| 31. |
- Kus, Hulya, et al.
(författare)
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In-use performance of rendered autoclaved aerated concrete walls by long-term moisture monitoring
- 2004
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Ingår i: Building and Environment. - : Elsevier Ltd. - 0360-1323 .- 1873-684X. ; 39:6, s. 677-687
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Tidskriftsartikel (refereegranskat)abstract
- The importance of long-term performance and durability of building materials and components has received increasing consideration with regard to a sustainable built environment. Degradation due to exposure to environment conditions, particularly driving rain, play a significant role in the service life of porous materials used in external wall components. Microenvironment monitoring data are presented in this paper to show how different surface coatings can contribute to moisture performance of external walls made of autoclaved aerated concrete (AAC). Renderings modifed with hydrophobic products on AAC substrate prove to have less wetting and better drying properties than unmodified renderings according to the performance assessment based on the amount and duration of moisture measured in the material.
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| 32. |
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| 33. |
- Lindman, Henrik, 1963-
(författare)
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Individually Tailored Toxicity-based Chemotherapy : Studies on Patients with Primary and Metastatic Breast Cancer
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Standard dosing of chemotherapy based on body surface area (BSA) results in large individual differences in toxicity due to a large inter-patient variability in pharmacokinetics (PK) and pharmacodynamics (PD). This results in under-dosing in certain patients with a potentially weaker antitumoral effect.Three clinical studies of individually tailored dosing of chemotherapy, based on haematological toxicity were conducted. In the first study, 26 women with metastatic breast cancer were treated with tailored and dose-escalated 5-fluorouracil, epirubicin and cyclophosphamide, supported by G-CSF (dFEC). In the second study 525 patients with high-risk primary breast cancer were randomised between dFEC and high-dose chemotherapy with autologous bone-marrow transplantation. The feasibility of a FEC regimen with doubled cyclophosphamide dose to mobilise peripheral stem cells was investigated. In the third study, 44 metastatic patients were treated with tailored epirubicin and docetaxel (ET). PK and PD were also investigated in these patients. The potential effects of G-CSF on MRI tumour evaluation were studied in 18 patients with skeletal metastases.Toxicity-based dosing entailed an evenly distributed two- to three-fold range of tolerated doses in all three studies. Efficacy and toxicity were not correlated to tolerated dose-levels. Tailored dFEC resulted in a response rate of 81% and the same regimen resulted in fewer breast cancer relapses compared with standard FEC followed by high-dose therapy. Toxicity was manageable except for an increased rate of secondary leukaemia. The modified FEC could safely mobilise sufficient numbers of stem-cells. Tailored ET resulted in a response rate of 63%. The inter-individual variability in drug clearance was larger than the inter-occasion variability and a semi-physiological model of PK and PD could predict leukocyte nadir and duration. An increased diffuse MR signal in the long TE IR-TSE sequence was observed in normal bone-marrow during G-CSF treatment; this could be mistaken as disseminated metastatic disease and could obscure focal metastases.In conclusion, the concept of individually tailored toxicity-based dosage of chemotherapy was equally feasible in primary and metastatic breast cancer, in two different chemotherapy regimens and in treatment with or without G-CSF support and may provide a pragmatic way of overcoming the shortcomings of standard BSA-based dosing.
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| 34. |
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| 35. |
- Lövborg, Henrik, 1974-
(författare)
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Cellular Pharmacology of the Novel Antitumoural Cyanoguanidine CHS 828
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The antitumoural cyanoguanidine CHS 828 has shown promising activity in a number of preclinical and clinical studies. However, the mechanisms underlying the cell death induced by CHS 828 has not been clarified. This thesis describes in vitro studies of the cellular pharmacology of CHS 828.CHS 828 induced cell death with necrosis like features in the lymphoma cell line U-937 GTB. Addition of 3-aminobenzamide, an inhibitor of ADP-ribosylation, resulted in a decreased sensitivity to CHS 828 and a shift in the mode of cell death towards apoptosis. Mouse fibroblasts lacking the enzyme PARP-1 were more sensitive to CHS 828 compared to normal fibroblasts. CHS 828 was able to induce p53 in normal fibroblasts but this effect does not seem to be necessary to induce cell death.Characterization of two CHS 828 resistant cell lines indicated that they were selectively resistant to cyanoguanidines. Known mechanisms of anticancer drug resistance did not seem to account for the cyanoguanidine resistance. One possible resistance mediating protein, which was upregulated in the resistant cells, was epidermal fatty acid binding protein.A novel high content screening assay was also developed. The assay was shown to be suitable both for screening of potential novel antitumoural substances as well for mechanistic studies. In the assay, CHS 828 induced caspase-3 activity and reduction in mitochondrial membrane potential, both signs of apoptosis, in U-937 GTB cells. However, nuclei in exposed cells did not show nuclear fragmentation, one of the hallmarks of apoptosis.CHS 828 was also shown to indirectly inhibit the proteasome activity in U-937 GTB cells. In conclusion, the results presented provide new insights into the metabolic and molecular events involved in cell death induced by CHS 828.
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| 36. |
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| 37. |
- Lövborg, Henrik, et al.
(författare)
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Multiparametric evaluation of apoptosis : effects of standard cytotoxic agents and the cyanoguanidine CHS 828
- 2004
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Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 3:5, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- A multiparametric high-content screening assay for measurement of apoptosis was developed. HeLa cells and lymphoma U-937 cells were exposed to cytotoxic drugs in flat-bottomed optical microtiter plates. After incubation, the DNA-binding dye Hoechst 33342, fluorescein-tagged probes that covalently bind active caspases and chloromethyl-X-rosamine to detect mitochondrial membrane potential (MMP) were added. Image acquisition and quantitative measurement of fluorescence in a defined number of cells per well was performed using the automated image capture and analysis instrument ArrayScan. The usefulness of the assay was tested in cells exposed to standard cytotoxic drugs as well as in experimental cytotoxic cyanoguanidine CHS 828. A time- and dose-dependent activation of caspase-3, decrease in MMP, and increase in nuclear fragmentation and condensation were observed for the standard drugs, with the ability to correlate the parameters on a single cell basis. CHS 828 induced caspase-3 activation and reduction in MMP with modest changes in nuclear morphology. The method described was considered to be a rapid and information-rich apoptosis assay suitable both for correlating morphological and biochemical apoptotic events in single cells as well as for screening and evaluation of novel substances with apoptosis-inducing capabilities.
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| 38. |
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| 39. |
- Malmberg, Per, 1974, et al.
(författare)
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Subcellular localisation of cholesterol and phosphocholine with pattern-recognition-imaging-TOF-SIMS
- 2004
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Ingår i: Spectroscopy. ; 18:4, s. 503-512
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Tidskriftsartikel (refereegranskat)abstract
- Molecular ions of cholesterol, and its fragments, and phosphocholine fragments of phospholipids, were localized in single cells with a resolution of <1 μm. This is the first example of subcellular localisation of membrane lipids with pattern-recognition, imaging time-of-flight secondary ion mass spectrometry (PRITS) here utilized for identification and subcellular localisation of cholesterol and phosphocholine in PMN leukocytes. Cell imprints were produced by transferring the cell constituents of freeze-dried cells to a silver foil, and the silver surface was analyzed by TOF-SIMS. TOF-SIMS spectra were recorded by scanning the primary ion beam over the analysis area and acquiring a positive mass spectrum of the ions leaving the surface. Data were collected at either high mass resolution m/Δm>7000 or high lateral resolution. High mass resolution spectra were recorded on reference samples of pure cholesterol and phosphatidylcholine. Characteristic fragment peaks and the silver cationised quasimolecular ion [M+Ag]+ were selected as a pattern for the identification of the lipids in TOF-SIMS images of surface-adhering leukocytes. The localisation of membrane lipids showed lateral heterogeneity over the cell surface.
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| 40. |
- Malmberg, Per, 1974, et al.
(författare)
-
Subcellular localisation of cholesterol and phosphocholine with pattern-recognition-imaging-TOF-SIMS
- 2004
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Ingår i: Spectroscopy. ; 18:4, s. 503-512
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Tidskriftsartikel (refereegranskat)abstract
- Molecular ions of cholesterol, and its fragments, and phosphocholine fragments of phospholipids, were localized in single cells with a resolution of 7000 or high lateral resolution. High mass resolution spectra were recorded on reference samples of pure cholesterol and phosphatidylcholine. Characteristic fragment peaks and the silver cationised quasimolecular ion [M+Ag]+ were selected as a pattern for the identification of the lipids in TOF-SIMS images of surface-adhering leukocytes. The localisation of membrane lipids showed lateral heterogeneity over the cell surface.
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