| 1. |
- Andersson, Niklas, 1970, et al.
(author)
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Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men
- 2009
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 33:5, s. 525-533
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Journal article (peer-reviewed)abstract
- Context: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. Objective: To systematically investigate our hypotheses that single- nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. Subjects: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n = 1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n = 3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. Main Outcome Measure: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). Results: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 30 untranslated region C4T (rs4252041, minor allele frequency 4%) SNP was associated with the primary outcome total fat mass (P = 0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN_2018 T4C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P = 0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P < 0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. Conclusions: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have no previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men. International Journal of Obesity (2009) 33, 525-533; doi: 10.1038/ijo.2009.47; published online 17 March 2009
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| 2. |
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| 3. |
- Blank Savukinas, Ulrika, et al.
(author)
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Smad7 promotes self-renewal of hematopoietic stem cells in vivo.
- 2006
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 108:13, s. 4246-4254
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Journal article (peer-reviewed)abstract
- The Smad-signaling pathway downstream of the transforming growth factor–beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad-signaling cascade in Smad7-overexpressing cells. Taken together, these data reveal an important and previously unappreciated role for the Smad-signaling pathway in the regulation of self-renewal of HSCs in vivo.
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| 4. |
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| 5. |
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| 6. |
- Walsh, Sarah H, et al.
(author)
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Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas
- 2007
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 78:4, s. 283-289
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Journal article (peer-reviewed)abstract
- Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin.
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| 7. |
- Ahldén, Mattias, et al.
(author)
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Knee laxity measurements after anterior cruciate ligament reconstruction, using either bone-patellar-tendon-bone or hamstring tendon autografts, with special emphasis on comparison over time
- 2009
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In: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 1433-7347 .- 0942-2056. ; 17:9, s. 1117-24
-
Journal article (peer-reviewed)abstract
- The aims of the study were to analyse the change in knee laxity over time after anterior cruciate ligament (ACL) reconstruction, using either bone-patellar-tendon-bone (BPTB) or hamstring (HS) tendon autografts, and to compare the knee laxity measurements between the study groups both pre-operatively and on multiple follow-up occasions. Another aim was to compare the radiographic findings in terms of degenerative changes between the study groups. A randomised series of 71 patients, who underwent ACL reconstruction using BPTB or HS tendon autografts and interference screw fixation, were included in the study. Of these patients, 47/71 (66%) attended a clinical examination, including laxity measurements using the KT-1000 arthrometer, pre-operatively and on four post-operative occasions; 6 months, 1 year, 2 years and 7 years after the reconstruction. The BPTB group consisted of 22 patients, while there were 25 patients in the HS group. There were no significant differences in the mean side-to-side knee laxity between the BPTB and the HS group pre-operatively or at the follow-up examinations. There was a tendency towards a reduction in side-to-side knee laxity over time in both groups, measured with the KT-1000 arthrometer. The decrease was significant when analysing the injured and uninjured knee separately (injured side p < 0.001 (BPTB) and p = 0.005 (HS), uninjured side p = 0.008 and p = 0.042, respectively). Forty-four patients (BPTB 21, ST 23) underwent a radiographic assessment at the 7-year follow-up, which revealed no significant differences between the study groups in terms of osteoarthritic findings classified according to the Fairbank and Ahlback rating systems. In overall terms, osteoarthritis was identified in 16% (BPTB 19%; ST 13%; n.s.) according to the Ahlback rating system and 68% (BPTB 67%; ST 70%; n.s.) according to the Fairbank rating system. There were no significant differences in knee laxity measurements between the two study groups pre-operatively or at 7 years. A decrease in knee laxity over time was seen in both groups. There were no significant differences between the BPTB and ST groups in terms of osteoarthritic findings at 7 years.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Bäckström, Mattias, et al.
(author)
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Element (Ag, Cd, Cu, Pb, Sb, Tl and Zn), element ratio and lead isotope profiles in a sediment affected by a mining operation episode during the late 19th century
- 2006
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In: Water, Air and Soil Pollution. - : Springer Science and Business Media LLC. - 0049-6979 .- 1573-2932. ; 177:1-4, s. 285-311
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Journal article (peer-reviewed)abstract
- Mining operations at Maarsaetter in 1877-81 resulted in increased metal loading to a small lake, notably as sulphidic tailings. The event is taken as an opportunity to study the present environmental impact of a historical single major metal release. Lake water and four sediment cores were sampled and analysed for principal and trace elements in solid and aqueous phases as well as general hydrochemical conditions. Chronologies were determined from super(206)Pb/ super(207)Pb ratios and historical records.Ordinary sedimentation after the event has lead to that the tailings are found as a distinct layer at a depth of 18-22 cm in the sediment. The layer is characterized by elevated metal concentrations in the solid and pore water phases, respectively, circum neutral pH and sulphate concentrations below detection. Geochemical modelling indicated a preference for carbonate equilibrium in the waste while sulphides prevailed above it. It is concluded that the growth of the ordinary sediment on top of the waste has lead to a physicochemical barrier that seals of the waste from the overlying sediment. Chemical or physical rupture of the barrier will release the metals to downstream regions.According to the chronologies at least three sources have contributed to the present elevated levels of metals, in additions to the release of tailings. Copper from a historical blast furnace prior to the event at Maarsaetter, transport from mineralized parts of the watershed and release of contaminated water from present mining operations maintain elevated levels of notably zinc, silver, cadmium and lead. At present less than 10% of the lead content at the sediment/water interface comes from atmospheric deposition. Increased levels of antimony and thallium were not observed prior to ca 1950.
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| 12. |
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| 13. |
- Casper, C, et al.
(author)
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Coreceptor usage of primary HIV type 1 isolates obtained from different lymph node subsets
- 2005
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In: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 21:12, s. 1003-1010
-
Journal article (peer-reviewed)abstract
- Biological characteristics of virus quantitatively rescued from different cell types present in lymph nodes of HIV-1-infected individuals in various stages of their disease were determined, not including patients with AIDS defining illness. Viruses were obtained by cocultivation with donor monocyte-derived macrophages and T-lymphocytes and their biological phenotype compared to viruses obtained from the peripheral blood mononuclear cells of the same patient. The biological phenotype was determined on established cell lines (U937-2, CEM, and MT-2) and on the U87.CD4 coreceptor indicator cell lines and variable region 3 (V3) of the envelope was subjected to direct sequencing. All isolates obtained from lymph node subsets used CCR5 as coreceptor. Furthermore, these viruses were also sensitive to inhibition by beta-chemokines as analyzed for viruses of one patient. All 12 V3 regions showed a unique sequence indicating compartmentalization within each patient. The biological phenotype of CCR5-dependent (R5) HIV-1 isolates obtained from PBMC resembles the phenotype of viruses isolated from different lymph node cell subsets.
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| 14. |
- Curbo, Sophie, et al.
(author)
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Regulation of interleukin-4 signaling by extracellular reduction of intramolecular disulfides
- 2009
-
In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 390:4, s. 1272-1277
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Journal article (peer-reviewed)abstract
- Interleukin-4 (IL-4) contains three structurally important intramolecular disulfides that are required for the bioactivity of the cytokine. We show that the cell surface of HeLa cells and endotoxin-activated monocytes can reduce IL-4 intramolecular disulfides in the extracellular space and inhibit binding of IL-4 to the IL-4R alpha receptor. IL-4 disulfides were in vitro reduced by thioredoxin 1 (Trx1) and protein disulfide isomerase (PDI). Reduction of IL-4 disulfides by the cell surface of HeLa cells was inhibited by auranofin, an inhibitor of thioredoxin reductase that is an electron donor to both Trx1 and PDI. Both Trx1 and PDI have been shown to be located at the cell surface and our data suggests that these enzymes are involved in catalyzing reduction of IL-4 disulfides. The pro-drug N-acetylcysteine (NAC) that promotes T-helper type 1 responses was also shown to mediate the reduction of IL-4 disulfides. Our data provides evidence for a novel redox dependent pathway for regulation of cytokine activity by extracellular reduction of intramolecular disulfides at the cell surface by members of the thioredoxin enzyme family.
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| 15. |
- Davidson, M., et al.
(author)
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Fluid mixing in growing microscale vesicles conjugated by surfactant nanotubes
- 2005
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 127:4, s. 1251-1257
-
Journal article (peer-reviewed)abstract
- This work addresses novel means for controlled mixing and reaction initiation in biomimetic confined compartments having volume elements in the range of 10-12 to 10-15 L. The method is based on mixing fluids using a two-site injection scheme into growing surfactant vesicles. A solid-state injection needle is inserted into a micrometer-sized vesicle (radius 5-25 μm), and by pulling on the needle, we create a nanoscale surfactant channel connecting injection needle and the vesicle. Injection of a solvent A from the needle into the nanotube results in the formation of a growing daughter vesicle at the tip of the needle in which mixing takes place. The growth of the daughter vesicle requires a flow of surfactants in the nanotube that generates a flow of solvent B inside the nanotube which is counterdirectional to the pressure-injected solvent. The volume ratio ψ between solvent A and B inside the mixing vesicle was analyzed and found to depend only on geometrical quantities. The majority of fluid injected to the growing daughter vesicle comes from the pressure-based injection, and for a micrometer-sized vesicle it dominates. For the formation of one daughter vesicle (conjugated with a 100-nm radius tube) expanded from 1 to 200 μm in radius, the mixing ratios cover almost 3 orders of magnitude. We show that the system can be expanded to linear strings of nanotube-conjugated vesicles that display exponential dilution. Mixing ratios spanning 6 orders of magnitude were obtained in strings of three nanotube-conjugated micrometer-sized daughter vesicles.
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| 16. |
- Egesten, Arne, et al.
(author)
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SpeB of Streptococcus pyogenes differentially modulates antibacterial and receptor activating properties of human chemokines.
- 2009
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:3
-
Journal article (peer-reviewed)abstract
- BACKGROUND: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes. METHODOLOGY/PRINCIPAL FINDINGS: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. CONCLUSIONS/SIGNIFICANCE: SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium.
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| 17. |
- Eriksson, Anna-Lena, 1971, et al.
(author)
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Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men.
- 2009
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:3, s. 1033-41
-
Journal article (peer-reviewed)abstract
- CONTEXT: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids. OBJECTIVE: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men. DESIGN: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 +/- 0.6 yr). Replications of significant associations were performed in the Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 +/- 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 +/- 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry. RESULTS: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1, to be most significantly associated with serum E2 levels (P = 2 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). CONCLUSIONS: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
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| 18. |
- Eriksson, Anna-Lena, 1971, et al.
(author)
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The COMT val158met polymorphism is associated with prevalent fractures in Swedish men.
- 2008
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
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| 19. |
- Forsell, Mattias N E, et al.
(author)
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Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus.
- 2005
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In: Journal of Virology. - 0022-538X .- 1098-5514. ; 79:17, s. 10902-14
-
Journal article (peer-reviewed)abstract
- The current lack of envelope glycoprotein immunogens that elicit broadly neutralizing antibody responses remains a major challenge for human immunodeficiency virus type 1 (HIV-1) vaccine development. However, the recent design and construction of stable soluble gp140 trimers have shown that some neutralization breadth can be achieved by using immunogens that better mimic the functional viral spike complex. The use of genetic delivery systems to drive the in vivo expression of such immunogens for the stimulation of neutralizing antibodies against HIV-1 may offer advantages by maintaining the quaternary structure of the trimeric envelope glycoproteins. Here, we describe the biochemical and immunogenic properties of soluble HIV-1 envelope glycoprotein trimers expressed by recombinant Semliki Forest virus (rSFV). The results presented here demonstrate that rSFV supports the expression of stable soluble gp140 trimers that retain recognition by conformationally sensitive antibodies. Further, we show that rSFV particle immunizations efficiently primed immune responses as measured after a single boost with purified trimeric gp140 protein, resulting in a Th1-biased antibody response. This differed from the Th2-biased antibody response obtained after repeated immunizations with purified gp140 protein trimers. Despite this difference, both regimens stimulated neutralizing antibody responses of similar potency. This suggests that rSFV may be a useful component of a viral vector prime-protein boost regimen aimed at stimulating both cell-mediated immune responses and neutralizing antibodies against HIV-1.
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| 20. |
- Fredriksson, Mattias, et al.
(author)
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An objective comparison of pre-processing methods for enhancement of liquid chromatography-mass spectrometry data
- 2007
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In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1172:2, s. 135-150
-
Journal article (peer-reviewed)abstract
- Four data pre-processing methods have been applied with different settings to data sets obtained from the analysis of a pharmaceutical drug and its degradation products by liquid chromatography�mass spectrometry (LC�MS). The methods compared were the frequently used component detection algorithm (CODA) and three kinds of digital filters�matched filtration (MF), Gaussian second derivative (GSD) and Savitzky�Golay. The aim was to evaluate the performance and robustness of these methods for extracted ion chromatogram (XIC), total ion chromatogram (TIC) and base peak chromatogram (BPC) in the presence of different types of noise. In accordance with theory, the best improvements in signal-to-noise ratio (S/N) of the XICs were obtained with MF under the ideal case with random white noise. However, when highly coloured noise was present, it was found that no improvements in XIC S/N could be obtained with any of the pre-processing methods studied. GSD and CODA did, however, improve the S/N for both TIC and BPC. GSD and CODA also significantly reduced the background in the spectral domain, thereby facilitating the interpretation of the mass spectra. Another advantage associated with CODA and to some extent also with GSD is their data reduction ability.
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| 21. |
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| 22. |
- Grundberg, E, et al.
(author)
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Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
- 2007
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:6, s. 829-837
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Journal article (peer-reviewed)abstract
- Summary Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. Introduction The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. Methods The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. Results When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. Conclusions Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.
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| 23. |
- Hellström, Mats, et al.
(author)
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Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 445:7129, s. 776-80
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Journal article (peer-reviewed)abstract
- In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. VEGF-A is also essential for the induction of endothelial tip cells, but it is not known how single tip cells are selected to lead each vessel sprout, and how tip-cell numbers are determined. Here we present evidence that delta-like 4 (Dll4)-Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina. We show that inhibition of Notch signalling using gamma-secretase inhibitors, genetic inactivation of one allele of the endothelial Notch ligand Dll4, or endothelial-specific genetic deletion of Notch1, all promote increased numbers of tip cells. Conversely, activation of Notch by a soluble jagged1 peptide leads to fewer tip cells and vessel branches. Dll4 and reporters of Notch signalling are distributed in a mosaic pattern among endothelial cells of actively sprouting retinal vessels. At this location, Notch1-deleted endothelial cells preferentially assume tip-cell characteristics. Together, our results suggest that Dll4-Notch1 signalling between the endothelial cells within the angiogenic sprout serves to restrict tip-cell formation in response to VEGF, thereby establishing the adequate ratio between tip and stalk cells required for correct sprouting and branching patterns. This model offers an explanation for the dose-dependency and haploinsufficiency of the Dll4 gene, and indicates that modulators of Dll4 or Notch signalling, such as gamma-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
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| 24. |
- Kaderi, Mohd Arifin, et al.
(author)
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The GNAS1 T393C polymorphism and lack of clinical prognostic value in chronic lymphocytic leukemia
- 2008
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In: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 32:6, s. 984-987
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Journal article (peer-reviewed)abstract
- Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease with no known single predisposing genetic factor shown in all cases. Recently, a single nucleotide polymorphism (SNP) T393C in the GNAS1 gene has been reported to have a clinical impact on CLL progression and overall survival. In order to further investigate the T393C SNP in CLL, we have genotyped 279 CLL cases and correlated the genotypes to clinical outcome and other known prognostic factors such as the immunoglobulin heavy chain variable (IGHV) gene mutation status and CD38 expression. In the present study, no difference in overall survival or time to treatment was observed in the CLL patients with the different genotypes in contrast to the previous report. Furthermore, no correlation was observed with the T393C genotypes and IGHV mutational status, Binet stage or CD38 in this cohort. In summary, our data does not support the use of the T393C GNAS SNP as a clinical prognostic factor in CLL.
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| 25. |
- Kadi, Fawzi, et al.
(author)
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Strength, muscular endurance and EMG characteristics of thigh adductors
- 2006
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In: Isokinetics and exercise science. - 0959-3020 .- 1878-5913. ; 14:3, s. 235-239
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Journal article (peer-reviewed)abstract
- The assessment of thigh adductors' strength and endurance and electromyographical (EMG) characteristics has received little attention compared to other muscle groups. The aim of this study was to investigate strength, endurance performance and EMG characteristics of m. adductor longus and m. gracilis during concentric thigh adduction in soccer and bandy players. Muscular endurance was evaluated using the torque reduction during 70 repeated maximum concentric adductions at an angular velocity of 60°/s. The EMG mean frequency (MNF) and the signal amplitude ratio (SAR, index for muscles' ability to relax between contractions) were analysed. Peak torque decreased significantly throughout the test and no significant differences were found between the two groups. In both muscles, MNF decreased significantly throughout the test. There were no significant differences in MNF and in SAR variables between soccer and bandy players. In conclusion, the present findings reveal a number of significant aspects related to strength and electromyography of hip adductors. © 2006 - IOS Press and the authors. All rights reserved.
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| 26. |
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| 27. |
- Kalén, Mattias, et al.
(author)
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Combination of reverse and chemical genetic screens reveals angiogenesis inhibitors and targets.
- 2009
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In: Chemistry & biology. - : Elsevier BV. - 1879-1301 .- 1074-5521. ; 16:4, s. 432-41
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Journal article (peer-reviewed)abstract
- We combined reverse and chemical genetics to identify targets and compounds modulating blood vessel development. Through transcript profiling in mice, we identified 150 potentially druggable microvessel-enriched gene products. Orthologs of 50 of these were knocked down in a reverse genetic screen in zebrafish, demonstrating that 16 were necessary for developmental angiogenesis. In parallel, 1280 pharmacologically active compounds were screened in a human cell-based assay, identifying 28 compounds selectively inhibiting endothelial sprouting. Several links were revealed between the results of the reverse and chemical genetic screens, including the serine/threonine (S/T) phosphatases ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our results suggest that the combination of reverse and chemical genetic screens, in vertebrates, is an efficient strategy for the identification of drug targets and compounds that modulate complex biological systems, such as angiogenesis.
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| 28. |
- Karlsson, Christofer, et al.
(author)
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SufA - a bacterial enzyme that cleaves fibrinogen and blocks fibrin network formation.
- 2009
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In: Microbiology. - : Microbiology Society. - 1465-2080 .- 1350-0872. ; 155:Pt 1, s. 238-248
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Journal article (peer-reviewed)abstract
- Finegoldia magna is a member of the normal human bacterial flora on the skin and other non-sterile body surfaces, but this anaerobic coccus is also an important opportunistic pathogen. SufA was the first F. magna proteinase to be isolated and characterized. Many bacterial pathogens interfere with different steps of blood coagulation, and here we describe how purified SufA efficiently and specifically cleaves fibrinogen in human plasma. SufA is both secreted by F. magna and associated with the bacterial surface. Successful gene targeting has previously not been performed in anaerobic cocci, but in order to study the role of the SufA that is present at the bacterial surface, we constructed an F. magna mutant that expresses a truncated SufA lacking proteolytic activity. In contrast to wild-type bacteria that delayed the coagulation of human plasma, mutant bacteria had no such effect. Wild-type and mutant bacteria adhered to keratinocytes equally well, but in a plasma environment only wild-type bacteria blocked the formation of fibrin networks surrounding adherent bacteria. The effective cleavage of fibrinogen by SufA suggests that the interference with fibrin network formation represents an adaptive mechanism of F. magna with potential implications also for pathogenicity.
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| 29. |
- Karlsson, Christofer, et al.
(author)
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SufA--a novel subtilisin-like serine proteinase of Finegoldia magna.
- 2007
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In: Microbiology. - : Microbiology Society. - 1465-2080 .- 1350-0872. ; 153:Pt 12, s. 4208-4218
-
Journal article (peer-reviewed)abstract
- Finegoldia magna is an anaerobic Gram-positive bacterium and commensal, which is also associated with clinically important conditions such as skin and soft tissue infections. This study describes a novel subtilisin-like extracellular serine proteinase of F. magna, denoted SufA (subtilase of Finegoldia magna), which is believed to be the first subtilase described among Gram-positive anaerobic cocci. SufA is associated with the bacterial cell surface, but is also released in substantial amounts during bacterial growth. Papain was used to release SufA from the surface of F. magna and the enzyme was purified by ion-exchange chromatography and gel filtration. A protein band on SDS-PAGE corresponding to the dominating proteolytic activity on gelatin zymography was analysed by MS/MS. Based on the peptide sequences obtained, the sufA gene was sequenced. The gene comprises 3466 bp corresponding to a preprotein of 127 kDa. Like other members of the subtilase family, SufA contains the catalytic triad of aspartic acid, histidine and serine with surrounding conserved residues. A SufA homologue was identified in 33 of 34 investigated isolates of F. magna, as revealed by PCR and immunoprinting. The enzyme forms dimers, which are more proteolytically active than the monomeric protein. SufA was found to efficiently cleave and inactivate the antibacterial peptide LL-37 and the CXC chemokine MIG/CXCL9, indicating that the enzyme promotes F. magna survival and colonization.
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| 30. |
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| 31. |
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| 32. |
- Karlsson, Mattias, et al.
(author)
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Lactobacillus rhamnosus GR-1 augments NF-κB and TNF in Escherichia coli-challenged human epithelium
- 2008
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Conference paper (other academic/artistic)abstract
- Epithelial cells are often first responders to microbial invasion, resulting in release of inflammatory mediators such as cytokines and chemokines and subsequent recruitment of immune cells. Several strains from the genus Lactobacillus have been attributed probiotic properties and some of them have been shown to be able to modulate the immune response in vitro and in vivo. L. rhamnosus GR-1, a known probiotic strain was allowed to co-culture with an uroepithelial cell line challenged with heat-killed pathogenic E. coli, resulting in a synergistic up-regulation of the transcription factor NF-κB and increased release of the pro-inflammatory cytokine TNF. Although this L. rhamnosus strain was a poor inducer of uroepithelial NF-κB alone compared to heat-killed E. coli, together with this pathogenic stimulus, it efficiently elicited an epithelial immune response. This effect was greatly reduced if using non-viable lactobacilli suggesting secretion of the active substance. Secreted proteins were isolated and partially mimicked the effect found with viable lactobacilli. Potentiation of the host immune response towards pathogenic E. coli at an early stage using lactobacilli products could facilitate the removal of undesired microbes by activation of the NFκB transcription factor and consequently, epithelial immunity.
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| 33. |
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| 34. |
- Karlsson, Stefan, 1957-, et al.
(author)
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Abatement of ARD with solid alkaline waste materials : A meso-scale field test with emphasis on general hydrochemical parameters
- 2009
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In: Securing the Future and 8<sup>th</sup> ICARD. ; , s. 10 pages-
-
Conference paper (peer-reviewed)abstract
- Abatement of acid mine drainage (ARD) can be made by controlling pH and Eh of the effluents, to optimise retention of major and trace components. The use of solid alkaline waste products from lime production, pulp and paper industry and steel production as well as ashes from bio fuels was evaluated in a meso-scaleexperiment. Each test system hadthree 0.4 m3barrelsthat contained the alkaline waste, a passive support and peat nuggets, in this order.The alkaline wastes consisted of lime kiln dust (LKD), green liquor dreg (GLD), lime mud (LM), LD-slag and fresh and aged ashes. The ARD came either from reactors with acid waste or water taken from a nearby mine shaft. Neutralization was observed for fresh ash, LKD, LD and LM/ash with pH of 6.5, 8.9, 5.3 and 6.6, respectively. The corresponding alkalinities were 0.3, 10.1, 1.8 and 0.5 meqv/l. For carbonated ash and GLD the pH was 3.9 and 4.7 and with acidity remaining. In the best performing systems the average trace metal retention was Pb (>99%), Cu (>99%), Cd (90%) and Zn (70%).
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| 35. |
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| 36. |
- Karlsson, Stefan, et al.
(author)
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Historical pollution of seldom monitored trace elements in Sweden - Part A : sediment properties and chronological indicators
- 2006
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In: Journal of Environmental Monitoring. - 1464-0325 .- 1464-0333. ; 8:7, s. 721-731
-
Journal article (peer-reviewed)abstract
- Sediment cores from four small oligotrophic boreal lakes, with minor acidification, in remote regions of central Sweden were used for historical interpretation of their metal content, with focus on Cu, Cd, Pb and Zn in Lake Stensjön, which has the longest sediment record (at least two centuries according to 210Pb dating). Comparison is made with the other three lakes. Major and trace elements in lake water, porewater and the acid-leached (HNO3) solid sediment phase was analysed with ICP-MS. In addition, general lake water chemistry, TOC and principal anions were measured in the aqueous phases. Redistribution processes were interpreted from geochemical modelling. The solid/solution distribution of pe/pH sensitive elements, indicates a minor diagenetic redistribution and the concentration profiles are therefore suitable for chronological evaluation. The ratios of Al, Ti, Sc and V, indicated a qualitative shift of sedimenting material a century ago, which did not have any impact on the retention of trace elements. Lead had a concentration profile, supported by the 206Pb/207Pb ratio, where it was possible to distinguish preindustrial conditions, early industrialisation in Europe, industrialisation in Sweden, and the use of leaded petrol after the Second World War. Cadmium showed a similar concentration pattern. The zinc profile resembled that of cadmium, but with less enrichment. Local lithogenic sources are believed to be quantitatively important. The solid/solution distribution (Kd) was independent of depth for all four elements. The sediment concentrations of copper and zinc are not related to early industrialisation but its concentration has doubled since the Second World War.
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| 37. |
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| 38. |
- Larsson, Andreas, et al.
(author)
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Design for versatility : the changing face of workspaces for collaborative design
- 2005
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In: Proceedings ICED 05, the 15th International Conference on Engineering Design. - Melbourne : The Institution of Engineers, Australia. - 9780858257887
-
Conference paper (peer-reviewed)abstract
- In a fiercely competitive business climate, which is increasingly characterized by global alliances, partnerships and outsourcing agreements, companies struggle to decrease the negative impact of geographic distance on development efforts. The role of workspaces for collaborative design is gaining considerable attention, and there is currently an increasing interest in moving from individual tools or technologies to a more inclusive view of collaborative workspaces. This paper reports on the underlying motivation and justification for a new collaborative design studio at Luleå University of Technology, Sweden. The studio provides a rapid-response environment, in which the significance of issues raised through ethnographic observations of engineering work can be evaluated and solutions offered.
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| 39. |
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| 40. |
- Lidén, Mattias, 1973, et al.
(author)
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The course of the patellar tendon after reharvesting its central third for ACL revision surgery: a long-term clinical and radiographic study
- 2006
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In: Knee Surg Sports Traumatol Arthrosc. - 0942-2056. ; 14:11, s. 1130-8
-
Journal article (peer-reviewed)abstract
- The choice of the optimal graft for anterior cruciate ligament (ACL) revision surgery is still controversial. Reharvesting the patellar tendon has been suggested as one graft alternative. Our hypothesis was that in the long-term, ACL revision surgery using reharvested patellar tendon autografts would render a good clinical outcome and a normal patellar tendon at the donor site as seen on magnetic resonance imaging (MRI). Fourteen consecutive patients (five women, nine men), who underwent ACL revision surgery using reharvested ipsilateral patellar tendon grafts, were included in the study. They underwent bilateral MRI evaluations of the patellar tendon and were tested for clinical outcome 26 (20-35) and 115 months (102-127) after the revision procedure. On the second occasion, they also underwent standard weight-bearing X-ray examinations.The serial MRI evaluations revealed that the thickness of the patellar tendon at the donor site was significantly increased compared with the non-harvested, normal contralateral side and that the donor-site gap was still visible after 10 years. No significant differences were seen between the 2- and 10-year MRI evaluations. Standard weight-bearing X-ray examinations revealed signs of mild degenerative changes in all patients. Clinical results in terms of the Lysholm score, IKDC evaluation system, one-leg-hop test, KT-1000 laxity test and the knee-walking test revealed no significant differences between the 2- and 10-year assessments. In overall terms, the clinical results were considered to be poor on both occasions. The patellar tendon at the donor site had not normalised 10 years after the reharvesting procedure, as seen on MRI. Furthermore, the clinical results were poor after ACL revision surgery using reharvested patellar tendon autograft.
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| 41. |
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| 42. |
- Magnusson, Mattias, et al.
(author)
-
HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development
- 2007
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 109:9, s. 3687-3696
-
Journal article (peer-reviewed)abstract
- The Homeobox (Hox) transcription factors are important regulators of normal and malignant hematopoiesis because they control proliferation, differentiation, and self-renewal of hematopoietic cells at different levels of the hematopoietic hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13 days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10 was dependent on the HOXA10 concentration, because high levels of HOXA10 had no effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid and megakaryocyte development, demonstrating that tight regulation of HOXA10 is critical for normal development of the erythroid and megakaryocytic lineages. The HOXA10-mediated effects on hematopoietic cells were associated with altered expression of genes that govern stem-cell self-renewal and lineage commitment (eg, hepatic leukemia factor [HlF], Dickkopf-1 [Dkk-1], growth factor independent-1 [Gfi-1], and Gata-1). Interestingly, binding sites for HOXA10 were found in HLF, Dkk-1, and Gata-1, and Dkk-1 and Gfi-1 were transcriptionally activated by HOXA10. These findings reveal novel molecular pathways that act downstream of HOXA10 and identify HOXA10 as a master regulator of postnatal hematopoietic development.
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| 43. |
- Magnusson, Mattias, et al.
(author)
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Hoxa9/hoxb3/hoxb4 compound null mice display severe hematopoietic defects
- 2007
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In: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 35:9, s. 1421-1428
-
Journal article (peer-reviewed)abstract
- Obyective. Members of the box family of homeodomain-containing transcription factors, including hoxa9, hoxb3, and hoxb4 play an important role in the regulation of differentiation, proliferation and self-renewal of hematopoietic stem and progenitor cells. Lack-of-function studies using hoxa9, hoxb4, or hoxb3/hoxb4 null mice demonstrate that all these mutations compromise the repopulating ability of hematopoietic stem cells (HSC), implying similar functions of each of these genes in hematopoiesis. Because cross regulation and cooperativity are known features of box proteins, we investigated mice with a compound deficiency in hoxa9, hoxb3 and hoxb4 (hoxa9/b3/b4) for evidence of synergy between these genes in hematopoiesis. Materials and Methods. Hoxa9/b3/b4 were generated by mating the hoxb3/boxb4 null mice with the hoxa9 null strain and HSC function was measured by competitive repopulating assay and by immunophenotype using fluorescence-activated cell sorting. Results. Our findings demonstrate that the hoxa9/b3/b4 null mice are smaller in body weight, and display a marked reduction in spleen size and cellularity compared to control mice. The numbers of colony-forming unit (CFU)-granulocyte macrophage and CFU-spleen progenitor colonies were normal but hoxa9/b3/b4 null bone marrow contained increased numbers of immunophenotypic HSC (Lin(-), c-kit(+), Sca-1(+), CD150(+)). However the reconstitution defect in hoxa9 null HSC was not enhanced further in the hoxa9/b3/b4 null HSC. Conclusion. These findings demonstrate overlapping functions of hoxa9, hoxb3, and hoxb4 in hernatopoietic cells, and emphasize an important role for these transcription factors for regulation of HSC proliferation. However, none of these box proteins is absolutely essential for generation or maintenance of all major blood lineages. (c) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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| 44. |
- Mellström, Dan, 1945, et al.
(author)
-
Older men with low serum estradiol and high serum SHBG have an increased risk of fractures.
- 2008
-
In: Journal of bone and mineral research. - 1523-4681. ; 23:10, s. 1552-60
-
Journal article (peer-reviewed)abstract
- Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.
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| 45. |
- Mellström, Dan, 1945, et al.
(author)
-
Older men with low serum estradiol and high serum SHBG have an increased risk of fractures
- 2008
-
In: J Bone Miner Res. - : Wiley. - 1523-4681 .- 0884-0431. ; 23:10, s. 1552-60
-
Journal article (peer-reviewed)abstract
- Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p
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| 46. |
- Nilsson, Martin, 1966, et al.
(author)
-
Competitive physical activity early in life is associated with bone mineral density in elderly Swedish men
- 2008
-
In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:11, s. 1557-1566
-
Journal article (peer-reviewed)abstract
- In this population-based study of 75-year-old men (n = 498), we investigated the association between physical activity (PA) early in life and present bone mineral density (BMD). We demonstrate that a high frequency of competitive sports early in life is associated with BMD at several bone sites, indicating that increases in BMD following PA are preserved longer than previously believed. Introduction Physical activity (PA) increases bone mineral density (BMD) during growth. It is unclear if the positive effects remain at old age. In this study, we aimed to determine if PA early in life was associated with BMD in elderly men. Methods In this population-based study, 498 men, 75.2 +/- .3 (mean +/- SD) years old, were included. BMD was assessed using DXA. Data concerning lifetime PA, including both competitive (CS) and recreational sports (RS), and occupational physical load (OPL), were collected at interview. Results Subjects in the highest frequency group of CS in the early period (10-35 years), had higher BMD at the total body (4.2%, p < 0.01), total hip (7.0%, p < 0.01), trochanter (8.7%, p < 0.01), and lumbar spine (7.9%, p < 0.01), than subjects not involved in CS. A stepwise linear regression model showed that frequency of CS in the early period independently positively predicted present BMD at the total body (beta=0.12, p < 0.01), total hip (beta=0.11, p < 0.01), trochanter (beta=0.12, p < 0.01), and lumbar spine (beta=0.11, p=0.01). Conclusions We demonstrate that PA in CS early in life is associated with BMD in 75-year-old Swedish men, indicating that increases in BMD following PA are preserved longer than previously believed.
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| 47. |
- Onoue, Y., et al.
(author)
-
A giant liposome for single-molecule observation of conformational changes in membrane proteins
- 2009
-
In: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 1879-2642 .- 0005-2736. ; 1788:6, s. 1332-1340
-
Journal article (peer-reviewed)abstract
- We present an experimental system that allows visualization of conformational changes in membrane proteins at the single-molecule level. The target membrane protein is reconstituted in a giant liposome for independent control of the aqueous environments on the two sides of the membrane. For direct observation of conformational changes, an extra-liposomal site(s) of the target protein is bound to a glass surface, and a probe that is easily visible under a microscope, such as a micron-sized plastic bead, is attached to another site on the intra-liposomal side. A conformational change, or an angular motion in the tiny protein molecule, would manifest as a visible motion of the probe. The attachment of the protein on the glass surface also immobilizes the liposome, greatly facilitating its manipulation such as the probe injection. As a model system, we reconstituted ATP synthase (FOF1) in liposomes tens of mu m in size, attached the protein specifically to a glass surface, and demonstrated its ATP-driven rotation in the membrane through the motion of a submicron bead. (c) 2009 Elsevier B.V. All rights reserved.
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| 48. |
- Pettersson, Mattias, et al.
(author)
-
Systematizing medical alerts
- 2008
-
In: EHEALTH BEYOND THE HORIZON - GET IT THERE, ISSN 0926-9630, vol 136. ; , s. 753-758
-
Conference paper (peer-reviewed)abstract
- The current Swedish regulations for medical alerts in health records were designed for paper records. Suggestions for computerized systems are now being investigated. A proposed model using three alert categories, graphically represented using three directions, probably combined with three severity levels is presented here. Up represents hypersensitivities, left/back represents alerting diagnosis and right/forward represents alerting current and planned treatments. A small qualitative user study of the alert classification model and some graphical representations of it was conducted. One main finding is that most respondents found the use of directions intuitive as a means of presenting categories. Context dependency, information overload, and future possibilities for automated alert-gathering are also discussed in the paper.
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| 49. |
- Pihl, Johan, 1975, et al.
(author)
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Microfluidic gradient-generating device for pharmacological profiling
- 2005
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:13, s. 3897-3903
-
Journal article (peer-reviewed)abstract
- We describe an on-chip microfluidic gradient-generating device that generates concentration gradients spanning nearly 5 orders of magnitude starting from a single concentration. The exiting stream of drugs held at different concentrations remains laminar in a recording chamber and can be presented as 24 discrete solutions to a cell-based sensor. The high-performance characteristics of the device are demonstrated by pharmacological screening of voltage-gated K + channels (hERG) and ligand-gated GABAA receptors using scanning-probe patch-clamp measurements. Multiple data point dose-response curves and IC 50 and EC 50 values were rapidly obtained, typically in less than 30 min, through its combined functionality of gradient generation and open-volume laminar flow. The device facilitates rapid pharmacological profiling of ion channel and GPCR effectors and enables the acquisition of large numbers of data points with minute sample consumption and handling. © 2005 American Chemical Society.
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| 50. |
- Repits, Johanna, et al.
(author)
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Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge.
- 2008
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In: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 379:1, s. 125-134
-
Journal article (peer-reviewed)abstract
- To better understand the evolution of the viral envelope glycoproteins (Env) in HIV-1 infected individuals who progress to AIDS maintaining an exclusive CCR5-using (R5) virus population, we cloned and sequenced the env gene of longitudinally obtained primary isolates. A shift in the electrostatic potential towards an increased net positive charge was revealed in gp120 of end-stage viruses. Residues with increased positive charge were primarily localized in the gp120 variable regions, with the exception of the V3 loop. Molecular modeling indicated that the modifications clustered on the gp120 surface. Furthermore, correlations between increased Env net charge and lowered CD4(+) T cell counts, enhanced viral fitness, reduced sensitivity to entry inhibitors and augmented cell attachment were disclosed. In summary, this study suggests that R5 HIV-1 variants with increased gp120 net charge emerge in an opportunistic manner during severe immunodeficiency. Thus, we here propose a new mechanism by which HIV-1 may gain fitness.
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