K. Psiuk-Maksymowicz and E. Mamontov, 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiotherapy, Mathl Comput. Modelling, Special Issue
  •  
28.
  • Kroon, Martin, et al. (författare)
  • Elastic properties of anisotropic vascular membranes examined by inverse analysis
  • 2009
  • Ingår i: Computer Methods in Applied Mechanics and Engineering. - : Elsevier BV. - 0045-7825 .- 1879-2138. ; 198:45-46, s. 3622-3632
  • Tidskriftsartikel (refereegranskat)abstract
    • An inverse method for estimating the distributions of the nonlinear elastic properties of inhomogeneous and anisotropic vascular membranes such as cerebral aneurysms is proposed. The material description of the membrane is based on a versatile structural model able to represent multiple collagen layers and the passive response of the vascular wall. Each individual layer is assumed to behave transversely isotropic following exponential stiffening with increasing loading. The model includes four parameters to be explainable physically: two initial stiffnesses of the collagen fabric, a parameter related to the nonlinearity of the collagen fabric, angle between the principal directions of the collagen fabric and a reference coordinate system. For this finite deformation problem a finite element framework for membranous structures considering pressure boundary loading is outlined. i.e. the principle of virtual work, its linearisation and the related spatial discretisation. The estimation procedure consists of the following three steps: (i) in vivo or in vitro approaches record the mechanical responses of membranous structures whose properties are to be determined; (ii) define a corresponding finite element model; (iii) minimise an error function (regarding the unknown parameters) that quantifies the deviation of the numerical prediction from the recorded data. To achieve a robust parameter estimation, an element partition method is employed. The outcome of the procedure is affected by the number of nodes defined on the membrane surface and the number of load steps. In a numerical example, the proposed procedure is assessed by reestablishing given reference distributions in a reference membrane. The deviations of the estimated material parameter distributions from the related reference fields are within just a few percent. In most of the investigated cases the standard deviation for the resulting maximum principal stress was even below 1%, which is accurate enough for rupture risk assessment of vascular membranes.
  •  
29.
  •  
30.
  • van West, D, et al. (författare)
  • A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression
  • 2004
  • Ingår i: Molecular Psychiatry. - London : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 9:3, s. 287-292
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing amounts of data suggest that affective disorders might be related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the stress-response systems. Arginine vasopressin (AVP) influences several symptoms, relevant to affective disorders, notable memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). Five SNPs were identified in AVPR1b and genotyped in two well-diagnosed samples of patients with recurrent major depression and matched controls. In the Swedish sample, we observed significant allele (P=0.02) and genotype (P=0.01) association with SNP AVPR1b-s3, and in the Belgian sample, a borderline significant association with SNP AVPR1b-s5 (P=0.04). In both patient-control samples, the haplotype defined by alleles A-T-C-A-G for the AVPR1b-s SNPs s1-s2-s3-s4-s5 was significantly over-represented in controls compared to patients. Our data support a protective effect of this major haplotype for recurrent major depression.
  •  
31.
  • Mayans, Sofia, 1976-, et al. (författare)
  • TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden
  • 2007
  • Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 15:3, s. 342-346
  • Tidskriftsartikel (refereegranskat)abstract
    • A recent study found association of one microsatellite and five single nucleotide polymorphisms (SNPs) in intron 3 of the TCF7L2 gene with type 2 diabetes (T2D) in the Icelandic, Danish and American populations. The aim of the present study was to investigate if those SNPs were associated to T2D in two (family- and population-based) cohorts from northern Sweden. We genotyped four of the associated SNPs in a case-control cohort consisting of 872 T2D cases and 857 controls matched with respect to age, sex and geographical origin and in a sample of 59 extended families (148 affected and 83 unaffected individuals). Here, we report replication of association between T2D and three SNPs in the case-control (rs7901695, P=0.003; rs7901346, P=0.00002; and rs12255372, P=0.000004) and two SNPs in the family-based (rs7901695, P=0.01 and rs7901346, P=0.04) samples from northern Sweden. This replication strengthens the evidence for involvement of TCF7L2 in T2D.
  •  
32.
  • Hellerud, Christina, 1955, et al. (författare)
  • Clinical heterogeneity and molecular findings in five Polish patients with glycerol kinase deficiency: investigation of two splice site mutations with computerized splice junction analysis and Xp21 gene-specific mRNA analysis.
  • 2003
  • Ingår i: Molecular genetics and metabolism. - 1096-7192. ; 79:3, s. 149-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Five cases of glycerol kinase deficiency are presented with clinical, biochemical, and genetic results. Two had the glycerol kinase deficiency as part of an Xp21 contiguous gene deletion syndrome-complex form-and three had an isolated form of the enzyme deficiency. In these we found two splice site mutations (IVS1+4A>G, IVS9-1G>T) and one insertion (1393_1394insG). In patients with the complex form, a deletion of the DAX1, GK genes and the distal part of the DMD gene was found. A computerized study was performed to predict the effects of the splice site mutations. It showed that the IVS9-1G>T mutation substantially altered and removed the wild-type site and enhanced a cryptic site seven nucleotides downstream, and that the IVS1+4A>G diminished the strength of the wild-type donor site from strong to leaky. To verify these predictions, we developed an RT-PCR system with gene-specific primers that exclusively amplifies the Xp21 glycerol kinase gene transcript. Identification of individuals at risk is motivated by a need to avoid delay in a correct diagnosis. For reliable identification of heterozygotes for isolated glycerol kinase deficiency, knowledge of the specific mutation in the proband is required. This is easily obtained with the RT-PCR analyses developed in this study.
  •  
33.
  • Berglund, Jonas, et al. (författare)
  • Hotspots of biased nucleotide substitutions in human genes
  • 2009
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:1, s. e26-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (dN/dS) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.
  •  
34.
  • Bolshakova, A.V., et al. (författare)
  • Comparative analysis of subcellular fractionation methods for revealing a-actinin 1 and a-actinin 4 in A431 cells
  • 2009
  • Ingår i: Cell and Tissue Biology. - : SP MAIK Nauka/Interperiodica. - 1990-519X .- 1990-5203. ; 3:2, s. 188-197
  • Tidskriftsartikel (refereegranskat)abstract
    • a-Actinin 1 and a-actinin 4 are actin-binding proteins with shared structural functions that are responsible for the regulation of several processes in the cell. Based on previous data on the different distribution of these proteins in the nucleus and cytoplasm, we have studied in detail the presence of a-actinin 1 and a-actinin 4 in subcellular fractions in the A431 cells spread on fibronectin. The detection of a-actinins in some particular fractions has been shown to depend on the method of lysis, as well as whether the preliminary low-temperature freezing of cells was used. The application of various fractionation methods has allowed us to conclude that a-actinin 4 is present in all cytoplasmic and nuclear subfractions, whereas, in addition to in the cytoplasm, a-actinin 1 can also be revealed in the nuclear envelope fraction.
  •  
35.
  • Borzacchiello, A, et al. (författare)
  • Rheological characterization of vocal folds after injection augmentation in a preliminary animal study
  • 2004
  • Ingår i: Journal of bioactive and compatible polymers (Print). - London : Sage Publications. - 0883-9115 .- 1530-8030. ; 19:4, s. 331-341
  • Tidskriftsartikel (refereegranskat)abstract
    • The investigation of vocal folds viscoelastic properties in an animal model (rabbit) after injection of various augmentation substances, 6 months after injection, is reported. The injected materials were: hyaluronan-based materials (Hylan B gel and Deflux(R)), cross-linked collagen (Zyplast(R)) and polytetrafluoroethylene (Teflon(R)). Rheological properties of the augmentation substances were also evaluated. The results from these animal experiments indicate that the viscoelastic properties of the vocal folds injected with Deflux(R), Zyplast(R) and Hylan B gel are similar to the healthy vocal folds (non-injected samples) used as control, thus demonstrating that these materials are good candidates for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.
  •  
36.
  • Edlund, Bror, et al. (författare)
  • A proposed stoichiometrical calibration procedure to achieve transferability of D-dimer measurements and to characterize the performance of different methods
  • 2006
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 39:2, s. 137-142
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There is little transferability between D-dimer levels obtained by different reagents today. This makes it difficult to compare results from different clinical studies. OBJECTIVES: We give a comprehensive proposal for calibration of D-dimer assays. All crucial steps and underlying assumptions are made explicit. METHODS: The new approach is based on using a set of fibrinolysates of patient samples clotted and treated with tPA to obtain maximal conversion to D-dimers. Their expected maximal D-dimer concentrations are calculated stoichiometrically from their different fibrinogen values and the published molecular masses of fibrinogen and average D-dimer. The characteristics of five latex enhanced D-dimer immunoassays were also tested against early and late fibrin fragments using this procedure. These were produced by prolonged fibrinolysis of a set of patient samples of varying fibrinogen concentrations. RESULTS: These varied typically between methods and lysis times. One of the methods showing the highest yield irrespective of lysis time was used for calibration. A linear standard curve with zero intercept and R2 = 0.95 was obtained. CONCLUSION: Following this procedure will allow better transferability of D-dimer in future clinical trails.
  •  
37.
  • Enroth, Cristofer, et al. (författare)
  • Crystal structure of a protein, structurally related to glycosyltransferases, encoded in the Rhodobacter blasticus atp operon
  • 2008
  • Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - Amsterdam : Elsevier/North Holland. - 1570-9639 .- 1878-1454. ; 1784:2, s. 379-384
  • Tidskriftsartikel (refereegranskat)abstract
    • The F1-ATP synthase atp operon in the proteobacterium Rhodobacter blasticus contains six open reading frames, encoding six hypothetical proteins. Five of these subunits, in the stoichiometry (ab)3gde make up the catalytic F1-ATP synthase complex similarly in bacteria, chloroplasts and mitochondria. The sixth gene of the Rb. blasticus atp operon, urf6, shows very little sequence homology to any protein of known structure or function. The gene has previously been cloned, the product (called majastridin) has been heterologously expressed in Escherichia coli, and purified to high homogeneity (Brosché et al. (1998) Eur. J. Biochem. 255: 87-92). We have solved the X-ray crystal structure and refined a model of majastridin to atomic resolution. Here we present the crystal structures of apo-majastridin and the complex of majastridin with Mn2+ and UDP and show it has extensive structural similarity to glycosyltransferases (EC 2.4). This is the first structure determined from a new group of distantly related bacterial proteins of at least six members. They share the identical amino acids that bind Mn2+and a triplet of amino acids in the putative sugar-binding site.
  •  
38.
  • Hughes, Kate, et al. (författare)
  • Gene expression in transfected cells
  • 2002
  • Ingår i: Calcium-Binding Protein Protocols. - Totowa, NJ : Humana Press. - 9780896036895 ; , s. 355-363
  • Bokkapitel (refereegranskat)abstract
    • A general approach to address the biological function of a calcium-binding protein, or another protein, in living cells is to increase or decrease the activity of the protein in the cell and analyze the effects on cell functions. In many cases, it is desirable to determine the effects of overexpressing the protein or a constitutively active or dominantly negative derivative, or to express the protein in a cell that normally lacks it. This is achieved by introducing its gene exogenously. The cDNA for the protein is cloned downstream of an active promoter in a plasmid designed for expression in mammalian cells. This expression plasmid is then transfected into the cell.
  •  
39.
  •  
40.
  • Oliynyk, Igor, et al. (författare)
  • Azithromycin increases chloride efflux from cystic fibrosis airway epithelial cells
  • 2009
  • Ingår i: Experimental Lung Research. - : Taylor & Francis. - 0190-2148 .- 1521-0499. ; 35:3, s. 210-221
  • Tidskriftsartikel (refereegranskat)abstract
    • It was investigated whether azithromycin (AZM) stimulates chloride (Cl−) efflux from cystic fibrosis (CF) and non-CF airway epithelial cells, possibly secondary to up-regulation of the multidrug resistance protein (MDR). CF and non-CF human airway epithelial cell lines (CFBE and 16HBE) were treated with 0.4, 4, and 40 μ g/mL AZM for 4 days. Cl− efflux was explored in the presence or absence of specific inhibitors of CFTR and alternative Cl−  channels. Six CF patients received AZM (500 mg daily) for 6 months. The percentage of predicted forced vital capacity (FVC%), forced expiratory volume (FEV1%), and the number of acute exacerbations were compared before and after treatment. Nasal biopsies were taken before and after treatment, and mRNA expression of MDR and CFTR was determined by in situ hybridization. A significant dose-dependent increase of Cl− efflux from CFBE cells (but not from 16HBE cells) was observed after AZM treatment. A CFTR inhibitor significantly reduced AZM-stimulated Cl−  efflux from CFBE cells. A significant improvement in FEV1%, and fewer exacerbations were observed. AZM treatment did not affect mRNA expression of MDR and CFTR. The stimulation of Cl− efflux could be part of the explanation for the clinical improvement seen among the patients.
  •  
41.
  • Särndahl, Eva, et al. (författare)
  • Neutrophil activation status in stable coronary artery disease.
  • 2007
  • Ingår i: PLoS ONE. - San Fransisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 2:10, s. e1056-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: During the last years, neutrophils have emerged as important players in atherogenesis. They are highly activated in peripheral blood of patients with unstable angina. Moreover, a primed state of circulating neutrophils has been proposed in patients with stable angina. Our aim was to investigate the neutrophil activation status in patients with stable coronary artery disease (CAD) at conventional drug treatment. Methodology and principal findings: Thirty patients with stable CAD and 30 healthy controls were included using a paired design. The neutrophil expression of CD18 and high-affinity state of CD11b was analysed by flow cytometry before and after stimulation with chemoattractants. Also, the production of reactive oxygen species (ROS) was determined by chemiluminescence. During basal conditions, the neutrophil expression of CD18 or high-affinity state of CD11b did not differ between patients and controls. Chemoattractants (Interleukin-8 and Leukotriene B(4)) did not increase either the expression or the amount of high-affinity CD11b/CD18-integrins in CAD patients compared to controls, and had no effect on the production of ROS. On the other hand, the ROS production in response to C3bi-opsonised yeast particles and the neutrophils' inherent capacity to produce ROS were both significantly decreased in patients. Conclusion/Significance: We could not find any evidence that neutrophils in patients with stable CAD were primed, i.e. more prone to activation, compared to cells from healthy controls. According to our data, the circulating neutrophils in CAD patients rather showed an impaired activation status. It remains to be elucidated whether the neutrophil dysfunction in CAD is mainly a marker of chronic disease, an atherogenic factor or a consequence of the drug treatment.
  •  
42.
  • Turoverova, L.V., et al. (författare)
  • Analysis of extracellular matrix proteins produced by cultured cells
  • 2009
  • Ingår i: Cell and Tissue Biology. - : SP MAIK Nauka/Interperiodica. - 1990-519X .- 1990-5203. ; 3:5, s. 497-502
  • Tidskriftsartikel (refereegranskat)abstract
    • The extracellular matrix (ECM) is a highly organized multimolecular structure essential for the vital functions of any organism. Although much of the data of extracellular matrix components has been accumulated, the isolation of an entire set of these proteins remains a complex procedure due to the high content of fibrillar proteins and proteoglycans, which form multidomain, netlike structures. In the study presented, we developed a method for isolating ECM proteins from cell cultures. Human epidermoid carcinoma cells A431 and fibroblasts obtained from normal and scar human skin were used. We showed that EDTA solution removed cells from culture plates without destroying the cell membranes. Subsequent treatment of remaining ECM proteins with acetic acid in order to dissociate collagen fibers significantly improved the fractioning of ECM proteins. The extraction of remaining proteins from the surface of the culture plate was preformed by a buffer developed based on Laemmli probe buffer. Using this method, we isolated ECM proteins synthesized by cultured cells, and the extracted proteins were suitable for future analysis by SDS PAGE and two-dimentional electrophoresis, as well as for identifying individual proteins by mass spectrometry. This study may allow us to compare assortments of ECM proteins isolated from different sources, and elucidate impact of various proteins on structure and property of extracellular matrix of investigated cells.
  •  
43.
  • Turoverova, L.V., et al. (författare)
  • Analysis of extracellular matrix proteins produced by cultured cells
  • 2009
  • Ingår i: Tsitologiya. - St Petersburg, Russian Federation : Sankt-Peterburgskaya Izdatel'skaya Firma Nauka. - 0041-3771. ; 51:8, s. 691-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular matrix (ECM) is a highly organized multimolecular structure essential for vital function of any organism. Although a lot of data on the extracellular matrix components has been accumulated, an isolation of the entire set of these proteins still remains to be a complex procedure since ECM contains fibrillar proteins and proteoglycans, which form multidomain net-like structures. In the presented study, we developed a method for isolation of ECM proteins from cell cultures. Human epidermoid carcinoma cells A431 and fibroblasts obtained from normal and scar human skin were used. We showed that EDTA solution removed cells from culture plates without destroying the cell membrane. Following treatment of remaining ECM proteins with acetic acid in order to dissociate collagen fibrils significantly improved fractioning of ECM proteins. Extraction of the remained proteins from culture plate surface was preformed using a buffer developed on the basis of Laemmli probe buffer. With this method, we isolated ECM proteins synthesized by culturing cells and suitable for a future analysis by SDS PAGE and two-dimentional electrophoresis as well as for identification of individual proteins by mass-spectrometry. This study may allow comparing protein contents of ECMs isolated from different sources, and elucidate influences of various proteins on the protein and the properties of extracellular matrix of investigated cells.
  •  
44.
  • Winberg Tinnerfelt, Martin, et al. (författare)
  • Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts
  • 2009
  • Ingår i: Microbes and infection. - Paris, France : Elsevier BV. - 1286-4579 .- 1769-714X. ; 11:2, s. 215-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipophosphoglycan (LPG), the major surface glycoconjugate on Leishmania donovani promastigotes, is crucial for the establishment of infection inside macrophages. LPG comprises a polymer of repeating Gal beta 1,4Man alpha-PO4 attached to a lysophosphatidylinositol membrane anchor. LPG is transferred from the parasite to the host macrophage membrane during phagocytosis and induces periphagosomal F-actin accumulation correlating with an inhibition of phagosomal maturation. The biophysical properties of LPG suggest that it may be intercalated into membrane rafts of the host-cell membrane. The aim of this study was to investigate if the effects of LPG on phagosomal maturation are mediated via action on membrane rafts. We show that LPG accumulates in rafts during phagocytosis of L. donovani and that disruption of membrane rafts abolished the effects of LPG on periphagosomal F-actin and phagosomal maturation, indicating that LPG requires intact membrane rafts to manipulate host-cell functions. We conclude that LPG associates with membrane rafts in the host cell and exert its actions on host-cell actin and phagosomal maturation through subversion of raft function.
  •  
45.
  • Winberg Tinnerfelt, Martin, 1976- (författare)
  • Leukocyte responses to pathogens : integrins, membrane rafts and nitric oxide
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • During microbial invasion, leukocytes of the innate immunity are rapidly recruited to the site of infection where they internalize (phagocytose), kill and digest the invaders. To aid this process, leukocytes express surface receptors such as Toll-like receptors, β2-integrins and Fc-receptors. The β2-integrins are also used for attachment to the extracellular matrix and are important for migration. When pro- vs. anti-inflammatory regulation of β2-integrins was investigated, it was found that chemotactic factors modulate neutrophil adhesion through altered affinity and/or avidity of β2-integrins. A bacteria-derived chemoattractant evoked a large increase in affinity as well as in mobility and clustering, while an early, host-derived chemotactic factor induced increased clustering and surface mobility, but only a slight increase in affinity. Anti-inflammatory lipoxin affected β2-integrin avidity, but not affinity.The leukocyte membrane is composed of lipids and proteins, which are inhomogeneously distributed. Specific domains in the membrane, membrane rafts, are enriched in signaling proteins and receptors. It was found that lipophosphoglycan (LPG) a virulence factor and membrane component of the parasite Leishmania donovani, accumulated in macrophage rafts during infection, inhibited PKCα translocation to the membrane and halted phagosomal maturation. Membrane rafts were instrumental for LPG to exert its effect. We further showed that nitric oxide (NO) rescued phagosomal maturation halted by Leishmania donovani parasites, possibly through effects on actin dynamics. NO did not affect parasite virulence per se. Moreover, lipoarabinomannan (LAM), a virulence factor on Mycobacterium tuberculosis (Mtb) bacteria, also inserted itself into macrophage membrane rafts. LAM from a less virulent strain (PILAM) was less efficiently inserted. Insertion could to some extent be inhibited by phosphatidylinositol mannoside (PIM), another structural molecule from Mtb. LAM did not activate the p38 MAPK signaling pathway nor did LAM interfere with TLR 2 or 4 signaling. In neutrophil leukocytes we observed a simultaneous, calciumdependent up-regulation of membrane rafts and secretion of azurophilic granules at the site of phagocytosis. Rafts were also found in the phagosome membrane. Wild type Streptococcus pyogenes bacteria, which can survive phagocytosis, modulated raft delivery.
  •  
46.
  • Horn, Michael (författare)
  • Cardiac MR spectroscopy: a window for studying physiology
  • 2005
  • Ingår i: Magnetic Resonance Imaging: Methods and Biological Applications, series: Methods in Molecular Medicine. - Totowa, NJ : Humana Press Inc.. - 1588293971 ; , s. 224-248
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Cardiac magnetic resonance spectroscopy (MRS) opens a window to the metabolism of the heart. Various intermediates of metabolic pathways can be observed and followed over time. Most applications of cardiac MRS have been performed with the 31P nuclei, which reflect the metabolites from the high-energy phosphate metabolism. Other nuclei, such as 1H or 13C, have also been investigated but less intensively, most likely because of either large background signals (e.g., water) or inherent low sensitivity of the method. MRS can be used for the examination of tissue extracts, isolated organs, whole animals in vivo, as well as healthy human subjects and patients. Although the primary motivation is to gain an understanding of metabolism using animal models, a potential for diagnostic applications in humans certainly exists.
  •  
47.
  • Molina, Daniel Martinez, et al. (författare)
  • Expression and purification of the recombinant membrane protein YidC : A case studyfor increased solubility and stability
  • 2008
  • Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928 .- 1096-0279. ; 62:1, s. 49-52
  • Tidskriftsartikel (refereegranskat)abstract
    • YidC is an inner membrane protein from Escherichia coli and is an essential component in insertion, trans- location and assembly of membrane proteins in the membranes. Previous purification attempts resulted in heavy aggregates and precipitated protein at later stages of purification. Here we present a rapid and straightforward stability screening strategy based on gel filtration chromatography, which requires as little as 10 lg of protein and takes less than 15 min to perform. With this technique, we could rapidly screen several buffers in order to identify an optimum condition that stabilizes purified YidC. After optimization we could obtain several milligrams of purified YidC that could be easily prepared at high con- centrations and that was stable for weeks at +4 C. The isolated protein is thus well suited for structural studies.
  •  
48.
  • Nilsson, Jonas, 1970, et al. (författare)
  • Norwalk virus-like particles bind specifically to A, H and difucosylated Lewis but not to B histo-blood group active glycosphingolipids.
  • 2009
  • Ingår i: Glycoconjugate journal. - : Springer Science and Business Media LLC. - 1573-4986 .- 0282-0080.
  • Tidskriftsartikel (refereegranskat)abstract
    • Noroviruses and norovirus virus-like particles (VLPs) exhibit strain specific patterns in their binding to ABH and Lewis histo-blood group antigens. In this study we demonstrate for the first time specific binding of Norwalk virus VLPs to type 1 and type 2 chain glycosphingolipids (GSLs) carrying ABH and Lewis antigens. N-succinimidyl-3-tributylstannyl benzoate (ATE) was precursor labeled with (125)I and then conjugated to VLPs. The (125)I-VLPs were used in GSL thin-layer chromatogram binding assays and displayed binding to H type 1, Lewis b, A type 1, A Lewis b GSLs but no binding to B type 1 or B Lewis b GSLs. For the type 2 chain GSLs the Norwalk VLPs bound to H type 2, Lewis y, A type 2 and A Lewis y. In addition, the VLPs bound to several complex GSLs from blood group O and A, but not from blood group B red blood cells.
  •  
49.
  • Nyström, Kristina, 1977, et al. (författare)
  • Induction of sialyl-Lex expression by herpes simplex virus type 1 is dependent on viral immediate early RNA-activated transcription of host fucosyltransferase genes. : Induction of sialyl-Lewis x expression by HSV-1
  • 2009
  • Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:8, s. 847-59
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously shown that varicella-zoster virus (VZV) and cytomegalovirus (CMV) infection of diploid human fibroblasts (HEL) results in neo-expression of Lewis antigens sialyl Lewis x (sLe(x)) and Lewis y (Le(y)), respectively, after transcriptional activation of different combinations of dormant human fucosyltransferase genes (FUT1, FUT3, FUT5, and FUT6), whose gene products are responsible for the synthesis of Le antigens. Here, we show that herpes simplex virus type 1 (HSV-1) also induces sLe(x) expression dependent on induction of FUT3, FUT5, and FUT6 transcription in infected cells. HSV-1 induction of FUT5 was subsequently used as a model system for analyzing the mechanism of viral activation of dormant fucosyltransferase genes. We show that this is a rapid process, which gives rise to elevated FUT5 RNA levels already at 90 min postinfection. Augmented FUT5 transcription was found to be dependent on transcription of viral genes, but not dependent on the immediate early proteins ICP0 and ICP4, as demonstrated by experiments with HSV-1 mutants defective in expression of these genes. Augmented FUT5 transcription takes place in cycloheximide-treated HSV-1-infected cells, suggesting a more direct role for IE viral RNA during activation of cellular FUT5.
  •  
50.
  • Ihnatko, Robert, 1972-, et al. (författare)
  • TNF signaling : early events and phosphorylation.
  • 2007
  • Ingår i: General Physiology and Biophysics. - : Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences. - 0231-5882 .- 1338-4325. ; 26:3, s. 159-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumor necrosis factor-alpha (TNF) is a major mediator of apoptosis as well as immunity and inflammation. Inappropriate production of TNF or sustained activation of TNF signaling has been implicated in the pathogenesis of a wide spectrum of human diseases, including cancer, osteoporosis, sepsis, diabetes, and autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TNF binds to two specific receptors, TNF-receptor type I (TNF-R1, CD120a, p55/60) and TNF-receptor type II (TNF-R2, CD120b, p75/80). Signaling through TNF-R1 is extremely complex, leading to both cell death and survival signals. Many findings suggest an important role of phosphorylation of the TNF-R1 by number of protein kinases. Role of TNF-R2 phosphorylation on its signaling properties is understood less than TNF-R1. Other cellular substrates as TRADD adaptor protein, TRAF protein family and RIP kinases are reviewed in relation to TNF receptor-mediated apoptosis or survival pathways and regulation of their actions by phosphorylation.
  •  
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