| 1. |
- Falck, Anna-Karin, et al.
(författare)
-
Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study
- 2012
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods: Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results: DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63-2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions: The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.
|
|
| 2. |
- Grdic Eliasson, Dubravka, et al.
(författare)
-
A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.
- 2011
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 29:23, s. 3951-61
-
Tidskriftsartikel (refereegranskat)abstract
- Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation.
|
|
| 3. |
|
|
| 4. |
- Berrocal, Carlos Gil, 1986, et al.
(författare)
-
Experimental Investigation on Rebar Corrosion in Combination with Fibres
- 2014
-
Ingår i: Proceedings of the XXII Nordic Concrete Research Symposium. - 9788282080439 ; , s. 532-
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, early results from an on-going project aimed at investigating the influence of fibre reinforcement on corrosion of rebar are presented. Resistivity of mixes containing fibres was reduced when compared with plain concrete while chloride migration seemed to remain unaffected. On the mechanical properties, results showed that while the flexural behaviour was greatly enhanced by addition of fibres up to 0.5% vol., the variation in compressive strength was negligible regardless of the fibre type. Early results from the main experiments indicated atendency of earlier corrosion initiation with increasing crack width, and that the initiation time was somewhat delayed for the fibre reinforced specimens.
|
|
| 5. |
- Berrocal, Carlos Gil, 1986, et al.
(författare)
-
INFLUENCE OF STEEL FIBRES ON CORROSION OF REINFORCEMENT IN CONCRETE IN CHLORIDE ENVIRONMENTS: A REVIEW
- 2013
-
Ingår i: 7th International Conference FIBRE CONCRETE 2013 Proceedings. - 9788001052396
-
Konferensbidrag (refereegranskat)abstract
- This paper presents various durability aspects of steel-fibre reinforced concrete (SFRC). Published research results show that due to the limited length of the fibres and the casting conditions, steel fibres embedded in concrete show no corrosion signs despite high chloride concentrations. It was also reported that due to the fibres’ ability to arrest crackwidth propagation, permeability was positively affected for cracked concrete compared with plain concrete. Recent research suggested that some of the fibres might beinterconnected and in contact with the ordinary steel reinforcement, forming a galvanic couple where the fibres would act as sacrificial anodes protecting the rebar and reducing or even stopping the corrosion process. Based on reviewed durability properties, it is argued that steel fibres could be used in reinforced concrete (RC) structures exposed to chloride environments to improve their overall durability performance. However, further experimental results supporting this hypothesis are needed.
|
|
| 6. |
|
|
| 7. |
- Carlsson, Marcus, et al.
(författare)
-
Cardiac output and cardiac index measured with cardiovascular magnetic resonance in healthy subjects, elite athletes and patients with congestive heart failure
- 2012
-
Ingår i: Journal of Cardiovascular Magnetic Resonance. - 1097-6647. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular Magnetic Resonance (CMR) enables non-invasive quantification of cardiac output (CO) and thereby cardiac index (CI, CO indexed to body surface area). The aim of this study was to establish if CI decreases with age and compare the values to CI for athletes and for patients with congestive heart failure (CHF). Methods: CI was measured in 144 healthy volunteers (39 +/- 16 years, range 21-81 years, 68 females), in 60 athletes (29 +/- 6 years, 30 females) and in 157 CHF patients with ejection fraction (EF) below 40% (60 +/- 13 years, 33 females). CI was calculated using aortic flow by velocity-encoded CMR and is presented as mean +/- SD. Flow was validated in vitro using a flow phantom and in 25 subjects with aorta and pulmonary flow measurements. Results: There was a slight decrease of CI with age in healthy subjects (8 ml/min/m(2) per year, r(2) = 0.07, p = 0.001). CI in males (3.2 +/- 0.5 l/min/m(2)) and females (3.1 +/- 0.4 l/min/m(2)) did not differ (p = 0.64). The mean +/- SD of CI in healthy subjects in the age range of 20-29 was 3.3 +/- 0.4 l/min/m(2), in 30-39 years 3.3 +/- 0.5 l/min/m(2), in 40-49 years 3.1 +/- 0.5 l/min/m(2), 50-59 years 3.0 +/- 0.4 l/min/m(2) and >60 years 3.0 +/- 0.4 l/min/m(2). There was no difference in CI between athletes and age-controlled healthy subjects but HR was lower and indexed SV higher in athletes. CI in CHF patients (2.3 +/- 0.6 l/min/m(2)) was lower compared to the healthy population (p < 0.001). There was a weak correlation between CI and EF in CHF patients (r(2) = 0.07, p < 0.001) but CI did not differ between patients with NYHA-classes I-II compared to III-IV (n = 97, p = 0.16) or patients with or without hospitalization in the previous year (n = 100, p = 0.72). In vitro phantom validation showed low bias (-0.8 +/- 19.8 ml/s) and in vivo validation in 25 subjects also showed low bias (0.26 +/- 0.61 l/min, QP/QS 1.04 +/- 0.09) between pulmonary and aortic flow. Conclusions: CI decreases in healthy subjects with age but does not differ between males and females. We found no difference in CI between athletes and healthy subjects at rest but CI was lower in patients with congestive heart failure. The presented values can be used as reference values for flow velocity mapping CMR.
|
|
| 8. |
- Eloranta, Maija-Leena, et al.
(författare)
-
Type I interferon system activation and association with disease manifestations in systemic sclerosis
- 2010
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:7, s. 1396-1402
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFNalpha) and chemokines of importance in the disease process. METHODS: Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFNalpha produced and serum levels of IFNalpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc. RESULTS: Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjögren syndrome antigen autoantibodies. The pDCs were responsible for the IFNalpha production which required interaction with FcgammaRII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFNalpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFNalpha (p=0.029). CONCLUSION: An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.
|
|
| 9. |
- Granath, Britta, 1982, et al.
(författare)
-
A comparison of the humoral immune response induced by a recombinant human protein in wild type mice and in transgenic mice expressing the protein
- 2014
-
Ingår i: British Journal of Pharmaceutical Research. - 2231-2919. ; 4:21, s. 2511-2524
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this work was to investigate the correlation between anti drug antibody (ADA) induction and how different manufacturing processes of biopharmaceuticals affect the immunogenicity of the protein. This was done by testing four different batches of the same recombinant human protein in transgenic (Tg) mice. Methodology: Wild type (Wt) and human protein-transgenic (Tg) mice were challenged by repeated subcutaneous injections of four batches of a drug candidate protein, obtained by different purification methods. Differences between drug-specific IgG1, IgG2a, IgG2b, IgG3 and IgM antibody patterns produced in Tg vs. Wt mice were investigated and compared to the plasma cytokine profiles. A conventional ELISA was used as a reference method for ADA detection. Results: ADA responses detected in Tg mice were mainly of the IgG1 subclass and occurred only in significant response to the batch containing the highest level of proteins originating from the recombinant host cells. Wt mice, on the other hand, showed a combined IgG1/IgG2b response to all drug batches, except to the batch with the highest purity. The most pure batch failed to induce significant ADA in both Wt and Tg animals, suggesting host cell derived impurities to be a strong contributing factor to the antibody responses observed. Conclusion: Thus, an isolated IgG1 response in drug-tolerant Tg mice may serve as a potential biomarker of an immunological reaction to process-related impurities of the protein drug. In contrast, a combined IgG1/IgG2b-profile, as observed in immunoreactive Wt mice, more likely reflects a xeno-response.
|
|
| 10. |
- Jansson, Anette M, 1963, et al.
(författare)
-
Bond between Reinforcement and Self-Compacting Steel-Fibre-Reinforced Concrete
- 2012
-
Ingår i: Proceeding of the Fourth International Conference on Bond in Concrete 2012: Bond, Anchorage, Detailing. ; 1, s. 323-329
-
Konferensbidrag (refereegranskat)abstract
- In this study, pull-out tests of specimens with short embedment length and varying fibre content were carried out. The results showed no effect from the fibres on the bond-slip behaviour before peak load when normalized with respect to the compressive strength. After peak, the fibre reinforcement provided extra confinement, changing the failure mode from splitting to pull-out failure. The test results were used to calibrate a frictional bond model in non-linear finite element analyses. The model proved to yield results in good agreement with the experimental results regarding failure modes, load-slip relation and splitting strains on the surfaces of the pull-out specimens. The tests and analyses in combination confirmed that the fibre reinforcement neither disturbed nor improved the bond properties at the interface layer between reinforcement steel and concrete; i.e. the fibres only provided confinement to the surrounding structure.
|
|
