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Sökning: WFRF:(Wistedt Annika)

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  • 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.
  • Carlsson Wistedt, Annika (författare)
  • Plasminogen and protein PAM: Interactions between streptococcal surface proteins and the human fibrinolytic system
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Pathogenic bacteria often produce potent proteases capable of destroying host tissue thereby providing the bacteria with tools for spreading and nutrient access. This thesis describes how group A, C and G streptococci can acquire surface bound protease activity through an alternative mechanism, namely by binding and activation of the human protease precursor plasminogen. Group A streptococci of certain serotypes (M33, M41, M52, M53 and M56) were found to efficiently bind plasminogen. Similar to a previously described protein (PAM) expressed by a M53 strain, the plasminogen-binding surface proteins of the other four serotypes belonged to the M protein family, known to contain major virulence factors of group A streptococci. In addition, a subset of group C and G streptococci were shown to bind plasminogen through M-like proteins. In binding experiments with recombinantly produced fragments and a synthetic pepide we located the plasminogen-binding site of protein PAM to a 29 amino acid region containing a twice-repeated sequence. Two lysine residues within this sequence appeared to be critical for the interaction with plasminogen. The major binding site for PAM to plasminogen was localised to kringle two of human plasminogen. PAM reacted poorly with plasminogen from some other species, including rheusus plasminogen which only differs from the human form in two positions. PAM-expressing bacteria grown in human plasma acquired surface associated plasmin activiy in spite of the presence of physiological plasmin inhibitors. A chimerical M-like protein, harbouring the plasminogen-binding motif of PAM, transferred this ability to another streptococcal strain. Inactivation of the streptokinase gene abolished surface plasmin acquisition whereas addítion of exogenous streptokinase overcame this block.
  • Johansson, Marcus, et al. (författare)
  • Significant variations in the seroprevalence of C6 ELISA antibodies in a highly endemic area for Lyme borreliosis: evaluation of age, sex and seasonal differences
  • 2017
  • Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY. - 0903-4641 .- 1600-0463. ; 125:5, s. 476-481
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to assess the seroprevalence of C6 ELISA antibodies in healthy blood donors in Kalmar County, Sweden, in relation to age, sex and time of year (peak season vs off season). In addition, we wanted to assess serological status over time in a group of C6 ELISA seropositive blood donors. Sera were collected from 273 (131 women, 142 men) blood donors in autumn 2011 and 300 (144 women, 156 men) in winter 2014. All sera were analysed in the C6 ELISA and the results were interpreted according to the manufacturers instructions. The seroprevalence was 22% (females 16%, males 28%) in 2011 and 24% (females 15%, males 33%) in 2014. The seroprevalence was significantly higher in males and increased with age. The highest seroprevalence was observed among elderly men, 60-70 years old (46% in 2011 and 52% in 2014). No significant difference was detected in seropositivity between the samples collected in winter and autumn. All (34/34) seropositive blood donors followed over time remained seropositive at follow-up after 22-29 months. C6 ELISA seroprevalence in healthy blood donors is high in Kalmar County, thereby reducing the specificity of a positive test result regarding the clinical diagnosis of Lyme borreliosis (LB). Although C6 seroprevalence appears not to be affected by seasonal sample time, it varies greatly with age and sex. A careful evaluation of pre-test probability is therefore of the utmost importance in the clinical diagnosis of LB, especially in elderly men. We suggest that colleagues in other endemic regions also consider initiating similar evaluations to optimize the laboratory and clinical diagnosis of LB in relation to age and sex.
  • Larsson, Marie C., et al. (författare)
  • Rapid identification of pneumococci, enterococci, beta-haemolytic streptococci and S. aureus from positive blood cultures enabling early reports
  • 2014
  • Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334 .- 1471-2334. ; 14:146
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:The aim of this study was to evaluate diagnostic tests in order to introduce a diagnostic strategy to identify the most common gram-positive bacteria (pneumococci, enterococci, β-haemolytic streptococci and S. aureus) found in blood cultures within 6 hours after signalling growth.METHODS:The tube coagulase test was optimized and several latex agglutination tests were compared and evaluated before a validation period of 11 months was performed on consecutive positive blood culture patient samples from Kalmar County Hospital, Sweden.RESULTS:During the validation period 150 (91%) of a total of 166 gram-positive cocci (119 in clusters, 45 in chains or pairs and 2 undefined morphology) were correctly identified as S. aureus, CoNS, Pneumococci, Enterococci or group A streptococci (GAS), group B streptococci (GBS), group G streptococci (GGS) within 6 hours with a minimal increase in work-load and costs. The remaining samples (9%) were correctly identified during the next day. No samples were incorrectly grouped with this diagnostic strategy and no patient came to risk by early reporting.CONCLUSION:A simple strategy gives reliable and cost-effective reporting of >90% of the most common gram-positive cocci within 6 hours after a blood cultures become positive. The high specificity of the tests used makes preliminary reports reliable. The reports can be used to indicate the focus of infection and not the least, support faster administration of proper antimicrobial treatment for patients with serious bacterial infections.
  • Lindqvist, Maria, et al. (författare)
  • Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
  • 2014
  • Annan publikation (övrigt vetenskapligt)abstract
    • Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.
  • Schon, Thomas, et al. (författare)
  • A comparative study of three methods to evaluate an intervention to improve empirical antibiotic therapy for acute bacterial infections in hospitalized patients
  • 2011
  • Ingår i: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES. - : Informa Healthcare. - 0036-5548. ; 43:4, s. 251-257
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In order to limit the use of broad-spectrum antibiotics, standardized empirical therapy against acute bacterial infections has been advocated. Methods: Guidelines for acute bacterial infections recommending increased usage of benzylpenicillin and restricted use of fluoroquinolones and cephalosporins have been implemented in Kalmar County, Sweden. We evaluated this strategy by recording therapy in patients with bacteraemia, antibiotic requisition, and point prevalence surveys prior to this intervention and at 6 and 12 months after. Results: Comparing the methods simultaneously, there was good agreement between them and an overall significant change in antibiotic usage. There was a significant shift from cefuroxime to cefotaxime and a borderline significant increase in the use of benzylpenicillin (p == 0.057). Based on the defined daily dose (DDD), a highly significant decrease in total cefotaxime and cefuroxime usage was observed that was not detected when applying the prescribed daily dose (PDD), which is adapted to local treatment practices. No change was found in mortality in Staphylococcus aureus bacteraemia or the incidence of Clostridium difficile infection. Conclusions: We conclude that the implementation of the new guidelines has resulted in a significant change in antibiotic usage, which could be conveniently monitored by antibiotic requisition if PDD is used in addition to DDD.
  • Tjernberg, Ivar, et al. (författare)
  • C6-peptide serology as diagnostic tool in neuroborreliosis
  • 2008
  • Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : John Wiley & Sons Inc.. - 1600-0463 .- 0903-4641. ; 116:5, s. 393-399
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate the usefulness of borrelia serology (Quick ELISA C6 Borrelia assay kit) as a diagnostic tool in cases of suspected neuroborreliosis. A retrospective patient material consisting of 124 paired serum and cerebrospinal fluid samples with a positive anti-borrelia antibody index (AI) using the IDEIA Lyme Neuroborreliosis test was compared with 124 Al-negative matched control subjects. The patients were divided into four groups based on presence of pleocytosis and age above or below 12 years. The presence of positive C6 serology in AI-positive patients with pleocytosis was 89% (83/93), significantly different (p < 0.01) from in patients without pleocytosis (58%, 18/31). In AI-positive patients aged >= 12 years with pleocytosis, 94% (51/54) had a positive C6 serology. Of AI-positive patients with a symptom duration of more than 30 days, 93% (27/29) were positive by the C6 test. We conclude that the C6 serum test, together with clinical evaluation, is a powerful diagnostic tool in adult (>= 12 years) European patients with suspected neuroborreliosis with a symptom duration of more than 30 days. Patients with suspected neuroborreliosis and positive C6 results should be further investigated by lumbar puncture for definite diagnosis.
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  • Resultat 1-7 av 7

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