| 1. |
- Borg, Åke, et al.
(author)
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Novel germline p16 mutation in familial malignant melanoma in southern Sweden
- 1996
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In: Cancer Research. - 0008-5472. ; 56:11, s. 500-2497
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Journal article (peer-reviewed)abstract
- The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.
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| 2. |
- Hakansson, Sara, et al.
(author)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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In: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Journal article (peer-reviewed)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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| 3. |
- Olsson, Sara, 1970-, et al.
(author)
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Ammonium tartrate as an ESR dosimeter material
- 1999
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In: Applied Radiation and Isotopes. - 0969-8043 .- 1872-9800. ; 50:5, s. 955-965
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Journal article (peer-reviewed)abstract
- This study is one step in the search for an ESR dosimeter material with a higher signal intensity than the commonly used l-α-alanine, to be useful in the clinical dose range (approximately 0.1–20 Gy). The substance ammonium tartrate was found and investigated regarding signal intensity, radical stability, dose response and dose resolution. The ESR signal intensity of ammonium tartrate was shown to be more than twice the intensity of the alanine signal. The data indicate that an unstable radiation induced radical contributes to the ESR signal initially; after a couple of hours it has converted to a secondary radical which has a decay slow enough to be considered stable during the first two weeks after irradiation. Ammonium tartrate has a linear dose response in the investigated range of 0.5–4000 Gy and a dose resolution of 0.1 Gy at the 0.5 Gy level where, as a comparison, the corresponding value for alanine is 0.3 Gy. We thus find the substance suitable for clinical dosimetry.
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| 4. |
- Olsson, Sara
(author)
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Calibration of an alanine/agarose gel
- 1998
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Reports (other academic/artistic)abstract
- In brachy therapy treatment, as well as in treatment with external beams, it is of crucial importance to thoroughly determine the absorbed dose in the tumour, in surrounding normal tissue and in risk organs. Several kinds of gel dosimeters have been, or are about to be, developed in order to get a three dimensional dosimeter, which would be very useful, especially in the context of brachy therapy. The need for high spatial resolution is raised by the fact that the absorbed dose decreases very fast with the distance from a brachy therapy source. The steep dose gradient also requires a dosimeter material with a wide dose range and no signal diffusion. Fe(II)/Fe(III) gel and polymer gels such as BANANA and BANG. These systems are analysed with magnetic resonance imaging (MRI) which gives a detailed picture with very high resolution (~0.5 mm) without the need to cut out samples and thereby destroy the geometry of the gel. One of the drawbacks for MRI-gels is that inhomogeneities in the magnetic field make it difficult to calibrate the gel in absolute values of absorbed dose. The Fe(II)/Fe(III) gel is the most well known of the gel dosimeters mentioned. The working principle is that it contains Fe(II)-ions that are oxidised to Fe(III)-ions when irradiated. The differences in paramagnetic properties between the ions can then be used to make an MRIimage of the dose distribution. The dose response is linear up to 40 Gy. The problem with this dosimeter type is the rapid diffusion of the Fe-ions which makes it necessary to image the gel immediately after irradiation to maintain the high resolution. In 1993 Maryanski et al. (Maryanski, 1993) reported a tissue-equivalent gel based on agarose, acrylamide and N,N´-methylene-bis-acrylamide (bis) in a de-aerated aqueous solution. The gel is called BANANA and works as a dosimeter due to the radiation induced polymerisation of the monomers acrylamide and bis. Later on, the agarose was replaced by gelatin because of its lower background signal. It is also more transparent which makes it easy to optically see the dose distribution since the polymerised gel volume changes to a white colour. This new gel is called BANG, and when further improved by substituting the acrylamide with acrylic acid it got the name BANG-2. The BANG-2 gel can measure doses down to 0.1 Gy which is much below the limit for both alanine gel and Fe(II/III) gel, but the dose response is only linear up to 6 Gy. Another drawback is the difficulties in preparing the gel. The preparation has to be made absolutely oxygen free since oxygen inhibits the polymerisation, and the gel must be stored in glass containers since most plastics are oxygen permeable. This puts great requirements on the preparation equipment, or the gel has to be bought, already cast in a predetermined shape. The glass container might also give some dosimetric effects since it has a higher atomic number than the gel itself. We have instead used a stiff agarose gel, heavily doped with alanine. The gel is heated and over saturated with alanine which recrystallizes when the gel is cooled down. When crystalline alanine is irradiated, radicals are formed which can be detected by means of electron spin resonance (ESR) spectroscopy. A signal proportional to the amount of radicals is then obtained. Since the amount of radicals is proportional to the absorbed dose, the substance may serve as a dosimeter material. The radicals in alanine are unusually stable because of the crystalline form, and in pure dry crystals the signal remains almost unchanged for several years. When the alanine is added to an agarose gel, the crystals are trapped in the gel which prevents signal diffusion. After irradiation, samples can be cut out at positions of interest. For the gel composition used in this work a sample weight of ~0.16 g is needed, which corresponds to a volume of ~0.12 cm3 (density: 1.28 g/ cm3). The shape of the sample can be chosen as convenient for the situation. The ESR analysis does not destroy the signal and thereby repeated read-outs of one sample are allowed. Alanine has a linear dose response from well below 1 Gy up to 104 Gy. The sensitivity when used in a gel allows doses down to ~3 Gy, as will be shown later on in this report. To make absolute dose measurements possible, as well as relative, the alanine/agarose gel requirescalibration. Absolute dose measurements are for example needed to verify Monte Carlo calculations experimentally. Dose planning systems used today do not take into account scattering effects at interfaces between materials of different atomic numbers, or scattering effects in a larger volume due to inserted shielding material. To verify that these simplifications do not set the outcome of the treatment at risk, and if possible to correct for the introduced errors, experimental measurements in such critical situations are needed. The aim of this report is to indicate a way of calibrating the alanine/agarose gel, and to examine the radical stability in the obtained calibration samples.
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| 5. |
- Olsson, Sara, et al.
(author)
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Dose response and fading characteristics of an Alanine-Agarose gel
- 1996
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In: Applied Radiation and Isotopes. - 0969-8043 .- 1872-9800. ; 47:11-12, s. 1211-1217
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Journal article (peer-reviewed)abstract
- The dose response of an alanine-agarose gel, analyzed by ESR spectrometry, and the stability of the radiation-induced free radicals have been investigated. The stability of the ESR signal is higher for dosimeter samples analyzed at 77 K than for dried samples, analyzed at room-temperature. The dose response is linear to within ±2% in the absorbed dose interval 2–100 Gy. The variations in spectral line shape were analyzed at temperatures between 77 and 270 K. The experimental ESR spectrum at 77 K was compared with a simulated spectrum of polycrystals of L-α-alanine.
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| 6. |
- Olsson, Sara, 1970-
(author)
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Free radical dosimetry employing ESR spectroscopy for clinical use
- 1998
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Licentiate thesis (other academic/artistic)abstract
- In all radiation therapy treatment it is important to thoroughly determine the absorbed dose in the tumour, in surrounding normal tissue and in risk organs. The dose distributions are usually calculated by means of computerised dose-planning systems. It is however necessary to compare the calculated dose distributions with experimental measurements.For measurements around brachytherapy sources, a tissue equivalent dosimeter material with a wide linear dose range and allowing a high spatial resolution, would be ideal because of the steep dose gradients around brachytherapy sources.These requirements can be met by free radical dosimetry (FRD), where the stable radiation induced radicals found in some crystalline substances can serve as a measure of the absorbed dose in the substance. The analysis is made by means of electron spin resonance (ESR) spectroscopy. The most common dosimeter material in FRD is the amino acid L-α-alanine.Various types of gel dosimeters are now being developed to obtain a three dimensional dosimeter where the gel is both dosimeter material and phantom material. The gel developed in this work is an alanine/agarose gel, where small alanine crystals are homogeneously distributed in the stiff agarose gel. The linear dose response of the alanine is not affected by the agarose gel, but the signal intensity and the stability of the radicals are somewhat lower because of the wet surroundings. In order to make measurements of the absorbed dose in absolute terms, the gel has been calibrated.Since a fine spatial resolution is crucial in brachytherapy measurements, a high sensitivity is needed. New dosimeter materials are tested to find a substance with the advantages of alanine but with higher sensitivity. Here the crystalline substance ammonium tartrate is presented. It is twice as sensitive as alanine, and by deuterating the crystals the sensitivity can be further increased by a factor of 1.6. The dose response is linear at least from 0.5 Gy to 4 kGy, and the energy dependence is even less than for alanine. We thus find ammonium tartrate promising for clinical use.
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| 7. |
- Wirestam, Ronnie, et al.
(author)
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Theoretical and experimental evaluation of phase-dispersion effects caused by brain motion in diffusion and perfusion MR imaging
- 1996
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In: Journal of Magnetic Resonance Imaging. - : Wiley. - 1522-2586 .- 1053-1807. ; 6:2, s. 348-355
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Journal article (peer-reviewed)abstract
- We investigated intravoxel phase dispersion caused by pulsatile brain motion in diffusion spin-echo pulse sequences. Mathematical models were used to describe the spatial and temporal velocity distributions of human brain motion. The spatial distribution of brain-tissue velocity introduces a phase spread over one voxel, leading to signal loss. This signal loss was estimated theoretically, and effects on observed diffusion coefficient and perfused capillary fraction were assessed. When parameters from a diffusion pulse sequence without motion compensation were used, and ECG triggering with inappropriate delay times was assumed, the maximal signal loss caused by brain-motion-induced phase dispersion was predicted to be 21%. This corresponds to a 95% overestimation of the diffusion coefficient, and the perfusion-fraction error was small. Corresponding calculations for motion-compensated pulse sequences predicted a 1% to 1.5% signal loss due to undesired phase dispersion, whereas experimental results indicated a signal loss related to brain motion of 4%.
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