| 1. |
- Ljungman, Gustaf, et al.
(författare)
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Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 2007
- 2011
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:5, s. 750-757
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: Two thousand four hundred and eighty-seven children (< 15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p < 0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively.
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| 2. |
- Palmqvist, Niklas, 1974, et al.
(författare)
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Bacterial cell wall-expressed protein A triggers supraclonal B-cell responses upon in vivo infection with Staphylococcus aureus
- 2005
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 7:15, s. 1501-11
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that staphylococcal protein A (SpA) anchored to the cell wall of Staphylococcus aureus acts as a virulence factor in septic arthritis. Apart from the ability of SpA to interact with Fcgamma, it also binds to Fab-regions with immunoglobulin heavy chains encoded by the V(H) clan III gene family. The objective of the present study was to investigate whether in vivo expression of SpA by staphylococci induces V(H)III-dependent supraclonal B-cell responses, and whether such responses may affect the ability of the host to produce anti-staphylococcal antibodies. Upon primary infection of mice, a SpA-expressing staphylococcal strain gave rise to significantly higher serum levels of V(H)III-encoded antibodies specific for SpA devoid of Fcgamma-binding ability (MSpA) than an isogeneic spa deletion mutant strain. The V(H)III-dependence of MSpA-specific antibody responses was affected by the size of the staphylococcal inoculum, and differed for IgM and IgG isotypes. Mice that had recovered from a prior mild infection from a SpA-expressing strain were protected against infection-induced weight loss upon reinfection. Although no lasting MSpA-specific IgG was induced by previous mild infection, these protected mice possessed IgG specific for clumping factor A, a conventional staphylococcal protein antigen. Our findings demonstrate that the expression of a B-cell superantigen during staphylococcal infection causes supraclonal changes to the immune system. Notably, while superantigen-triggered B-cell responses do not favor the development of SpA-specific memory B-cells, such responses do not interfere with the development of antibodies specific for a staphylococcal protein antigen associated with protective immunity.
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| 3. |
- Palmqvist, Niklas, 1974, et al.
(författare)
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Clumping factor A-mediated virulence during Staphylococcus aureus infection is retained despite fibrinogen depletion
- 2004
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Clumping factor A (ClfA), a fibrinogen-binding protein expressed on the Staphylococcus aureus cell surface, has previously been shown to act as a virulence factor in experimental septic arthritis. Although the interaction between ClfA and fibrinogen is assumed to be of importance for the virulence of S. aureus, this has not been demonstrated in any in vivo model of infection. Therefore, the objective of this study was to investigate the contribution of this interaction to ClfA-mediated virulence in murine S. aureus-induced arthritis. Ancrod, a serine protease with thrombin-like activity, was used to induce in vivo depletion of fibrinogen in mice. Ancrod treatment significantly aggravated septic arthritis following inoculation with a ClfA-expressing strain (Newman) compared to control treatment. Also, ancrod treatment tended to enhance the arthritis induced by a clfA mutant strain (DU5876), indicating that fibrinogen depletion exacerbates septic arthritis in a ClfA-independent manner. Most importantly, the ClfA-expressing strain was much more arthritogenic than the isogenic clfA mutant, following inoculation of fibrinogen-depleted mice. This finding indicates that the interaction between ClfA and free fibrinogen is not required for ClfA-mediated functions contributing to S. aureus virulence. It is conceivable that ClfA contributes to the virulence of S. aureus through interactions with other host ligands than fibrinogen.
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| 4. |
- Palmqvist, Niklas, 1974, et al.
(författare)
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Expression of staphylococcal clumping factor A impedes macrophage phagocytosis
- 2004
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 188-95
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Tidskriftsartikel (refereegranskat)abstract
- Clumping factor A (ClfA), a fibrinogen-binding protein linked to the Staphylococcus aureus cell wall, is an important virulence factor in infection models, e.g., of septic arthritis. However, the mechanism(s) by which ClfA contributes to the virulence of the bacterium is unknown. In the present study, the impact of ClfA expression on the phagocytosis of S. aureus by macrophages was investigated using clfA-positive and clfA-negative isogenic strains. Furthermore, the possible contribution of ClfA to the proinflammatory and immunostimulatory activity of S. aureus was studied. Our results indicate that ClfA expression significantly protects S. aureus against macrophage phagocytosis. This protection does not require the presence of intact fibrinogen, a ligand for ClfA. ClfA expression by S. aureus enhanced the proliferative response of spleen cells. On the other hand, a clfA mutant strain caused more release of proinflammatory mediators by macrophages than its clfA-positive parental strain. Both the protection against phagocytosis and the enhanced immunostimulatory activity provided by ClfA expression are likely to contribute to the in vivo virulence of S. aureus.
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| 5. |
- Palmqvist, Niklas, 1974, et al.
(författare)
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Fibronectin-binding proteins and fibrinogen-binding clumping factors play distinct roles in staphylococcal arthritis and systemic inflammation
- 2005
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Ingår i: J Infect Dis. - 0022-1899. ; 191:5, s. 791-8
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a commonly encountered pathogen in humans, and it has the potential to cause destructive and life-threatening conditions, including septic arthritis. The pathogenicity of staphylococci depends on the expression of virulence factors. Among these, staphylococcal cell-surface proteins with tissue-adhesive functions have been suggested to mediate the colonization of host tissues, a crucial step in the establishment of infection. We investigated the relative contribution of the fibronectin-binding proteins (FnBPs) and fibrinogen-binding clumping factors (Clfs) to staphylococcal virulence in an experimental model of septic arthritis. The results show that these 2 sets of proteins play distinctly different roles in the development and progression of septic arthritis. Although Clfs significantly contributed to the arthritogenicity of S. aureus, FnBPs had no effect on the development of arthritis. Conversely, FnBPs played an important role in the induction of systemic inflammation, characterized by interleukin-6 secretion, severe weight loss, and mortality.
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| 6. |
- Palmqvist, Niklas, 1974
(författare)
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The impact of Staphylococcus aureus surface proteins on virulence
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus aureus is an important pathogen in humans with the potential to cause life-threatening invasive infections, including sepsis and septic arthritis. The pathogenicity of S. aureus depends on the expression of a variety of virulence factors. The objective of this thesis was to investigate the role of certain cell wall-anchored proteins of S. aureus in the establishment and progression of murine septic arthritis. Specifically, the virulence contributions of the immunoglobulin-binding staphylococcal protein A (SpA), the fibrinogen-binding clumping factors (Clfs), and the fibronectin-binding proteins (Fnbps) were studied. Also, potential mechanisms by which these proteins could contribute to staphylococcal virulence and host interaction were investigated.Wild-type S. aureus strains and defined gene knock-out mutants, i.e. strains deficient with respect to expression of one or several cell wall-anchored proteins, were compared with respect to their abilities to induce arthritis and systemic inflammation following intravenous inoculation of mice. The role of the interaction between clumping factor A (ClfA) and fibrinogen for staphylococcal virulence was studied by defibrinogenation of mice with ancrod. Also, bacteriological, serological and histological analyses were performed ex vivo. In vitro assays for macrophage phagocytosis, spleen cell proliferation, and pro-inflammatory cytokine/chemokine release were also used.Expression of SpA and the Clfs contributed to the development of septic arthritis, and SpA to systemic inflammation. In contrast, expression of the Fnbps had no impact on arthritis development, but triggered severe systemic inflammation in infected mice, characterized by IL-6 production, weight loss and mortality.SpA expression by S. aureus was shown to trigger supraclonal B-cell responses in vivo and spleen cell proliferation in vitro. Expression of ClfA by S. aureus impeded macrophage phagocytosis in a fibrinogen-independent manner, and contributed to the immunostimulatory property of S. aureus. ClfA-mediated arthritogenicity was retained despite fibrinogen depletion of mice, indicating that ClfA contributes to staphylococcal virulence through as yet unidentified mechanisms.In summary, this thesis identifies SpA, Clfs, and Fnbps as virulence factors of S. aureus. SpA and Clfs are arthritogenic factors, whereas SpA and Fnbps contribute to the induction of systemic inflammation and mortality. These surface proteins should be evaluated as targets for vaccination against S. aureus infections.
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