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- Bellini, Rosalba, et al.
(author)
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Conformational Preferences of a Tropos Biphenyl Phosphinooxazoline-a Ligand with Wide Substrate Scope
- 2016
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In: Acs Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 6:3, s. 1701-1712
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Journal article (peer-reviewed)abstract
- Excellent enantioselectivities are observed in palladium-catalyzed allylic substitutions of a wide range of substrate types and nucleophiles using a bidentate ligand composed of oxazoline and chirally flexible biaryl phosphite elements. This unusually wide substrate scope is shown by experimental and theoretical studies of its eta(3)-allyl and eta(2)-olefin complexes not to be a result of configurational interconversion of the biaryl unit, since the ligand in all reactions adopts an S-a,S configuration on coordination to palladium, but rather the ability of the ligand to adapt the size of the substrate-binding pocket to the reacting substrate. This ability also serves as an explanation to its excellent performance in other types of catalytic processes.
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| 2. |
- Damber, Jan-Erik, 1949, et al.
(author)
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The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin
- 2006
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In: Cancer Chemother Pharmacol. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 58:3, s. 354-360
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Journal article (peer-reviewed)abstract
- Background: Tumour growth is dependent on angiogenesis. Antiangiogenic chemotherapy, i.e. continuous or metronomic low-dose chemotherapy, is a method for administrating cytostatics at a low and well-tolerated concentration without prolonged breaks. The target is the genetically stable endothelial cells playing a pivotal role in angiogenesis within the tumour. Different mediators could mediate the antiangiogenic effect of metronomic chemotherapy. One of these mediators could be thrombospondin (TSP). TSP is a potent inhibitor of angiogenesis and might therefore be important in controlling tumour growth. This study was designed to evaluate the effects of low-dose continuous or moderate-dose bolus chemotherapy on tumour growth and on tumour expression of TSP. Materials and methods: Rats bearing a malignant prostate tumour (Dunning AT-1) not expressing TSP were treated systemically with cyclophosphamide, doxorubicin or paclitaxel and the combination of cyclophosphamide and doxorubicin. Tumour growth and body weight were measured during the treatment. CD36, one of TSP’s main receptors, was also analysed. The expression pattern of TSP-1, TSP-2 and CD36 was investigated using immunohistochemistry and Western blot analyses. Q-PCR was used to analyse TSP-1 mRNA expression. Results: Low-dose cyclophosphamide and paclitaxel re-induced the expression of TSP in the tumours. However, following a bolus dose of doxorubicin, tumours showed no expression of TSP. Both cyclophosphamide and doxorubicin treatments decreased the tumour weight by more than 60% compared with vehicle controls. When cyclophosphamide and doxorubicin were combined the tumour weight was reduced by 47%, while paclitaxel reduced the tumour weight by 18% compared to the vehicle controls. Conclusions: Systemic low-dose continuous treatment of a rat prostate cancer model with cyclophosphamide and paclitaxel induced the expression of TSP in tumour tissue and inhibited tumour growth. These findings support the hypothesis that the anti-tumour effect of low-dose metronomic chemotherapy, at least with certain chemotherapeutics, is partly mediated by induction of endogenous antiangiogenic factors.
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| 5. |
- Engvall, Karin, et al.
(author)
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Ocular, nasal, dermal and respiratory symptoms in relation to heating, ventilation, energy conservation and reconstruction of older multi-family houses
- 2003
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In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 13:3, s. 206-211
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Journal article (peer-reviewed)abstract
- The aim was to study relationships between symptoms compatible with the sick building syndrome, type of heating and ventilation system, energy saving, and reconstruction in older dwellings. In Stockholm, 4815 inhabitants in 231 multi-family buildings built before 1961 were randomly selected, of whom 3241 participated (77%). Symptoms and personal factors were assessed by a postal questionnaire. Independent information on building characteristics, and energy saving measures was gathered from the building owners. Multiple logistic regression analysis was applied to calculate odds ratios (OR) adjusting for age, gender, hay fever, current smoking, population density, type of ventilation, type of heating system, and ownership of the building. Subjects in buildings with a mechanical ventilation system had less ocular and nasal symptoms (OR = 0.29-0.85). Heating by electric radiators, and wood heating was associated with an increase of most symptoms (OR = 1.18-1.74). In total, 48% lived in buildings that had gone through at least one type of reconstruction or energy saving remedies during the latest 10 years, including exchange of heating or ventilation system, and sealing measures (exchange of windows, sealing of window frames, roof/attic insulation, and phasade insulation). Energy saving was associated with both a decrease and increase of different symptoms. Major reconstruction of the interior of the building was associated with an increase of most symptoms (OR = 1.09-1.90), and buildings with more than one sealing measure had an increase of ocular, nasal symptoms, headache and tiredness (OR = 1.22-2.49). In conclusion, major reconstruction of the interior, direct heated electric radiators, wood heating, and multiple sealing of buildings were associated with an increase of some symptoms. The study supports the view that mechanical ventilation in dwellings is beneficial from a health point of view.
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| 7. |
- Engvall, Karin, et al.
(author)
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The Stockholm Indoor Environment Questionnaire (SIEQ) : A sociological based tool for assessment of indoor environment and health in dwellings
- 2004
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In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 14:1, s. 24-33
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Journal article (peer-reviewed)abstract
- The aim was to develop and validate a standardized questionnaire - the Stockholm Indoor Environment Questionnaire (SIEQ). The validation procedure was based on sociological principles and test procedures for validation. The indicators of indoor environment are air quality, thermal climate, noise, and illumination. The indicators of health are symptoms comprised in the sick building syndrome (SBS). The questionnaire also contains questions about the apartment, individual behavior, and personal factors. The everyday language describing the building and its function was first obtained by qualitative personal interviews, then by standardized questions. The interview questionnaire was transformed into a postal self-administered questionnaire. The reduction of the questionnaire was based on correlation analysis. It was found that to obtain a good validity, general questions are not sufficient, but specific question on perceptions and observations are needed. Good test-retest agreement was found both on an area level, building level, and individually. For each indicator, a set of questions are constructed and validated. SIEQ has been used in several studies, and the results are presented in graphic problem profiles. Reference data has been calculated for the Stockholm area.
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| 9. |
- Falhammar, Henrik, et al.
(author)
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Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency : a Swedish population-based national cohort study
- 2015
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In: The Journal of Clinical Endocrinology & Metabolism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-972X. ; 100:9, s. 3520-3528
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Journal article (peer-reviewed)abstract
- CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. OBJECTIVE: This study aimed to study cardiovascular and metabolic morbidity in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. MAIN OUTCOME MEASURES: To study cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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| 10. |
- Falhammar, Henrik, et al.
(author)
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Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- 2014
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In: The Journal of Clinical Endocrinology & Metabolism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-972X .- 1945-7197.
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Journal article (peer-reviewed)abstract
- Context: Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. Objective: To study mortality and causes of death in CAH. Design, Setting and Participants: We studied patients with CAH (21-hydroxylase deficiency, n=588; CYP21A2 mutations known, >80%), and compared them with controls (n=58800). Data were derived through linkage of national population-based registers. Main Outcome Measures: Mortality and causes of death. Results: The mean age of death was 41.2±26.9 years in CAH patients and 47.7±27.7 years in controls (P<0.001). Among CAH patients 23 (3.9%) had deceased compared to 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3(1.2-4.3) in CAH males and 3.5(2.0-6.0) in CAH females. Including only patients born 1952-2009, gave similar total results but only patients with salt-wasting or with unclear phenotype had an increased mortality. The causes of death in CAH patients were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter all except one were deceased before the introduction of neonatal screening in 1986 and most of them in the first weeks of life, probably in an adrenal crisis. Conclusions: CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The salt-wasting phenotype seemed to have worse outcome also in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.
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