1. |
- Alm, Jan, 1947-
(author)
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Dyslexia: Relevance of Concepts, Validity of Measurements, and Cognitive Functions
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The thesis opens with an exposition of different uses of the term dyslexia. In that context its conceptual relevance is discussed. The empirical studies investigate a) different aspects of validity of cognitive and achievement instruments often used in diagnostic assessment of dyslexia, b) different cognitive profiles for adults with dyslexia, and c) the relationship between cognitive and achievement measures.Study I demonstrated the factor structure of the Swedish WAIS-R to be in close agreement with results of comparable analyses on normal and clinical groups in many countries world-wide, giving strong support for the construct validity of the Swedish WAIS-R for a group of adults diagnosed with dyslexia. The results from the three-factor solution were interpreted in terms of theoretical constructs, notably those posited by Carroll (1993) and Horn (1989).The cognitive profiles of a sample of Swedish adults diagnosed with dyslexia—when using the three factors, the ACID profile, and the four-category Bannatyne profile—all resemble closely the profiles observed for a wide array of U.S. samples of children and adults diagnosed with dyslexia or learning disabilities. Gender differences on Digit Symbol, favoring females, were substantial in magnitude for the present sample, consistent with a bulk of research on gender differences for samples of normal individuals and of those identified with learning problems.In Study II, factor analysis of nine Swedish achievement tests often used for dyslexia assessment yielded five meaningful factors in a group of adults diagnosed with dyslexia. Factors appeared to measure decoding, visual speed, reading comprehension, reading fluency, and phonological ability. The relationship between the five achievement factors and WAIS-R variables was subsequently examined. The Visual Speed and Reading Comprehension factors each correlated significantly with four of six global WAIS-R scores (two of three IQs and two of three factor scores). Visual Speed tended to correlate significantly with nonverbal scores and Reading Comprehension with verbal scores. Although the Phonological Ability factor did not correlate significantly with any verbal or nonverbal global score, it did correlate significantly with the Freedom from Distractibility factor and with all its component subtests—Digit Span, Arithmetic, and Digit Symbol. Decoding (technical reading skill) showed no significant relationship to any WAIS-R variable studied. More surprisingly, the Reading Fluency factor failed to show significant relationships to the WAIS-R.Study III examined the validity of The Word Chain Test, a frequently used instrument in Swedish screening and diagnostic assessments of dyslexia. Different sources of validity evidence were evaluated. In summary, the results failed to support validity both for the WRI-index and the Wordchain subtest, suggesting that the instrument seems to be of questionable value in screening or diagnostic assessment of dyslexia.
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2. |
- Björnberg, Olof, et al.
(author)
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A Bifunctional dCTP Deaminase-dUTP Nucleotidohydrolase from the Hyperthermophilic Archaeon Methanocaldococcus jannaschii
- 2003
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In: Journal of Biological Chemistry. - 1083-351X. ; 278:23, s. 20667-20672
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Journal article (peer-reviewed)abstract
- By the sequential action of dCTP deaminase and dUTPase, dCTP is converted to dUMP, the precursor of thymidine nucleotides. In addition, dUTPase has an essential role as a safeguard against uracil incorporation in DNA. The putative dCTP deaminase (MJ0430) and dUTPase (MJ1102) from the hyperthermophilic archaeon Methanocaldococcus jannaschii were overproduced in Escherichia coli. Unexpectedly, we found the MJ0430 protein capable of both reactions, i.e. hydrolytic deamination of the cytosine ring and hydrolytic cleavage of the phosphoanhydride bond between the - and -phosphates. When the reaction was followed by thin layer chromatography using [3H]dCTP as substrate, dUMP and not dUTP was identified as a reaction product. In the presence of unlabeled dUTP, which acted as an inhibitor, no label was transferred from [3H]dCTP to the pool of dUTP. This finding strongly suggests that the two consecutive steps of the reaction are tightly coupled within the enzyme. The hitherto unknown bifunctionality of the MJ0430 protein appears beneficial for the cells because the toxic intermediate dUTP is never released. The MJ0430 protein also catalyzed the hydrolysis of dUTP to dUMP but with a low affinity for the substrate (Km >100 µM). According to limited proteolysis, the C-terminal residues constitute a flexible region. The other protein investigated, MJ1102, is a specific dUTPase with a Km for dUTP (0.4 µM) comparable in magnitude with that found for previously characterized dUTPases. Its physiological function is probably to degrade dUTP derived from other reactions in nucleotide metabolism.
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3. |
- Bröchner, Jan, 1948, et al.
(author)
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Outsourcing facilities services: needs and practices of Swedish owners of commercial property
- 2004
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In: Proceedings CIB W70 Facilities Management and Maintenance International Symposium, Hong Kong, 7-8 December 2004. ; , s. 395-400
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Conference paper (peer-reviewed)abstract
- Why and how facilities services are outsourced is a question that continues to attract interest. The purpose of this study has been to investigate links between categories of property owners and their demand for packaged facilities services. The empirical part is based on questionnaire responses from 20 large owners of commercial property in Sweden, and on interviews with 11 of these owners. Owners are characterized by portfolio value, geographical spread of properties, investment horizon, core business, and average tenant size. Three owner segments are identified and tentatively labelled Building Managers, Active Asset Managers, and Passive Asset Managers. Their outsourcing policies and practices differ clearly.
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4. |
- Carlomagno, F, et al.
(author)
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Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities.
- 2000
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In: International journal of cancer. Journal international du cancer. - 0020-7136. ; 85:6, s. 845-9
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Journal article (peer-reviewed)abstract
- In order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double-strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal-tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non-irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA-PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation- induced DSB repair. We also analysed the in vitro enzymatic activities, under non-irradiated conditions, of the DNA-PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA-PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro. The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients.
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5. |
- Hopewell, J W, et al.
(author)
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Time factor for acute tissue reactions following fractionated irradiation: a balance between repopulation and enhanced radiosensitivity.
- 2003
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In: International journal of radiation biology. - 0955-3002. ; 79:7, s. 513-24
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Journal article (peer-reviewed)abstract
- Experimental data for acute radiation-induced skin reactions are reviewed. These show that for dose fractionation schedules with gaps, repopulation is initiated after a lag period. After this lag period, the isoeffective dose for a given level of skin reaction first increases rapidly, but then slows. The timing of the lag period is related to the total turnover time of the tissue under investigation and, for example, is shorter in rodent skin than in pig or human skin. At the point when accelerated repopulation is initiated, there is a major shortening of the turnover time of the target cell population. At this time, there is evidence, for a short period, for an increase in radiosensitivity of the surviving stem cells in a number of acutely responding normal tissues. This effect is clearly illustrated by the results of experiments using sequential dose fractionation schedules. Prolongation of the schedule from 'short' to schedules that include irradiation over the period when the cell turnover is accelerated is associated with a marked increase in tissue radiosensitivity. Clinically, this is best illustrated by a comparison of the effects of accelerated fractionation schedules, involving multiple fractions/day, with daily fractionation schedules. The increase in radiosensitivity produced by the prolongation of the treatment from 2 to 4-5 weeks was equivalent to > or =1 Gy day(-1). Comparable findings were obtained from animal studies. In the oral mucosa of mice, the initiation of accelerated cell proliferation in surviving cells is associated with the loss of dose sparing by subsequent dose fractionation due to the loss of the capacity to repair sublethal damage. Studies in pig and human skin have indicated that increased radiosensitivity is associated with a loss of cells in the G1 phase of the cell cycle. A collation of these two sets of findings suggests that the repair of sublethal damage takes place over this phase of the cell cycle. One clinical implication of these findings is that the alpha/beta ratio for acute skin reaction changes with the length of the overall treatment time; it is approximately 4.0 Gy for 'short' fractionation schedules that avoid any shortening of the cell cycle time. This increases to 11.2-13.3 Gy for schedules given in 3-4 weeks and to approximately 35 Gy for schedules given in 5-6 weeks. Results for pig skin were in total agreement with those for human skin.
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7. |
- Qvarnström, Olov Fredrik, et al.
(author)
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DNA double strand break quantification in skin biopsies.
- 2004
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In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140. ; 72:3, s. 311-7
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Following induction of double strand breaks the histone H2AX is rapidly phosphorylated at regions flanking the breaks resulting in nuclear gamma H2AX foci. The purpose of this study was to use this endogenous signalling system to quantify the in vivo response to radiation in normal tissue. PATIENTS AND METHODS: Skin biopsies were taken from prostate cancer patients undergoing radiotherapy with a curative intent. Biopsies were taken at locations corresponding to 5 different doses in the range below 1.1 Gy per fraction. Biopsies were taken from patients 30 min following the first fraction and then once again following the fraction given after the first weekend break in the treatment course. The DNA double strand breaks were visualised as gamma H2AX foci using immunohistochemistry. Images were acquired using a CCD-camera and a fluorescence microscope and the gamma H2AX foci were quantified using digital image analysis including the basic procedures of top-hat transformation, threshold setting and labelling. RESULTS: Repeated assessments of the biopsies showed a high reproducibility in quantifying the number of foci per DNA area of the nucleated cells in epidermis. The reproducibility was equally good for the two biopsy occasions. A linear dose response was observed for the epidermis in the dose region 0-1 Gy. CONCLUSIONS: We have established a method to measure the relative amount of DNA double strand breaks by detecting gamma H2AX foci in patients exposed to radiotherapy. The method provides a tool to study induction and repair of DNA double strand breaks and has the potential to predict individual radiosensitivity.
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8. |
- Stalfors, Joacim, 1966, et al.
(author)
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Accuracy of tele-oncology compared with face-to-face consultation in head and neck cancer case conferences.
- 2001
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In: Journal of telemedicine and telecare. - 1357-633X. ; 7:6, s. 338-43
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Journal article (peer-reviewed)abstract
- Telemedicine was introduced for weekly tumour case conferences between Sahlgrenska University Hospital and two district hospitals in Sweden. The accuracy of tele-oncology was determined using simulated telemedicine consultations, in which all the material relating to each case was presented but without the patient in person. The people attending the conference were asked to determine the tumour ('TNM') classification and treatment. The patient was then presented in person, to give the audience the opportunity to ask questions and perform a physical examination. Then a new discussion regarding the tumour classification and the treatment plan took place, and the consensus was recorded. Of the 98 consecutive patients studied in this way, 80 could be evaluated by both techniques. Of these 80, 73 (91%) had the same classification and treatment plan in the telemedicine simulation as in the subsequent face-to-face consultation. In four cases the TNM classification was changed and for three patients the treatment plan was altered. The specialists also had to state their degree of confidence in the tele-oncology decisions. When they recorded uncertainty about their decision, it was generally because they wanted to palpate the tumour. In five of the seven patients with a different outcome, the clinical evaluation was stated to be dubious or not possible. The results show that telemedicine can be used safely for the management of head and neck cancers.
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9. |
- Turesson, I, et al.
(author)
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Normal tissue response to low doses of radiotherapy assessed by molecular markers--a study of skin in patients treated for prostate cancer.
- 2001
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In: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 40:8, s. 941-51
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate normal tissue response by molecular markers to multifraction low doses of ionizing radiation, with the focus on changes in repopulation, estimated using Ki-67 as the proliferation marker, and on expressions of the p53 and p21 proteins, identified as key proteins in the DNA damage checkpoint. Repeated skin biopsies were taken from patients treated for prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the keratinocytes in the basal cell layer of the epidermis were quantified immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given five times per week for seven weeks. The indices of the three markers were determined over the whole period. A significant suppression of the Ki-67 index was observed during the first weeks, followed by a significant gradual increase in the Ki-67 index over the last weeks. The p53 and p21 protein levels were almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21 index increased in a pattern very congruent to the Ki-67 index. In conclusion, daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in the basal layer, a cell growth arrest for a couple of weeks and a subsequent acceleration in repopulation during the following weeks of irradiation. The present findings also provided novel insights into the role of the p53/p21 pathway in the response of a normal epithelium to ionizing radiation as it is applied in radiotherapy.
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