| 1. |
- Orlova, Anna, et al.
(författare)
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Cellular processing of (125)I- and (111)in-labeled epidermal growth factor(EGF) bound to cultured A431 tumor cells
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 827-35
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Tidskriftsartikel (refereegranskat)abstract
- Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell.
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| 2. |
- Orlova, Anna, et al.
(författare)
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Cellular processing of 125I- and 111in-labeled epidermal growth factor (EGF) bound to cultured A431 tumor cells
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 827-835
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell.
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| 3. |
- Orlova, Anna, et al.
(författare)
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Cellular processing of indirectly astatinated and iodinated mAb A33 in SW1222 cultured cells
- 2001
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 44:suppl 1, s. S715-S717
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- In principle, alpha-emitting radionuclides, such as 211At, are more efficient than beta-emitters to inactive single disseminated cancer cells. However, cellular processing of astatinated proteins has not yet been studied in detail. In this study an anti-colorectal cancer monoclonal antibody (mAb) A33 was indirectly labeled with 211At and for comparison with 125I. Binding and retention of radioactivity was studied in the colorectal cancer cell-line SW1222. A similar pattern of binding and retention of the two radiohalogens was seen. The main difference found, that the retention time of astatinated mAb in SW1222 was almost two times longer, might be of advantage in radionuclide therapy.
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| 4. |
- Orlova, Anna, et al.
(författare)
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Targeting against epidermal growth factor receptors : Cellular processing of astatinated EGF after binding to cultured carcinoma cells
- 2004
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 24:6, s. 4035-4042
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The alpha-emitting nuclide 211At is of great interest for radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g. epidermal growth factor (EGF) the receptors of which are overexpressed in many malignancies. However, almost no information concerning the cellular processing of astatinated targeting agents is available.MATERIALS AND METHODS:We indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular processing in A-431 carcinoma cells in comparison with data concerning [125I]-benzoate-EGF.RESULTS: The biological half-life of astatine (3.5 h) was longer than the half-life of the iodine label (1.5 h). The increase of the half-life was due to longer retention of the internalised astatine radioactivity. The maximum accumulation for the astatine label occurred later (4-6h) than that for the iodine label (2-4h), indicating a slower excretion of astatine that was confirmed in experiment with 211At/1251-benzoate-EGF.CONCLUSION:The long retention of astatine might be advantageous for radionuclide therapy.
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| 5. |
- Ahlgren, Ewa, 1959-, et al.
(författare)
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Neurocognitive impairment and driving performance after coronary artery bypass surgery
- 2003
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 23:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neurocognitive impairment is common after cardiac surgery but few studies have examined the relationship between postoperative neuropsychological test performance and everyday behavior. The influence of postoperative cognitive impairment on car driving has previously not been investigated. The purpose of this study was to evaluate neurocognitive function and driving performance after coronary artery bypass grafting (CABG).Methods: Twenty-seven patients who underwent coronary artery bypass grafting with standard cardiopulmonary bypass technique and 20 patients scheduled for percutaneous coronary intervention (PCI) under local anesthesia (control group) were enrolled in this prospective study conducted from April 1999 to September 2000. Complete data were obtained in 23 and 19 patients, respectively. The patients underwent neuropsychological examination with a test battery including 12 tests, a standardized on-road driving test and a test in an advanced driving simulator before and 4–6 weeks after intervention.Results: More patients in the coronary artery bypass grafting group (n=11, 48%) than in the percutaneous coronary intervention group (n=2, 10%) showed a cognitive decline after intervention (P=0.01). In the on-road driving test, patients who underwent coronary artery bypass grafting deteriorated after surgery in the cognitive demanding parts like traffic behavior (P=0.01) and attention (P=0.04). Patients who underwent percutaneous intervention deteriorated in maneuvering of the vehicle (P=0.04). No deterioration was detected in the simulator in any of the groups after intervention. Patients with a cognitive decline after intervention also tended to drop in the on-road driving scores to a larger extent than did patients without a cognitive decline.Conclusion: This study indicates that cognitive functions important for safe driving may be influenced after cardiac surgery.
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| 6. |
- Brismar, Anna, 1971-
(författare)
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Environmental considerations in the planning of large dam projects : a study on Environmental Impact Statements and the Southeastern Anatolia Project
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Large dam projects have played a key role in supporting societal development in the past and continue to be launched, primarily in developing countries. However, large dam projects also cause extensive environmental impacts in the river system, which may reduce the river system's capacity to provide goods, services, and other values apart from those generated by the project. The Environmental Impact Statement (ElS) has become a key instrument for enabling prevention, minimization, and mitigation of significant adverse environmental effects of major projects in early planning. The potential of EISs to support compromise building between conflicting interests is also increasingly recognized. In reality, the great potentials of the ElS are rarely fully utilized, which motivate further improvements.This thesis has three main objectives, Le. (i) to examine the motives behind large dam projects, their impact on project planning, and some constraints for full project realization, (ii) to identify shortcomings in EISs and other project-related reports regarding the extent to and manner in which potential environmental effects of large dam projects are attended to, and (iii) to suggest measures for how to improve the capacity of EISs to support impact minimization and compromise building in project plarming and decision-making.Based on a case study on the Southeastern Anatolia Project (GAP) in southeast Turkey, it was found that the objectives and planning of large dam projects can change significantly over time, in response to changes in the underlying ambitions and motives for development. While changes to the design may increase the dam's technical capacity to store water and generate hydropower, the actual potential to utilize its installed capacities during recurrent droughts may be limited. An increased scale and number ofdam project objectives may also lead to increased competition over the river water. Full realization of dam project objectives may be hampered by the climate and by growing water demands of competing uses. Moreover, an analysis of GAP-related reports revealed imbalances in the total degree of attention given to individual environmental problems, different categories of environmental problems, and to environmental problems of dam projects and irrigation schemes, respectively, as weIl as shifts in the focus of attention over time from early plarming to implementation. The fmdings suggest that project-related reports tend to focus on problematic environmental conditions that motivate project implementation, and on potential environmental effects that may undermine project productivity, viability, or longevity, particularly in planning and early implementation. In contrast, those potential environmental effects with no apparent bearing on the financial or operational success of the project tend to be largely neglected unless strong incentives are created.The analysis ofEISs of large dam projects revealed shortcomings in the attention given to root causes and impact pathways involved in the generation of higher-order environmental effects and cumulative impacts. Important imbalances were also found in the degree of attention given to different types of environmental effects. In order to improve the capacity of EISs to explain how higher-order effects and cumulative impacts may arise, network analysis and cause-effect diagrams should be increasingly adopted. This thesis also proposes a conceptual framework to facilitate a comparison of desired and undesired effects, based on the view of a river system as a provider of goods and services, which enables the translation of ecological effects into their societal and economic implications.
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| 7. |
- Dolby, Viveka, et al.
(författare)
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Overexpression and functional characterisation of the human melanocortin 4 receptor in Sf9 cells
- 2004
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 37:2, s. 455-461
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Tidskriftsartikel (refereegranskat)abstract
- The human melanocortin 4 receptor (MC4r) was successfully expressed in Sf9 cells using the baculovirus infection system. N- and C-terminally His-tagged receptors generated B-max values of 14 and 23 pmol receptor/mg membrane protein, respectively. The highest expression level obtained with the C-terminally His-tagged MC4r corresponded to 0.25 mg active receptor/litre culture volume. Addition of a viral signal peptide at the N-terminus of the His-tagged MC4r did not improve the expression level. Confocal laser microscopy studies revealed that both the N- and C-terminally tagged MC4r did not accumulate intracellularly and were mainly located in the plasma membrane. The recombinant receptors showed similar affinity for the agonist NDP-MSH (K-d = 11 nM) as to MC4r expressed in mammalian cells. Functional coupling of the highest expressed C-terminal tagged receptor to endogenous Galpha protein was demonstrated through 6TPgammaS binding upon agonist stimulation of the receptor. K-i values for the ligands MTII, HS014, alpha-, beta-, and gamma-MSH are comparable to the values obtained for MC4r expressed in mammalian cells. (C) 2004 Elsevier Inc. All rights reserved.
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| 8. |
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| 9. |
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| 10. |
- Höglund, Johanna, et al.
(författare)
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Optimized indirect (76)Br-bromination of antibodies using N-succinimidyl para-[76Br]bromobenzoate for radioimmuno PET
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 837-43
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibody 38S1 was radiobrominated with the positron emitter (76)Br (T(1/2) = 16.2 h). Indirect labeling was performed using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB) as the precursor molecule. SPMB was labeled using Chloramine-T yielding N-succinimidyl para-[(76)Br]bromobenzoate, which was then conjugated to the antibody. Optimization of the labeling conditions and further conjugation gave a total yield ( mean+/-max error) of 49+/-2%. The immunoreactivity of the antibodies was retained after labeling. Thus, antibodies intended for positron emission tomography can be labeled with (76)Br, which gives high yields and preserved immunoreactivity when using the SPMB technique described.
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