| 1. |
- Welinder, Charlotte, et al.
(författare)
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A new murine IgG1 anti-Tn monoclonal antibody with in vivo anti tumour activity.
- 2011
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 21:8, s. 1097-1107
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Tidskriftsartikel (refereegranskat)abstract
- The Tn antigen (GalNAc alpha-O-Ser/Thr) is heterogeneously synthesised by a variety of tumours and contains an epitope defined by lectins and antibodies as a cluster of alpha GalNAc carbohydrates synthesised within a peptide sequence, which is rich in serine and/or threonine. The Tn antigen has been utilized as a target in vaccine experiments and also used as a biomarker for prognosis of different cancer forms. In this paper we present a new monoclonal antibody, GOD3-2C4, with the clear hallmarks of an anti-Tn antibody. It was generated through somatic cell hybridisation after immunisation of a mouse with a tumour cell line and a Tn carrying mucin. The antibody recognises synthetic Tn antigen and binds breast, colon, lung, ovarian and pancreas cancer. The GOD3-2C4 antibody has ADCC activity against Jurkat cells in vitro and for the first time it can be shown that an anti-Tn antibody has a significant in vivo effect on a human cancer cell line grown as a xenograft in SCID mice.
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| 2. |
- Björkqvist, Maria, et al.
(författare)
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Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn
- 2002
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 110:4, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Coagulase-negative staphylococci (CNS) are the leading cause of late-onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety-seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Örebro, Sweden in 1983–1997 were analysed. Twenty-nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed-field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.
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| 3. |
- Fredlund, Jan O, et al.
(författare)
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Abnormal DNA synthesis in polyamine deficient cells revealed by bromodeoxyuridine-flow cytometry technique
- 1994
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Ingår i: Cell Proliferation. - : Wiley. - 1365-2184 .- 0960-7722. ; 27:5, s. 243-256
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Tidskriftsartikel (refereegranskat)abstract
- Chinese hamster ovary cells were seeded in the absence or presence of the polyamine synthesis inhibitor 2-difluoromethylornithine (DFMO). At 1-4 days after seeding, the cells were labelled for 15-120 min with the thymidine analogue bromodeoxyuridine (BrdUrd) and they were then fixed directly after the labelling period. In addition, cells were labelled for 30 min and they were then allowed to progress in BrdUrd-free medium during a defined post-labelling time before fixation. An indirect immunofluorescence technique, using the monoclonal BrdUrd antibody and the intercalating stochiometric DNA stain, propidium iodide, was applied to enable quantification of cellular BrdUrd and DNA contents, respectively, by flow cytometry (FCM). By comparing the mean DNA content of BrdUrd-labelled cells to the mean DNA contents of G(1) and G(2) cells, a relative measure of the position of the BrdUrd-labelled cells was obtained (relative movement). Relative movement data, obtained from control and DFMO-treated cells fixed directly after BrdUrd labelling, indicated that DFMO-treated cells entered S phase at a normal rate, while their progression through S phase was impaired. DNA histograms of BrdUrd-labelled control cells fixed directly after labelling showed that most cells were found in early and late S phase, while DNA histograms of BrdUrd-labelled DFMO-treated cells showed that most cells were in early S phase, indicating a delayed progression through S phase. Analysis of relative movement of cells that were allowed to progress in BrdUrd-free medium after labelling showed that DFMO treatment resulted in a significant lengthening of the DNA synthesis time. Labelling index was significantly higher in DFMO-treated, growth-inhibited cells than in early plateau phase control cells indicating an S phase accumulation in the former cells.
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| 4. |
- Hansson, Jenny, et al.
(författare)
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Use of snus and acute myocardial infarction: pooled analysis of eight prospective observational studies
- 2012
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 27:10, s. 771-779
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Tidskriftsartikel (refereegranskat)abstract
- The use of snus (also referred to as Scandinavian or Swedish moist smokeless tobacco), which is common in Sweden and increasing elsewhere, is receiving increasing attention since considered a tobacco smoke "potential reduction exposure product". Snus delivers a high dose of nicotine with possible hemodynamic effects, but its impact on cardiovascular morbidity and mortality is uncertain. The aim of this study was to investigate whether snus use is associated with risk of and survival after acute myocardial infarction (AMI). Data from eight prospective cohort studies set in Sweden was pooled and reanalysed. The relative risk of first time AMI and 28-day case-fatality was calculated for 130,361 men who never smoked. During 2,262,333 person-years of follow-up, 3,390 incident events of AMI were identified. Current snus use was not associated with risk of AMI (pooled multivariable hazard ratio 1.04, 95 % confidence interval 0.93 to 1.17). The short-term case fatality rate appeared increased in snus users (odds ratio 1.28, 95 % confidence interval 0.99 to 1.68). This study does not support any association between use of snus and development of AMI. Hence, toxic components other than nicotine appear implicated in the pathophysiology of smoking related ischemic heart disease. Case fatality after AMI is seemingly increased among snus users, but this relationship may be due to confounding by socioeconomic or life style factors.
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| 5. |
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| 6. |
- Jansson, Jan-Håkan, et al.
(författare)
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Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- Background. Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. Objective. The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. Methods. Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. Results. No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). Conclusion. Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.
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| 7. |
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| 8. |
- Thunberg, Ulrica, 1967-, et al.
(författare)
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Anti-Staphylococcal humoral immune response in patients with chronic rhinosinusitis
- 2019
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Ingår i: Rhinology Online. - : European Rhinologic Society. - 2589-5613. ; 2, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Staphylococcus aureus (S. aureus) can behave both as a harmless commensal and as a pathogen. Its significance in the pathogenesis of chronic rhinosinusitis (CRS) is not yet fully understood. This study aimed to determine serum antibody re-sponses to specific staphylococcal antigens in patients with CRS and healthy controls, and to investigate the correlation between specific antibody response and severity of symptoms.Methodology: Serum samples from 39 patients with CRS and 56 healthy controls were analysed using a protein microarray to investigate the antibody response to S. aureus specific antigens, with a focus on immunoglobulin G (IgG) directed toward stap-hylococcal components accessible to the immune system. Holm-Bonferroni corrections were applied in all analyses. Information about growth of S. aureus in nares and maxillary sinus was taken from a previous study based on the same individuals. Clinical symptoms were assessed using a scoring system.Results: IgG antibody levels toward staphylococcal TSST-1 and LukF-PV were significantly higher in the CRS patient group com-pared to healthy controls, and levels of anti-TSST-1 antibodies were significantly higher in the CRS patient group with S. aureus in maxillary sinus than in controls. There were no correlations between the severity of symptoms and levels of serum anti-staphylo-coccal IgG antibody levels for LukF-PV and TSST-1.Conclusions: TSST-1 and LukF-PV could be interesting markers for future studies of the pathogenesis of CRS.
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| 9. |
- Thunberg, Ulrica, 1967-
(författare)
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Aspects of Staphylococcus aureus in Chronic Rhinosinusitis
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic rhinosinusitis (CRS) affects about 10% of the European population, and is considered a great scourge. Its cause is not clear. Findings of Staphylococcus aureus in the maxillary sinus are common in CRS patients, but are usually regarded as insignificant due to the bacterium’s attribute as a commensal elsewhere. S. aureus has the ability to cause both mild disease and serious conditions, due to its wide armoury of secreted components such as staphylococcal enterotoxins and cell-surface-associated virulence components. This thesis focuses on the clinical features and importance of S. aureus in CRS, including a long-term perspective on the disease, through studying a cohort of CRS patients. S. aureus was found to be highly prevalent in the maxillary sinus and nares of CRS patients, which might indicate an impact on the disease. A sheltered sampling technique for maxillary sinus culture reduced the contamination rate but did not significantly improve the diagnostic reliability. Whole genome sequencing showed that 95% of paired S. aureus isolates collected simultaneously from the nares and maxillary sinus were from identical lineages, indicating colonization of the maxillary sinus from the nares as one joint milieu. A decade-long persistence of S. aureus in the nares and maxillary sinus was established in 20% of CRS patients. The vast majority of S. aureus isolates were susceptible to all tested antibiotics, including the strains that had persisted for a decade. No significant differences in the prevalence of gene determinants were seen for selected virulence factors and MSCRAMMs in S. aureus isolates sampled from CRS patients and healthy controls. The overall alterations of anti-staphylococcal antibodies over time showed great variability and minor support for an impact of S. aureus on CRS. At the long-term follow-up, symptoms were generally reduced and VAS quality of life in terms of fatigue was improved. The subgroup of CRS patients without nasal polyposis had a greater chance of symptom relief than their counterparts with nasal polyposis in this longterm perspective. There was no correlation between severity of symptoms for CRS patients and S. aureus growth in the maxillary sinus to support a role for S. aureus in CRS.
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