| 1. |
- Lindh, Ingrid, et al.
(författare)
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Feeding of mice with Arabidopsis thaliana expressing the HIV-1 subtype C p24 antigen gives rise to systemic immune responses
- 2008
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - Oxford : Blackwell. - 0903-4641 .- 1600-0463 .- 0903-465X .- 1600-5503. ; 116:11, s. 985-994
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Tidskriftsartikel (refereegranskat)abstract
- Development of transgenic edible plants, to be used as production, storage and delivery systems for recombinant vaccine antigens, is a promising strategy to obtain cost effective vaccines against infectious diseases, not the least for use in developing countries. Therefore, we used Agrobacterium tumefaciens-mediated gene transfer to introduce the p24 gag gene encoding the nucleocapsid protein from HIV-1 subtype C into the Arabidopsis thaliana plant genome. Eighteen plant lines were confirmed positive for the p24 gene by PCR, four of these lines showed an apparent homozygous phenotype when grown on selective medium and these lines also showed transcription of the p24 gene into its corresponding mRNA. The mRNA in all four cases generated the p24 protein in plants, as verified by western blot analysis. The plants were shown to contain between 0.2 µg and 0.5 µg p24 protein per g of fresh tissue. Analysis of the localisation of the p24 protein showed that stem tissue contained the largest amount of protein, more than twice as much as leaf tissue, whereas no p24 protein was detected in roots. By using Southern blotting, we found that 4, 2-3, 2 and 1 T-DNA insertion events took place in the four lines 1, 2, 7, and 10, respectively. The genetic insertions of line 1 were stable from the T1 to the T4 generation and gave rise to the p24 protein in all cases, as verified by western blotting. In mice fed with fresh transgenic A. thaliana (line 10), anti-gag IgG was obtained in serum after a booster injection with recombinant p37Gag. No immune response was observed after equal booster injection of untreated mice or mice fed with A. thaliana WT plants.
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| 2. |
- Hallander, Hans O., et al.
(författare)
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Should fimbriae be included in pertussis vaccines? Studies on ELISA IgG anti-Fim2/3 antibodies after vaccination and infection
- 2009
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Ingår i: APMIS. - : Wiley-Blackwell. - 0903-465X .- 1600-5503 .- 0903-4641 .- 1600-0463. ; 117:9, s. 660-671
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Tidskriftsartikel (refereegranskat)abstract
- The anti-Fim response and long-term persistence after vaccination and infection may be of importance in understanding population immunity. Longitudinal serum samples (n = 1330) from 542 non-infected children related to a Swedish vaccine trial showed that the post vaccination (DTPa5) antibody decay curve for pertussis ELISA IgG anti-fimbriae2/3 (anti-Fim2/3) was bi-phasic. A slower one followed an initial rapid decay approximately 5-6 months after the third dose at 12 months of age. After 71 months, however, 60% still had concentrations above > or =5 EU/ml, a level that had been shown to correlate with decreased risk of disease. Booster responses after re-vaccination with DTPa5 at 4, 5 and 6 years of age were strong and appeared within 1 week after vaccination, indicating immune memory. Ninety-six young children with verified pertussis infection, for whom we had serum samples both before, during and after the infection, showed a high response if they had been primed with fimbriae (either DTPa5 or DTPwc). In contrast, 76% of infected children not primed with fimbriae (a DTPa2 or DT group) only had concentrations below the minimum level of detection in all samples taken during and after the infection. In two Swedish seroepidemiological surveys, one from 1997 just after reintroduction of universal childhood vaccination against pertussis and one from 2007, the proportion of children 2-3 years with anti-Fim2/3 concentrations <5 EU/ml was similar and above 90%. This reflects that the two- or three-component pertussis vaccines (DTPa2 and DTPa3) that were introduced in Sweden in 1996 do not induce anti-Fim2/3 antibodies. In previous studies it was shown in multivariate analyses that levels of IgG anti-Fim2/3 > or =5 EU/ml reduced short-term risk of pertussis in small children. As the antibody response to Fim2/3 after infection is poor in children who have not been primed earlier in life, inclusion of immunogenic Fim2/3 in future pertussis vaccines should be considered.
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| 3. |
- Stark, Lisa, et al.
(författare)
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Staphylococcus aureus isolates from blood and anterior nares induce similar innate immune responses in endothelial cells
- 2009
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Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463 .- 0903-465X .- 1600-5503. ; 117:11, s. 814-824
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the possibility to distinguish virulent from non-virulent isolates, gene expression in human umbilical vein endothelial cells (HUVEC) induced by invasive and colonizing isolates of Staphylococcus aureus was compared. Gene expression in HUVEC was analyzed by microarray analysis after 4 h of infection with Staphylococcus aureus, isolated from healthy nasal carriers (n = 5) and from blood of septic patients (n = 5), to explore possible differences between the groups of bacteria in interaction with HUVEC. All isolates were spa-typed to disclose strain relatedness. Moreover, the isolates were characterized with DNA microarray to determine the presence of virulence genes and to investigate the potential genes of importance in HUVEC interaction. The expression of 41 genes was up-regulated, and four were down-regulated in HUVEC by all isolates. Most of the up-regulated genes encode cytokines, chemokines, interferon-induced proteins, proteins regulating apoptosis and cell proliferation. There was no difference in the gene expression pattern between HUVEC infected with invasive or colonizing isolates. Furthermore, there was no difference in the presence of bacterial virulence genes between the two groups. In conclusion, our data indicate that S. aureus isolates induce comparable expression patterns in HUVEC, irrespective of invasiveness or presence of virulence genes.
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| 4. |
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| 5. |
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| 6. |
- Kühme, Tobias, et al.
(författare)
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Wound contamination in cardiac surgery
- 2007
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 115:9, s. 1001-1007
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the degree of bacterial contamination in the sternal wound during cardiac surgery and the sternal skin flora after operation in order to increase our understanding of the pathogenesis of sternal wound infections. Design: Prospective study where cultures were taken peri- and postoperatively from sternal wounds and skin. Setting: University Hospital. Patients: 201 cardiac surgery patients. Results: 89% of the patients grew bacteria from the subcutaneous sternal tissue. 98% of the patients showed bacterial growth on the surrounding skin at the end of the operation. We found both commensal and nosocomial bacteria in the sternal wound. These bacteria had different temporal distribution patterns. Coagulase-negative staphylococci (CoNS) and Propionibacterium acnes (PA) were by far the most prevalent bacteria during and after the operation. Furthermore, 41% of patients had more than 10 000 CFU/pad CoNS on the skin. There was no correlation between length of operation and number of bacteria. Men displayed higher bacterial counts than women on the skin. Conclusion: Skin preparation with ethanol/chlorhexidine is unable to suppress the physiological skin flora for the duration of a heart operation. A decrease of CoNS and PA postoperatively can be caused by competitive recolonisation of commensal and nosocomial bacteria.
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| 7. |
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| 8. |
- Burova, LA, et al.
(författare)
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Myocardial tissue damage in rabbits injected with group A streptococci, types M1 and M22. Role of bacterial immunoglobuhn G-binding surface proteins
- 2005
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 113:1, s. 21-30
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Tidskriftsartikel (refereegranskat)abstract
- Acute rheumatic fever (ARF) and acute poststreptococcal glomerulonephritis (APSGN), two important sequelae of streptococcal throat or skin infections, according to current concepts may be elicited by autoimmune mechanisms due to molecular mimicry between group A streptococci (GAS) and human tissue. In the case of APSGN, however, Our experimental data have indicated that GAS immunoglobulin-binding surface proteins (IgG Bps) might be of pathogenic significance by triggering anti-IgG production and immune complex formation leading to renal damage. Thus, rabbits injected with IEG-binding, as opposed to non-binding, GAS strains were found to develop renal deposition of IgG and complement factor C3 and inflammatory and degenerative glomerular changes resembling the picture seen in APSGN. In the present study, cardiac tissue material from rabbits injected with GAS was investigated. After 8 or more weeks of intravenous (i.v.) injections, minimal changes were seen in those animals receiving an IgG non-binding GAS strain, type T27, whereas those animals receiving either of two IgG-binding GAS strains, types M1 or M22, developed strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence of streptococcal IgG-binding activity. Our results demonstrate that myocardial tissue changes may be induced in the rabbit by i.v. injection of whole heat-killed GAS of at least two M serotypes. Conceivably, induction of immune complexes by bacterial IqG BPs may lead to myocardial deposition of IgG, in turn triggering a series of events, involving the complement system and proinflammatory cytokines, with resulting tissue damage. Though many virulence factors may be involved in the development of ARF and APSGN, and a given GAS strain will never cause both, our results may suggest a new pathogenetic mechanism common to these two major non-suppurative complications.
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| 9. |
- Forsum, Urban, 1946-, et al.
(författare)
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Bacterial vaginosis--a microbiological and immunological enigma.
- 2005
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0903-4641 .- 1600-0463. ; 113:2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- The development of bacterial vaginosis (BV) among women of childbearing age and the resulting quantitative and qualitative shift from normally occurring lactobacilli in the vagina to a mixture of mainly anaerobic bacteria is a microbiological and immunological enigma that so far has precluded the formulation of a unifying generally accepted theory on the aetiology and clinical course of BV. This critical review highlights some of the more important aspects of BV research that could help in formulating new basic ideas respecting the biology of BV, not least the importance of the interleukin mediators of local inflammatory responses and the bacterial shift from the normally occurring lactobacilli species: L. crispatus, L. gasseri, L. jensenii, and L. iners to a mixed flora dominated by anaerobic bacteria.
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| 10. |
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| 11. |
- Holl, Katsiaryna, et al.
(författare)
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Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study
- 2008
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - Oxford : Wiley. - 1600-0463 .- 0903-4641. ; 116:9, s. 816-822
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Tidskriftsartikel (refereegranskat)abstract
- During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73: 95% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age(OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.
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| 12. |
- Karpman, Diana, et al.
(författare)
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The contact/kinin and complement systems in vasculitis.
- 2009
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Ingår i: APMIS Acta Pathologica, Microbiologica et Immunologica Scandinavica. Supplementum. - : Wiley. - 0903-465X. ; 117, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Vasculitides are a group of conditions with marked inflammation in and around vessel walls and vascular leakage. These conditions may involve the presence of auto-antibodies such as ANCA or may be mediated by other autoimmune or pathogenic mechanisms. Regardless of the primary trigger, vasculitides entail activation of the complement system as well as the contact/kinin system. In vivo and in vitro data support the involvement of these systems showing activation of the alternative, classical and lectin complement pathways as well as release of bradykinin at sites of vascular inflammation. This short review will summarize some of the data regarding the participation of these systems and the interplay between the complement and kinin systems as well as their interaction with the endothelium and neutrophils. Although these systems do not play a primary role in induction of vasculitis, the peptides released contribute to inflammation and vascular leakage and may thus be identified as potential therapeutic targets.
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| 13. |
- Tjernberg, Ivar, 1973-, et al.
(författare)
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C6-peptide serology as diagnostic tool in neuroborreliosis
- 2008
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 116:5, s. 393-399
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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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| 14. |
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| 15. |
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| 16. |
- Hallander, Hans, et al.
(författare)
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Seroprevalence of pertussis antitoxin (anti-PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program
- 2009
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - New York, USA : Wiley. - 0903-4641 .- 1600-0463. ; 117:12, s. 912-922
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of IgG ELISA antibodies against pertussis toxin (anti-PT) was studied in two Swedish seroepidemiological studies. One was performed in 1997 when the new pertussis vaccination program was 1 year old (n = 3420). In 2007, when Pa vaccines had been used countrywide for 10 years in the universal child vaccination program, this study was repeated to analyze the effect of vaccination on anti-PT prevalence (n = 2379). Before the statistical analysis of seroprevalence, children vaccinated within the last 2 years before the serosurveys were excluded. The results indicate a reduced exposure to Bordetella pertussis in the population. The proportion of sera without measurable anti-PT antibodies increased significantly, aggregated over all comparable age groups, from 3.8% in people sampled in 1997 to 16.3% in people sampled in 2007. For cord blood, 1% was without measurable anti-PT antibodies in 1997 compared to a significantly higher level, 12%, in 2007. With anti-PT concentrations of ≥50 and ≥100 EU/ml as cutoff points for 'recent infection' the proportion above the cutoff points for younger children was significantly higher in 1997 than in 2007 at both cutoff points. For all adults, 20 years of age and older, the difference in proportions above the lower cutoff point was close to statistically significant, comparing 1997 with 2007. This was not the case at 100 EU/ml. In the 1997 samples of children, there was a significant downward trend of 'recent infections' at both cutoff points for three sampled age groups between 5 and 15 years of age from 21% at 5.0–5.5 years of age to 7% at 14.7–15.7 years for the lowest cutoff. In the 2007 samples of children, on the contrary, there was a significant continuous upward trend of 'recent infections', at both cutoff points, for four sampled age groups between 4 and 18 years of age – from 4% at 4–5 years of age to 16% at 17–18 years at the lowest cutoff. The continuous increase, with age of children with high anti-PT concentrations, supports the recent change in the general Swedish childhood vaccination program to include a pre-school booster at 5–6 years and a school-leaving booster at 14–16 years of age.
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| 17. |
- Kühme, Tobias, et al.
(författare)
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Wound contamination in cardiac surgery, a systematic quantitative and qualitative study of bacterial growth in sternal wounds in cardiac surgery patients
- 2007
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 115, s. 1001-1007
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the degree of bacterial contamination in the sternal wound during cardiac surgery and the sternal skin flora after operation in order to increase our understanding of the pathogenesis of sternal wound infections. Design: Prospective study where cultures were taken peri- and postoperatively from sternal wounds and skin. Setting: University Hospital. Patients: 201 cardiac surgery patients. Results: 89% of the patients grew bacteria from the subcutaneous sternal tissue. 98% of the patients showed bacterial growth on the surrounding skin at the end of the operation. We found both commensal and nosocomial bacteria in the sternal wound. These bacteria had different temporal distribution patterns. Coagulase-negative staphylococci (CoNS) and Propionibacterium acnes (PA) were by far the most prevalent bacteria during and after the operation. Furthermore, 41% of patients had more than 10 000 CFU/pad CoNS on the skin. There was no correlation between length of operation and number of bacteria. Men displayed higher bacterial counts than women on the skin. Conclusion: Skin preparation with ethanol/chlorhexidine is unable to suppress the physiological skin flora for the duration of a heart operation. A decrease of CoNS and PA postoperatively can be caused by competitive recolonisation of commensal and nosocomial bacteria.
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| 18. |
- Scherstén, Henrik, 1956
(författare)
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Modified prophylaxis for preventing deep sternal wound infection after cardiac surgery.
- 2007
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0903-4641. ; 115:9, s. 1025-8
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Tidskriftsartikel (refereegranskat)abstract
- In order to prevent deep sternal wound infection after cardiac surgery we decided at the Sahlgrenska University Hospital to revise our protocol for antibiotic prophylaxis by adding an application of local collagen-gentamicin between the sternum halves to our standard prophylaxis. In addition, we focused specifically on the wiring technique. This quite simple modification of the prophylaxis program has been successful. The infection rate during 2006 is the lowest rate we have recorded since we started measuring it in 1995. We conclude that with application of local collagen-gentamicin and modification of the sternal closure method we have been able to significantly decrease the incidence of wound infections after cardiac surgery.
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| 19. |
- Ståhle, Elisabeth, et al.
(författare)
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Workshop : summary of discussions and conclusions.
- 2007
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 115:9, s. 1032-1035
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Tidskriftsartikel (refereegranskat)
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| 20. |
- Eriksson, K., et al.
(författare)
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Validation of the use of Pap-stained vaginal smears for diagnosis of bacterial vaginosis
- 2007
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 115:7, s. 809-813
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Tidskriftsartikel (refereegranskat)abstract
- Papanicolaou-stained cervicovaginal smears (Pap smears) are used to screen for cervical cancer. Since there is a lack of consensus in published reports respecting the efficacy of Pap-stained smears in BV diagnostics, there is a need to validate their use for diagnosis of BV. Slides from the international BV00 workshop were Pap stained and independently analyzed by four investigators under a phase-contrast microscope. All workshop slides-whether Pap-stained, Gram-stained or rehydrated air-dried smears-were scored according to the same Nugent classification. The diagnostic accuracy of Pap smears for diagnosis of BV had a sensitivity of 0.85 and a specificity of 0.92, with a positive and negative predictive value of 0.84 and 0.93, respectively. The interobserver weighted kappa index was 0.86 for Pap-stained smears compared to 0.81 for Gram-stained smears, and 0.70 for rehydrated air-dried smears using the mean Nugent score as the criterion standard. Provided that the samples are taken from equivalent locations (the vaginal fornix) and analyzed according to the same scoring criteria, there is no discernable difference in the diagnostic accuracy of the three smear-staining methods. The Pap-stained vaginal smears can be used as a wholly adequate alternative to Gram-stained smears for BV diagnosis.
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| 21. |
- Fernebro, Josefin, et al.
(författare)
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Standardizing evaluation of sarcoma proliferation - higher Ki-67 expression in the tumor periphery than the center
- 2007
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 115:6, s. 707-712
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue sarcomas often present as large and histopathologically heterogenous tumors. Proliferation has repeatedly been identified as a prognostic factor and immunostaining for Ki-67 represents the most commonly used proliferation marker. There is, however, a lack of consensus on how to evaluate Ki-67 staining regarding optimal cut-off levels, selection of tumor areas, and the number of tumor cells to evaluate. We assessed the impact of targeting peripheral versus central tumor areas using tissue microarray-based staining for Ki-67 throughout the tumor diameter in 25 leiomyosarcomas. In 18/25 tumors, Ki-67 expression was higher in the tumor periphery. If 10% staining tumor nuclei was used as cut-off and the maximal Ki-67 staining section in the tumor periphery was considered, 21/25 tumors would have been classified as highly proliferative compared to 14/25 if the tumor center had been analyzed. Similar results were obtained also when higher cut-off levels were used and if the mean expression rather than the maximal expression was considered and the differences were neither caused by necrosis nor by hypoxia (assessed as HIF-1 alpha expression). Our findings suggest that the determination of proliferation in soft tissue sarcomas should be standardized for clinical application of Ki-67 as a prognostic marker.
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| 22. |
- Foglé-Ansson, Margaretha, et al.
(författare)
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Otomicroscopic findings and systemic interleukin-6 levels in relation to etiologic agent during experimental acute otitis media
- 2006
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 114:4, s. 285-291
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to explore whether it was possible to differentiate the clinical course and the otomicroscopic appearance of acute otitis media (AOM) caused by common otitis pathogens in an animal model. Systemic interleukin (IL)-6 levels as early markers for bacterial AOM were also studied. Four groups of rats were inoculated with either Streptococcus pneumoniae, Streptococcus pyogenes, non-typeable Haemophilus influenzae or Moraxella catarrhalis. The animals were monitored by otomicroscopy, photos of the tympanic membrane, cultures and IL-6 detection in serum the following 4 days. The gram-positive S. pneumoniae and S. pyogenes induced severe AOM with opaque effusion behind the tympanic membrane, pronounced dilation of the vessels and spontaneous perforations. The gram-negative H. influenzae and M. catarrhalis induced a less severe infection with cloudy, sometimes foamy effusion, and no spontaneous perforations. With the otomicroscopic findings it was possible to distinguish between infections induced by gram-positive bacteria and gram-negative bacteria. Detection of interleukin-6 in serum appeared to be of limited use for all infections except the pneumococcal AOM, but this needs to be further investigated.
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| 23. |
- Guo, Xiao-Hua, et al.
(författare)
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Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells
- 2006
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 114:12, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.
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| 24. |
- Karlsson, Eva, et al.
(författare)
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Nontypeable Haemophilus influenzae strains with the capsule-associated insertion element IS1016 may mimic encapsulated strains
- 2006
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 114:9, s. 633-640
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Tidskriftsartikel (refereegranskat)abstract
- With the elimination of Haemophilus influenzae type b through vaccination, it has been suggested that other types of H. influenzae strains might acquire virulence traits and emerge as important pathogens. The gene sequence IS1016 has been associated with an increased capacity to cause severe infections. It is usually present in encapsulated strains but is sometimes harbored by nontypeable H. influenzae strains. To explore this further, 118 H. influenzae isolates, collected from both patients and healthy carriers, were investigated with PCR with reference to this gene sequence. Isolates positive for the insertion element were bio- and serotyped. The presence of hmw genes for adherence, the genetic profile, and the ability to form biofilm in vitro were investigated. A total of 15 isolates were IS1016-positive, whereof 12 were nontypeable. All 12 nontypeable isolates were obtained from healthy carriers, and 92% of the isolates were biotype I. They cross-reacted to some extent with type-specific antisera or exhibited a restricted genetic diversity like encapsulated strains. Furthermore, they lacked hmw-genes, and their ability to form biofilms was comparable with a capsule-deficient type b strain. Although this subset of strains mimicked traits usually exhibited by encapsulated strains, the isolation frequency did not seem to have been affected by vaccination.
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| 25. |
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