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Sökning: WFRF:(Ringdahl Ulrika)

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1.
  • Drobin, Kimi, et al. (författare)
  • Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depending on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.
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2.
  • Tegern, Matthias, et al. (författare)
  • Inter-rater and test-retest reliability of movement control tests for the neck, shoulder, thoracic, lumbar, and hip regions in military personnel
  • 2018
  • Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Strategies are needed to mitigate the high rates and related risks of musculoskeletal complaints and injuries (MSCI) in the military aviator community. Previous work on Swedish Armed Forces (SwAF) soldiers have shown that proper screening methods have been successful in reducing early discharge from military training. Research has pointed at the importance of optimal spinal movement control in military aviators. The aim of this work was to investigate the inter-rater and test-retest reliability of a battery of clinical tests for evaluating movement control in the neck, shoulders, thoracic, lumbar, and hip regions in a population of SwAF military personnel. Inter-rater and test-retest reliability of 15 movement control tests were assessed by crude and prevalence-adjusted kappa coefficient. The study included 37 (inter-rater) and 45 (test-retest) SwAF personnel and was performed with two physiotherapists simultaneously observing and rating the movements on the first occasion and repeated with one physiotherapist on the second occasion. For inter-rater reliability, the kappa coefficient ranged from .19 to .95. Seven tests showed substantial to almost perfect agreement (kappa > .60). With the adjusted kappa, three more tests reached the level of substantial agreement. The corresponding values for test-retest reliability ranged from .26 to .65. Substantial agreement was attained for two tests, three with adjusted kappa. The following tests can reliably be used when screening for biomechanically less advantageous movement patters in military aviators: Shoulder flexion, and rotation, Neck flexion in sitting and supine, Neck extension and rotation in sitting, Pelvic tilt, Forward lean and Single and Double knee extension tests. Grading criteria for tests in supine and quadruped positions need to be further elaborated.
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3.
  • Ben Nasr, A, et al. (författare)
  • Streptokinase activates plasminogen bound to human group C and G streptococci through M-like proteins.
  • 1994
  • Ingår i: European Journal of Biochemistry. - : Wiley-Blackwell. - 0014-2956. ; 222:2, s. 267-276
  • Tidskriftsartikel (refereegranskat)abstract
    • An ability to interact with plasminogen or plasmin could provide micro-organisms with a mechanism for invasion. Thus, group A, C and G streptococci secrete streptokinase which binds and activates plasminogen. Some streptococci also express surface structures which bind plasminogen without causing its activation. Plasminogen-binding surface proteins were extracted from one group C and one group G streptococcal isolate. Both proteins were found to bind plasmin, fibrinogen and serum albumin in addition to plasminogen. Gene fragments encoding the streptococcal proteins were amplified by PCR and were subsequently cloned and expressed in Escherichia coli. DNA sequence determination revealed for both genes open reading frames encoding proteins which contained repetitive domains and a carboxyl-terminal unrepeated region that were typical of M and M-like proteins. Though the amino-terminal regions of the group C and G streptococcal proteins demonstrated a rather high overall similarity between themselves, they were not similar to the variable regions of other M-like proteins with one exception: there was a 46% identity between the first 22 amino acids of the group G streptococcal protein and the corresponding sequence of PAM, the plasminogen-binding M-like protein of type M53 group A streptococci. Like the proteins extracted from the streptococci, the recombinant proteins bound plasminogen, fibrinogen and albumin. The three plasma proteins bound to separate sites on the streptococcal M-like proteins. Plasminogen bound by the group C and G streptococcal proteins was readily activated by streptokinase, providing evidence for a functional link between the secreted plasminogen-activator and proteins exposed on the bacterial surface.
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4.
  • Ben Nasr, Abdelhakim, et al. (författare)
  • Streptokinase activates plasminogen bound to human group C and group G streptococci through M-like proteins
  • 1994
  • Ingår i: European Journal of Biochemistry. - : Wiley-Blackwell. - 0014-2956. ; 222:2, s. 76-267
  • Tidskriftsartikel (refereegranskat)abstract
    • An ability to interact with plasminogen or plasmin could provide micro-organisms with a mechanism for invasion. Thus, group A, C and G streptococci secrete streptokinase which binds and activates plasminogen. Some streptococci also express surface structures which bind plasminogen without causing its activation. Plasminogen-binding surface proteins were extracted from one group C and one group G streptococcal isolate. Both proteins were found to bind plasmin, fibrinogen and serum albumin in addition to plasminogen. Gene fragments encoding the streptococcal proteins were amplified by PCR and were subsequently cloned and expressed in Escherichia coli. DNA sequence determination revealed for both genes open reading frames encoding proteins which contained repetitive domains and a carboxyl-terminal unrepeated region that were typical of M and M-like proteins. Though the amino-terminal regions of the group C and G streptococcal proteins demonstrated a rather high overall similarity between themselves, they were not similar to the variable regions of other M-like proteins with one exception: there was a 46% identity between the first 22 amino acids of the group G streptococcal protein and the corresponding sequence of PAM, the plasminogen-binding M-like protein of type M53 group A streptococci. Like the proteins extracted from the streptococci, the recombinant proteins bound plasminogen, fibrinogen and albumin. The three plasma proteins bound to separate sites on the streptococcal M-like proteins. Plasminogen bound by the group C and G streptococcal proteins was readily activated by streptokinase, providing evidence for a functional link between the secreted plasminogen-activator and proteins exposed on the bacterial surface.
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5.
  • Gerdtsson, Anna Sandström, et al. (författare)
  • Plasma protein profiling in a stage defined pancreatic cancer cohort – Implications for early diagnosis
  • 2016
  • Ingår i: Molecular Oncology. - : Elsevier. - 1574-7891. ; 10:8, s. 1305-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. Patients with stage I/II PDAC could be discriminated from NC with high accuracy based on a plasma protein signature, indicating a possibility for early diagnosis and increased detection rate of surgically resectable tumors.
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6.
  • Ghatnekar, Ola, et al. (författare)
  • Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature.
  • 2013
  • Ingår i: International Journal of Cancer. - : John Wiley and Sons. - 0020-7136. ; 133:10, s. 2392-2397
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully evaluated concerning effectiveness and healthcare costs. We have developed a framework for modelling cost and health effects from early detection of PC, which for the first time allowed us to analyse its cost-effectiveness. A probabilistic cohort model for estimating costs and quality adjusted life-years (QALY) arising from screening for PC, compared to a "wait-and-see"-approach, was designed. The test accuracy, Swedish survival and costs by tumour stage, expected life gain from early detection and pre-test probabilities in risk-groups, were retrieved from previous investigations. In a cohort of newly diagnosed diabetic patient (incidence 0.71%) the incremental cost per QALY gained (ICER) was €13,500, which is considered cost-effective in Europe. Results were mainly sensitive to the incidence with the ICER ranging from €315 to €204,000 (familial PC 35% and general population 0.046%, respectively). This is the first study focusing on clinical implementation of advanced testing and what is required for novel technologies in cancer care to be cost-effective. The model clearly demonstrated the potential of multiplexed proteomic-testing of PC and also identified the requirements for test accuracy. Consequently, it can serve as a model for assessing the possibilities to introduce advanced test platforms also for other cancer indications. © 2013 Wiley Periodicals, Inc.
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7.
  • Khil, J, et al. (författare)
  • Plasminogen enhances virulence of group A streptococci by streptokinase-dependent and streptokinase-independent mechanisms
  • 2003
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 1537-6613. ; 188:4, s. 497-505
  • Tidskriftsartikel (refereegranskat)abstract
    • Interactions between host plasminogen (Plg) and streptokinase (SK) secreted by group A streptococci ( GAS) have been hypothesized to promote bacterial invasion of tissues. The virulence of GAS strain UMAA2616, after being subcutaneously inoculated into mice, was studied. Skin lesions and mortality were observed after inoculation of 7 x 10(6) cfu. Coadministration of human Plg with UMAA2616 markedly increased virulence. SK-deficient UMAA2616 (UMAA2616-SK-) was generated. Mean skin-lesion area and mortality, after bacterial inoculation (3 x 10(5) cfu), were significantly greater with UMAA2616 in the presence of human Plg than with UMAA2616-SK- in the presence of human Plg (P = .0001). Human Plg also enhanced UMAA2616-SK- vir ulence. Exogenous human Plg enhanced the virulence of MGAS166, a human clinical isolate. These findings suggest that SK-Plg interactions are an important determinant of GAS invasiveness in vivo and that both SK and host Plg activators appear to promote virulence of GAS by catalyzing plasmin formation.
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8.
  • McArthur, Jason D, et al. (författare)
  • Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation.
  • 2008
  • Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : The Federation of American Societies for Experimental Biology. - 1530-6860. ; 22:9, s. 3146-3153
  • Tidskriftsartikel (refereegranskat)abstract
    • A common mammalian defense mechanism employed to prevent systemic dissemination of invasive bacteria involves occlusion of local microvasculature and encapsulation of bacteria within fibrin networks. Acquisition of plasmin activity at the bacterial cell surface circumvents this defense mechanism, allowing invasive disease initiation. To facilitate this process, S. pyogenes secretes streptokinase, a plasminogen-activating protein. Streptokinase polymorphism exhibited by S. pyogenes isolates is well characterized. However, the functional differences displayed by these variants and the biological significance of this variation has not been elucidated. Phylogenetic analysis of ska sequences from 28 S. pyogenes isolates revealed 2 main sequence clusters (clusters 1 and 2). All strains secreted streptokinase, as determined by Western blotting, and were capable of acquiring cell surface plasmin activity after incubation in human plasma. Whereas culture supernatants from strains containing cluster 1 ska alleles also displayed soluble plasminogen activation activity, supernatants from strains containing cluster 2 ska alleles did not. Furthermore, plasminogen activation activity in culture supernatants from strains containing cluster 2 ska alleles could only be detected when plasminogen was prebound with fibrinogen. This study indicates that variant streptokinase proteins secreted by S. pyogenes isolates display differing plasminogen activation characteristics and may therefore play distinct roles in disease pathogenesis.-McArthur, J. D., McKay, F. C., Ramachandran, V., Shyam, P., Cork, A. J., Sanderson-Smith, M. L., Cole, J. N., Ringdahl, U., Sjöbring, U., Ranson, M., Walker, M. J. Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation.
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9.
  • Ringdahl, Ulrika, et al. (författare)
  • A role for the fibrinogen-binding regions of streptococcal M proteins in phagocytosis resistance
  • 2000
  • Ingår i: Molecular Microbiology. - : Wiley-Blackwell. - 1365-2958. ; 37:6, s. 1318-1326
  • Tidskriftsartikel (refereegranskat)abstract
    • All virulent group A streptococcal isolates bind fibrinogen, a property that is closely linked to expression of type-specific antiphagocytic surface molecules designated M proteins. Here we show that although the M proteins from two different strains, M1 and M5, both bind fibrinogen with high affinity, they interact with different regions in the ligand. Moreover, mapping experiments demonstrated that the fibrinogen-binding regions in the M1 and M5 proteins are quite dissimilar at the amino acid sequence level and that they bind to different regions in the plasma protein. In spite of these differences, the fibrinogen-binding regions of M1 and M5 could both be shown to contribute to streptococcal survival in human blood, providing evidence for the distinct function of a plasma protein interaction in bacterial pathogenesis.
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10.
  • Ringdahl, Ulrika, et al. (författare)
  • Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes.
  • 1998
  • Ingår i: Journal of Biological Chemistry. - : ASBMB. - 1083-351X. ; 273:11, s. 6424-6430
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial surface-associated plasmin formation is believed to contribute to invasion, although the underlying molecular mechanisms are poorly understood. To define the components necessary for plasmin generation on group A streptococci we used strain AP53 which exposes an M-like protein ("PAM") that contains a plasminogen-binding sequence with two 13-amino acid residues long tandem repeats (a1 and a2). Utilizing an Escherichia coli-streptococcal shuttle vector, we replaced a 29-residue long sequence segment of Arp4, an M-like protein that does not bind plasminogen, with a single (a1) or the combined a1a2 repeats of PAM. When expressed in E. coli, the purified chimeric Arp/PAM proteins both bound plasminogen, as well as plasmin, and when used to transform group A streptococcal strains lacking the plasminogen-binding ability, transformants with the Arp/PAM constructs efficiently bound plasminogen. Moreover, when grown in the presence of plasminogen, both Arp/PAM- and PAM-expressing streptococci acquired surface-bound plasmin. In contrast, plasminogen activation failed to occur on PAM- and Arp/PAM-expressing streptococci carrying an inactivated streptokinase gene: this block was overcome by exogenous streptokinase. Together, these results provide evidence for an unusual co-operation between a surface-bound protein, PAM, and a secreted protein, streptokinase, resulting in bacterial acquisition of a host protease that is likely to spur parasite invasion of host tissues.
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