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  • Huang, Ping, et al. (author)
  • Photo-induced oxidation of a dinuclear Mn-2(II,II) complex to the Mn-2(III,IV) state by inter- and intramolecular electron transfer to Ru-III tris-bipyridine
  • 2002
  • In: Journal of Inorganic Biochemistry. - 0162-0134 .- 1873-3344. ; 91:1, s. 159-172
  • Journal article (peer-reviewed)abstract
    • To model the structural and functional parts of the water oxidizing complex in Photosystem 11, a dimeric manganese(II,11) complex (1) was linked to a ruthenium(II)tris-bipyridine (Ru-II(bpy)3) complex via a substituted L-tyrosine, to form the trinuclear complex 2 [J. Inorg. Biochem. 78 (2000) 15]. Flash photolysis of 1 and Ru-II(bpy), in aqueous solution, in the presence of an electron acceptor, resulted in the stepwise extraction of three electrons by Ru-III(bpy), from the Mn-2(II,II) dimer, which then attained the Mn-2(III,IV) oxidation state. In a similar experiment with compound 2, the dinuclear Mn complex reduced the photo-oxidized Ru moiety via intramolecular electron transfer on each photochemical event. From EPR it was seen that 2 also reached the Mn-2(III,IV) state. Our data indicate that oxidation from the Mn-2(II,II) state proceeds stepwise via intermediate formation of Mn-2(II,III) and Mn-2(III,III). In the presence of water, cyclic voltammetry showed an additional anodic peak beyond Mn-2(II,III/III,III) oxidation which was significantly lower than in neat acetonitrile. Assuming that this peak is due to oxidation to Mn-2(III,IV), this suggests that water is essential for the formation of the Mn-2(III,IV) oxidation state. Compound 2 is a structural mimic of the water oxidizing complex, in that it links a Mn complex via a tyrosine to a highly oxidizing photosensitizer. Complex 2 also mimics mechanistic aspects of Photosystem 11, in that the electron transfer to the photosensitizer is fast and results in several electron extractions from the Mn moiety.
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  • Aapro, M, et al. (author)
  • Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel
  • 2008
  • In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 19:3, s. 420-432
  • Journal article (peer-reviewed)abstract
    • Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
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  • Abrahamsson, Christoffer, et al. (author)
  • Scatter correction of transmission near-infrared spectra by photon migration data: Quantitative analysis of solids
  • 2005
  • In: Applied Spectroscopy. - 1943-3530. ; 59:11, s. 1381-1387
  • Journal article (peer-reviewed)abstract
    • The scope of this work is a new methodology to correct conventional near-infrared (NIR) data for scattering effects. The technique aims at measuring the absorption coefficient of the samples rather than the total attenuation measured in conventional NIR spectroscopy. The main advantage of this is that the absorption coefficient is independent of the path length of the light inside the sample and therefore independent of the scattering effects. The method is based on time-resolved spectroscopy and modeling of light transport by diffusion theory. This provides an independent measure of the scattering properties of the samples and therefore of the path length of light. This yields a clear advantage over other preprocessing techniques, where scattering effects are estimated and corrected for by using the shape of the measured spectrum only. Partial least squares (PLS) calibration models show that, by using the proposed evaluation scheme, the predictive ability is improved by 50% as compared to a model based on conventional NIR data alone. The method also makes it possible to predict the concentration of active substance in samples with other physical properties than the samples included in the calibration model.
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  • Abrahamsson, M., et al. (author)
  • Changes of visual function and visual ability in daily life following cataract surgery
  • 2009
  • In: Acta Ophthalmologica Scandinavica. - : Blackwell Publishing. - 1395-3907 .- 1600-0420. ; 74:1, s. 69-73
  • Journal article (peer-reviewed)abstract
    • We conducted a prospective study of 56 patients aged 70 to 79 years undergoing cataract surgery, in order to determine the impact of surgery on subjective and objective measurements of visual ability. In 46 cases we could obtain all necessary data. Binocular visual acuity, near vision and contrast sensitivity improved due to surgery. Self-assessed ability to perform visually related tasks was examined in form of a questionnaire. The results show that there was no simple relationship between objective measurements and perceived visual ability. An impairment in preoperative visual acuity cannot be related to a specific loss of visual ability. In order to increase the quality of cataract surgery more subtly, subjective aspects of vision must be taken into consideration when operation is decided upon and in the evaluation of the results.
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  • Abrahamsson, M. L. A., et al. (author)
  • Ruthenium-manganese complexes for artificial photosynthesis : Factors controlling intramolecular electron transfer and excited-state quenching reactions
  • 2002
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 41:6, s. 1534-1544
  • Journal article (peer-reviewed)abstract
    • Continuing our work toward a system mimicking the electron-transfer steps from manganese to P-680(+) in photosystem II (PS II), we report a series of ruthenium(II)-manganese(II) complexes that display intramolecular electron transfer from manganese(II) to photooxidized ruthenium(III). The electron-transfer rate constant (k(ET)) values span a large range, 1 X 10(5)-2 x 10(7) s(-1), and we have investigated different factors that are responsible for the variation. The reorganization energies determined experimentally (lambda = 1.5-2.0 eV) are larger than expected for solvent reorganization in complexes of similar size in polar solvents (typically lambda approximate to 1.0 eV). This result indicates that the inner reorganization energy is relatively large and, consequently, that at moderate driving force values manganese complexes are not fast donors. Both the type of manganese ligand and the link between the two metals are shown to be of great importance to the electron-transfer rate. In contrast, we show that the quenching of the excited state of the ruthenium(II) moiety by manganese(II) in this series of complexes mainly depends on the distance between the metals. However, by synthetically modifying the sensitizer so that the lowest metal-to-ligand charge transfer state was localized on the nonbridging ruthenium(II) ligands, we could reduce the quenching rate constant in one complex by a factor of 700 without changing the bridging ligand. Still, the manganese(II)-ruthenium (III) electrontransfer rate constant was not reduced. Consequently, the modification resulted in a complex with very favorable properties.
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  • Abrahamsson, Putte, 1965, et al. (author)
  • Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
  • 2009
  • In: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
  • Journal article (peer-reviewed)abstract
    • AIMS: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. CONCLUSION: Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
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  • Abrahamsson, Thomas, et al. (author)
  • A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
  • 2009
  • In: in Allergy, vol 64. ; , s. 56-56
  • Conference paper (peer-reviewed)abstract
    • Background: Analyses of circulating chemokines offer novel tools to investigate the Th1/Th2 imbalance in allergic disease in vivo and explore the influence of pre- and postnatal factors in infancy. Objective: To relate circulating Th1- and Th2-associated chemokines to the development of allergic disease, pre- and postnatal factors and probiotic supplementation in infancy. Methods: Circulating levels of Th1-associated CXC-chemokine ligand (CXCL)9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17, CCL18 and CCL22 were assessed with Luminex and ELISA at birth (n=109), 6 (n=104), 12 (n=116) and 24 months (n=123) in 179 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding development of allergic disease and sensitization until two years of age. Results: The Th2-associated chemokines were as highest at birth and then decreased, whereas the Th1-associated chemokines increased with age. Low Th1- and high Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated CCL22 and reduced CXCL11 levels. High Th2-associated chemokine46 levels were associated with increased birth length and weight and long duration of breastfeeding, and high Th1-associated chemokine levels with day-care attendance. Presence of L. reuteri in stool the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months. Conclusion: Allergic disease in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels during the first year of life. The chemokine levels were affected by both pre and –postnatal factors.
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  • Berg, K. E., et al. (author)
  • Covalently linked ruthenium(II)-manganese(II) complexes : Distance dependence of quenching and electron transfer
  • 2001
  • In: European Journal of Inorganic Chemistry. - 1434-1948 .- 1099-1948. ; 2001:4, s. 1019-1029
  • Journal article (peer-reviewed)abstract
    • Continuing our development of artificial models for photosystem II in green plants, a series of compounds have been prepared in which a RU(bpy)(3)(2+) photosensitizer is covalently Linked to a manganese(II) electron donor. In addition to a trispicolylamine Ligand, two other manganese Ligands, dipicolylamine and aminodiacetic acid, have been introduced in order to study Ligands that are appropriate for the construction of manganese dimers with open coordination sites for the binding of water. Coordination equilibria of the manganese ions were monitored by EPR. The interactions between the ruthenium and manganese moieties were probed by flash photolysis, cyclic voltammetry and steady-state and time-resolved emission measurements. The quenching of the Ru-II excited state by Mn-II was found to be rapid in complexes with short Ru-Mn distances. Nevertheless, each Run species could be photo-oxidized by bimolecular quenching with methylviologen, and the subsequent electron transfer from Mn-II to Ru-III could be monitored.
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  • Brunner, M, et al. (author)
  • Ambient networks management challenges and approaches
  • 2004
  • In: MOBILITY AWARE TECHNOLOGIES AND APPLICATIONS, PROCEEDINGS. - BERLIN : SPRINGER. - 3540234233 ; , s. 196-216
  • Conference paper (peer-reviewed)abstract
    • System management addresses the provision of functions required for controlling, planning, allocating, monitoring, and deploying the resources of a network and of its services in order to optimize its efficiency and productivity and to safeguard its operation. It is also an enabler for the creation and sustenance of new business models and value chains, reflecting the different roles the service providers and users of a network can assume. Ambient Network represents a new networking approach and it aims to enable the cooperation of heterogeneous networks, on demand and transparently, to the potential users, without the need for pre-configuration or offline negotiation between network operators. To achieve these goals, ambient network management systems have to become dynamic, adaptive, autonomic and responsive to the network and its ambience. This paper discusses relationships between the concepts of autonomous and self-manageability and those of ambient networking, and the challenges and benefits that arise from their employment.
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  • Brunner, M, et al. (author)
  • Towards Ambient Networks Management
  • 2005
  • In: MOBILITY AWARE TECHNOLOGIES AND APPLICATIONS, PROCEEDINGS. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 3540294104 ; , s. 215-229
  • Conference paper (peer-reviewed)abstract
    • Ambient Networks (AN) are under development and they are based on novel networking concepts and systems that will enable a wide range of user and business communication scenarios beyond today's fixed, 3(rd) generation mobile and IP standards. Central to this project is the concept of Ambient Control Space (ACS) and the Domain Manager control function, which manages the underlying data transfer capabilities and presents a set of interfaces towards the supported services and applications. Network Management Systems of Ambient Networks must work in an environment where heterogeneous networks compose and cooperate, on demand and transparently, without the need for manual (pre or re)-configuration or offline negotiations between network operators. To achieve these goals, ambient network management systems must become dynamic, distributed, self-managing and responsive to the network and its ambience. This paper describes the different management research challenges and four complementary solution approaches (i.e. Pattern-based Management, Peer-to-Peer Management, (Un)PnP Management, Traffic Engineering Management Application Approaches) that enable efficient management of ambient networks, and the relationships between them, and presents the main results achieved so far.
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  • Carducci, Michael A., et al. (author)
  • A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer
  • 2007
  • In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 110:9, s. 1959-1966
  • Journal article (peer-reviewed)abstract
    • BACKGROUND. The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone- refractory prostate cancer (HRPC). METHODS. This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. RESULTS. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P =.136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P <.05 for each). The median time to BAP progression (> 50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P <.01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. CONCLUSIONS. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.
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  • Ek, Torben, 1963, et al. (author)
  • Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group
  • 2005
  • In: Pediatr Blood Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 44:5, s. 461-8
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The aim was to examine the immune reconstitution after current chemotherapy for childhood ALL, with a special focus on finding immunologic variables that predict a poor immune response to vaccinations. PROCEDURE: In a cross-sectional study of 31 children after treatment with the NOPHO ALL-1992 protocol peripheral blood lymphocyte subsets, T- and B-cell function in vitro and serum immunoglobulins (Ig) were measured. All patients were examined once, at 1 or at 6 months after cessation of chemotherapy, immediately before vaccination with DT and Hib. RESULTS: Lymphocytes, T-cells, and CD4+ T-cells were low at 6 months after treatment. Naive T-cell subsets were more reduced than memory subsets. In the high risk (HR) ALL group, CD8+ T-cells were reduced at 6 months. NK-cells were low at 1 month, but normal at 6 months; however, the CD3+CD56+ (NKT) subset was reduced at both time points. Total B-cell number was low at 1 month, but normal at 6 months. A relative increase of CD5+ B-cells (B-1 cells) was evident, particularly in the HR group. Antigen-independent T- and B-cell function in vitro were affected at 1 month, but virtually normalized at 6 months. Serum IgM level was decreased at 1 month and IgG3 level was increased at 1 and 6 months. CONCLUSIONS: This study shows that immune reconstitution after childhood ALL is slower than previously reported and emphasizes the influence of treatment intensity. The most intensively treated patients still have persistent abnormalities in T-, B-, and NK-cell subsets at 6 months post therapy and show a poor response to immunization with T-cell dependent antigens. In the HR group, routine re-immunizations before this time point are of limited benefit, and the effect of repeated vaccinations should be evaluated.
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  • Ekström, Jesper, et al. (author)
  • Bio-inspired, side-on attachment of a ruthenium photosensitizer to an iron hydrogenase active site model
  • 2006
  • In: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; :38, s. 4599-4606
  • Journal article (peer-reviewed)abstract
    • The first ruthenium - diiron complex [(mu- pdt) Fe-2(CO)(5){PPh2(C(6)H(4)CCbpy)} Ru(bpy)(2)](2+) 1 (pdt = propyldithiolate, bpy = 2,2'-bipyridine) is described in which the photoactive ruthenium trisbipyridyl unit is linked to a model of the iron hydrogenase active site by a ligand directly attached to one of the iron centers. Electrochemical and photophysical studies show that the light-induced MLCT excited state of the title complex is localized towards the potential diiron acceptor unit. However, the relatively mild potential required for the reduction of the acetylenic bipyridine together with the easily oxidized diiron portion leads to a reductive quenching of the excited state, instead. This process results in a transiently oxidized diiron unit which may explain the surprisingly high light sensitivity of complex 1.
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  • Frost, B.-M., et al. (author)
  • Vincristine in childhood leukaemia : No pharmacokinetic rationale for dose reduction in adolescents
  • 2003
  • In: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 92:5, s. 551-557
  • Journal article (peer-reviewed)abstract
    • Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day 1 of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m2 (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m 2 (137-1241) and total body clearance 362 ml/min/m2 (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002, ?-0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area > 1 m2, which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg. Conclusions: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered.
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  • Hedbäck, Gunilla, 1947, et al. (author)
  • The epidemiology of infantile hypertrophic pyloric stenosis in Sweden 1987-96.
  • 2001
  • In: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 85:5, s. 379-81
  • Journal article (peer-reviewed)abstract
    • To find out whether the incidence of infantile hypertrophic pyloric stenosis (IHPS) has changed over the past decade, and if so, to investigate possible contributory factors.All infants undergoing pyloromyotomy for IHPS in Sweden between 1987 and 1996 were studied. Using the national patient registers the yearly incidence was determined and evaluated in relation to sex, latitude, urbanisation, and type of surroundings by use of a Poisson model.There was a substantial decline from 2.7/1000 to 0.85/1000 over the time period. The incidence in the south was almost three times greater than in the north.The declining incidence and geographical difference suggest that environmental factors are of importance in this disorder.
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  • Johansson, A., et al. (author)
  • Synthesis and photophysics of one mononuclear Mn(III) and one dinuclear Mn(III,III) complex covalently linked to a ruthenium(II) tris(bipyridyl) complex
  • 2003
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 42, s. 7502-7511
  • Journal article (peer-reviewed)abstract
    • The preparation of donor (D)-photosensitizer (S) arrays, consisting of a manganese complex as D and a ruthenium tris(bipyridyl) complex as S has been pursued. Two new ruthenium complexes containing coordinating sites for one (2a) and two manganese ions (3a) were prepared in order to provide models for the donor side of photosystem II in green plants. The manganese coordinating site consists of bridging and terminal phenolate as well as terminal pyridyl ligands. The corresponding ruthenium-manganese complexes, a manganese monomer 2b and dimer 3b, were obtained. For the dimer 3b, our data suggest that intramolecular electron transfer from manganese to photogenerated ruthenium(III) is fast, k(ET) > 5 x 10(7) s(-1).
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  • Lie, S. O., et al. (author)
  • Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials
  • 2005
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 19:12, s. 2090-100
  • Journal article (peer-reviewed)abstract
    • In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.
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  • Magnuson, Ann, et al. (author)
  • High-valent Ruthenium-Manganese Complexes for Solar Energy Production.
  • 2001
  • In: PS2001 Proceedings.
  • Conference paper (peer-reviewed)abstract
    • We present progress in the development of artificial photosynthesis, as a means to harvesting and storage of solar energy. The plan is to compose molecular systems that combine known photochemistry with emerging functional model compounds. A photochemical device for solar energy conversion contains a photosensitizer, an electron acceptor system and a donor system that prevents charge recombination. Our goal is to utilize water as sacrificial electron donor, which will allow a net production of reducing equivalents, and the ultimate production of fuel. The only light-driven molecular catalyst for water oxidation exists in Photosystem II (PSII), which has a tetranuclear Mn-cluster in the active site. Here we present several Mn-compounds, that we have developed for the purpose of creating water-oxidizing catalysts. Our idea is to link Ru-tris(bipyridine) derivatives, which mimicks the function of the primary donor in PS II, with manganese complexes, mimicking the tetra-Mn cluster on the PSII donor side. We have constructed a number of heteronuclear complexes, containing a Ru-photosensitizer and various Mn-complexes. The compounds have been characterized with regards to their photophysical and photochemical properties, redox potentials and structure. The most promising compounds are capable of undergoing several electron transfers from the Mn-complex to the photosensitizer, leaving 3 to 4 oxidizing equivalents on the Mn. In the latest development, we have constructed ligands that stabilize higher oxidation states in Mn, in order to promote formation of Mn(V) which many believes is an intermediate in the water oxidation mechanism.
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  • Nakama, Leena H., et al. (author)
  • Effect of repetition rate on the formation of microtears in tendon in an in vivo cyclical loading model
  • 2007
  • In: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 25:9, s. 1176-1184
  • Journal article (peer-reviewed)abstract
    • We reported previously the formation of microtears in an in vivo loaded Flexor Digitorum Profundus (FDP) rabbit tendon with a repetition rate of 60 repetitions per minute and a peak force of 15% of maximum peak tetanic force for 80 cumulative hours. Tear area as a percent of tendon area, tear density (tears/mm(2)), and mean tear size (mu m(2)) were higher in tendons from the loaded limb compared to the unloaded control limb. The purpose of the present study was to compare those results to results obtained with a repetition rate of 10 while maintaining the same peak force and force-time integral (n = 8). Due to a strain gradient between the inner and outer sides of the FDP tendon, microtears were quantified in four regions, two regions each along the inner and outer sides of the tendon. The tear area as a percent of total tendon area and the mean tear size were significantly greater in the loaded limb compared to the unloaded limb (p < 0.03). However, the effects were less than those observed at 60 repetitions/min. The higher repetition loading pattern resulted in an increase in tear measures in all four regions, while the lower rate produced changes only in the outer regions of the tendon. This finding may establish where the initial sites of damage occur in tendons that insert into bone in a similar arrangement as the FDP. The results suggest that repetition rate or number of loading cycles is associated with increased tendon microtears or fragility in a dose-response pattern. (c) 2007 Orthopaedic Research Society.
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  • Nakama, L H, et al. (author)
  • Evidence of tendon microtears due to cyclical loading in an in vivo tendinopathy model
  • 2005
  • In: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 23:5, s. 1199-1205
  • Journal article (peer-reviewed)abstract
    • Tendon injuries at the epicondyle can occur in athletes and workers whose job functions involve repetitive, high force hand activities, but the early pathophysiologic changes of tendon are not well known. The purpose of this study was to evaluate early tendon structural changes, specifically the formation of microtears, caused by cyclical loading. The Flexor Digitorum Profundus (FDP) muscle of nine New Zealand White rabbits was stimulated to contract repetitively for 80 h of cumulative loading over 14 weeks. The contralateral limb served as a control, The tendon at the medial epicondyle insertion site was harvested, sectioned, and stained. Microtears were quantified, using image analysis software, in four regions of the tendon, two regions along the enthesis and two distal to the enthesis. The tear density (loaded: 1329 +/- 546 tears/mm(2); unloaded: 932 474 tears/mm(2)) and mean tear size (loaded: 18.3 +/- 6.1 mu m(2); unloaded: 14.0 +/- 4.8 mu m(2)) were significantly greater in the loaded limb (p < 0.0001) across all regions compared to the unloaded contralateral limb. These early microstructural changes in a repetitively loaded tendon may initiate a degenerative process that leads to tendinosis.
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43.
  • Nilsson, Johanna, 1984, et al. (author)
  • Evaluation of ionization techniques for mass spectrometric detection of contact allergenic hydroperoxides formed by autoxidation of fragrance terpenes.
  • 2008
  • In: Rapid communications in mass spectrometry : RCM. - : Wiley. - 0951-4198. ; 22:22, s. 3593-8
  • Journal article (peer-reviewed)abstract
    • Hydroperoxides formed by autoxidation of common fragrance terpenes are strong allergens and known to cause allergic contact dermatitis (ACD), a common skin disease caused by low molecular weight chemicals. Until now, no suitable methods for chemical analyses of monoterpene hydroperoxides have been available. Their thermolability prohibits the use of gas chromatography and their low UV-absorption properties do not promote sensitive analytical methods by liquid chromatography based on UV detection. In our study, we have investigated different liquid chromatography/mass spectrometry (LC/MS) ionization techniques, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI), for detection of hydroperoxides from linalool and limonene.Flow injection analysis was used to evaluate the three different techniques to ionize the monoterpene hydroperoxides, linalool hydroperoxide and limonene hydroperoxide, by estimating the signal efficacy under experimental conditions for positive and negative ionization modes. The intensities for the species [M+H](+) and [M+H-H(2)O](+) in positive ionization mode and [M-H](-) and [M-H-H(2)O](-) in negative ionization mode were monitored. It was demonstrated that the mobile phase composition and instrumental parameters have major influences on the ionization efficiency of these compounds. ESI and APCI were both found to be appropriate as ionization techniques for detection of the two hydroperoxides. However, APPI was less suitable as ionization technique for the investigated hydroperoxides. Copyright (c) 2008 John Wiley & Sons, Ltd.
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44.
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45.
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46.
  • Norgaard, B. L., et al. (author)
  • Long term risk stratification of patients with acute coronary syndromes: characteristics of troponin T testing and continuous ST segment monitoring
  • 2004
  • In: Heart. - 1468-201X. ; 90:7, s. 739-44
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To examine the long term prognostic characteristics of troponin T testing and continuous multi-lead ST segment monitoring in combination with clinical and 12 lead ECG risk indicators in patients with acute coronary syndromes (ACS). PATIENTS AND DESIGN: Patients with suspected ACS (n = 213) were studied. Troponin T was analysed in blood samples collected during the first 12 hours after admission. Continuous vectorcardiography ST segment monitoring was performed for 24 hours and the number of ST vector magnitude episodes was registered. Patients were followed up for a median of 28 months. The end point was a composite of cardiac death and acute myocardial infarction. RESULTS: Thirty eight (18%) patients reached the composite end point. The median (interquartile range) time from study inclusion to the time of the composite end point was longer for patients predicted to be at risk by troponin T testing (n = 27) than for those predicted to be at risk by ST segment monitoring (n = 20) (8.4 (0.2-15) months v 0.3 (0.1-4.3) months, p = 0.04). Significant univariate predictors of the composite end point were age > or = 65 years, diabetes, previous myocardial infarction, congestive heart failure, use of beta blockers or diuretics at admission, 12 lead ECG ST segment depression at admission, troponin T concentration > or = 0.10 microg/l, and > or = 1 ST vector magnitude episodes. Age > or = 65 years, previous myocardial infarction, and troponin T concentration > or = 0.10 microg/l provided independent prognostic information after multivariate analysis of potential risk variables. The prognostic value of transient ischaemic episodes in ACS seems to be confined to the short term. CONCLUSIONS: Both biochemical and continuous ECG markers reflect an increased risk for patients with ACS; however, the methods exhibit different temporal risk characteristics.
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47.
  • Ozturk, M., et al. (author)
  • Iron enrichment and photoreduction of iron under UV and PAR in the presence of hydroxycarboxylic acid : Implications for phytoplankton growth in the Southern Ocean
  • 2004
  • In: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645 .- 1879-0100. ; 51:22-24, s. 2841-2856
  • Journal article (peer-reviewed)abstract
    • Iron(III) photoreduction and the responses of phytoplankton under ultraviolet (UV) and photosynthetically available radiation (PAR) were investigated with the presence of hydroxycarboxylic acid (glucaric acid (GA), a model compound for organic acids excreted by phytoplankton). The incubation experiments were carried out on board using seawater samples collected in the location of the winter ice edge (WIE) and the spring ice edge (SIE) of the Southern Ocean. In this paper, we focus on the results of experiment in WIE. Throughout the experiments, dissolved Fe(II), major nutrients and in vivo fluorescence were monitored regularly. In addition, Chl-a, POC/PON, cell densities of phytoplankton and bacteria, bacterial production, organic peroxide, hydrogen peroxide and total CO2 were measured. The results from the WIE show that iron enrichment had a substantial effect on phytoplankton growth rate. Fe(III) addition in the presence of GA (FeGA) gave higher Fe(II) concentration and higher growth rate of phytoplankton than those in controls. Our results suggest that hydroxycarboxylic acid had a significant chemical and biological impact. The presence of GA influenced iron photochemistry and iron availability to phytoplankton. Phytoplankton growth responses to iron enrichments in incubations under UV and PAR were completely dissimilar. It seems that FeGA addition prominently changes the harmful effect of UV on the phytoplankton population. This study provides preliminary information on how the photoreduction of iron(III) and the phytoplankton growth are affected by iron enrichment in the presence of hydroxycarboxylic acid. © 2004 Elsevier Ltd. All rights reserved.
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48.
  • Persson, Eva M., et al. (author)
  • Is there an effect of food on the biliary secretion of cyclosporine and three in vivo formed metabolites in a porcine model?
  • 2007
  • In: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 253-258
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate the effect of lipids and P-glycoprotein (P-gp) inhibition on the biliary secretion of cyclosporine (CsA) and in vivo formed metabolites in pigs. A parallel group design including 12 pigs in four groups and a combined single-pass intestinal perfusion and bile collection method was employed. CsA was perfused through the jejunum in an isotonic fluid alone and with verapamil or lipids added. The study showed that there was no difference between the administration groups, except for the fraction of the absorbed dose that was excreted in bile was twice as high when CsA was administered together with lipids. In conclusion, CsA is excreted via the biliary route in pigs without any significant involvement of P-gp. Concomitant food-intake could increase the secretion to the bile, presumably by prolonged associations between the CsA and the lipid species.
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49.
  • Shih, Crystal, et al. (author)
  • Tryptophan-accelerated electron flow through proteins
  • 2008
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 320:5884, s. 1760-1762
  • Journal article (peer-reviewed)abstract
    • Energy flow in biological structures often requires submillisecond charge transport over long molecular distances. Kinetics modeling suggests that charge-transfer rates can be greatly enhanced by multistep electron tunneling in which redox-active amino acid side chains act as intermediate donors or acceptors. We report transient optical and infrared spectroscopic experiments that quantify the extent to which an intervening tryptophan residue can facilitate electron transfer between distant metal redox centers in a mutant Pseudomonas aeruginosa azurin. CuI oxidation by a photoexcited ReI-diimine at position 124 on a histidine(124)-glycine(123)-tryptophan(122)-methionine(121) β strand occurs in a few nanoseconds, fully two orders of magnitude faster than documented for single-step electron tunneling at a 19 angstrom donor-acceptor distance.
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50.
  • Sun, Licheng C., et al. (author)
  • Towards an artificial model for Photosystem II : a manganese(II,II) dimer covalently linked to ruthenium(II) tris-bipyridine via a tyrosine derivative
  • 2000
  • In: Journal of Inorganic Biochemistry. - 0162-0134 .- 1873-3344. ; 78:1, s. 15-22
  • Journal article (peer-reviewed)abstract
    • In order to model the individual electron transfer steps from the manganese cluster to the photooxidized sensitizer P-680(+) in Photosystem II (PS II) in green plants, the supramolecular complex 4 has been synthesized. In this complex, a ruthenium(II) tris-bipyridine type photosensitizer has been linked to a manganese(II) dimer via a substituted L-tyrosine, which bridges the manganese ions. The trinuclear complex 4 was characterized by electron paramagnetic resonance (EPR) and electrospray ionization mass spectrometry (ESI-MS). The excited state lifetime of the ruthenium tris-bipyridine moiety in 4 was found to be about 110 ns in acetonitrile, Using flash photolysis in the presence of an electron acceptor (methylviologen), it was demonstrated that in the supramolecular complex 4 an electron was transferred from the excited state of the ruthenium tris-bipyridine moiety to methylviologen, forming a methylviologen radical and a ruthenium(III) tris-bipyridine moiety. Next, the Ru(III) species retrieved the electron from the manganese(II/II) dimer in an intramolecular electron transfer reaction with a rate constant k(ET)>1.0X10(7) s(-1), generating a manganese(II/III) oxidation state and regenerating the ruthenium(II) photosensitizer. This is the first example of intramolecular electron transfer in a supramolecular complex, in which a manganese dimer is covalently linked to a photosensitizer via a tyrosine unit, in a process which mimics the electron transfer on the donor side of PS II.
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