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1.
  • Gyllenberg, A, et al. (författare)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
  • Tidskriftsartikel (refereegranskat)abstract
    • The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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  • Cuzick, Jack, et al. (författare)
  • Prevention and early detection of prostate cancer.
  • 2014
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:11, s. e484-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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  • Hamadani, Mehdi, et al. (författare)
  • Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation
  • 2014
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1729-1736
  • Tidskriftsartikel (refereegranskat)abstract
    • The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P < .001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
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  • McClune, Brian L., et al. (författare)
  • Allotransplantation for Patients Age >= 40 Years with Non-Hodgkin Lymphoma : Encouraging Progression-Free Survival
  • 2014
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:7, s. 960-968
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age >= 40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age >= 65; P = .0008). Fewer patients aged >= 65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age >= 65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age >= 65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age >= 55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age >= 55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.
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  • Sun, Chengjun, et al. (författare)
  • CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
  • 2012
  • Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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  • Uhlén, Fredrik, et al. (författare)
  • Damage investigation on tungsten and diamond diffractive optics at a hard x-ray free-electron laser
  • 2013
  • Ingår i: Optics Express. - : Optical Society America. - 1094-4087. ; 21:7, s. 8051-8061
  • Tidskriftsartikel (refereegranskat)abstract
    • Focusing hard x-ray free-electron laser radiation with extremely high fluence sets stringent demands on the x-ray optics. Any material placed in an intense x-ray beam is at risk of being damaged. Therefore, it is crucial to find the damage thresholds for focusing optics. In this paper we report experimental results of exposing tungsten and diamond diffractive optics to a prefocused 8.2 keV free-electron laser beam in order to find damage threshold fluence levels. Tungsten nanostructures were damaged at fluence levels above 500 mJ/cm(2). The damage was of mechanical character, caused by thermal stress variations. Diamond nanostructures were affected at a fluence of 59 000 mJ/cm(2). For fluence levels above this, a significant graphitization process was initiated. Scanning Electron Microscopy (SEM) and mu-Raman analysis were used to analyze exposed nanostructures.
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  • Uttervall, K., et al. (författare)
  • The Use of Novel Drugs Can Effectively Improve Response, Delay Relapse and Enhance Overall Survival in Multiple Myeloma Patients with Renal Impairment
  • 2014
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor. Aim: To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response. Methods: The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m(2). Result: The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients. Conclusion: High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.
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  • Aune, S, et al. (författare)
  • Improvement in the hospital organisation of CPR training and outcome after cardiac arrest in Sweden during a 10-year period
  • 2011
  • Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 82:4, s. 431-435
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim To describe (a) changes in the organisation of training in cardiopulmonary resuscitation (CPR) and the treatment of cardiac arrest in hospital in Sweden and (b) the clinical achievement, i.e. survival and cerebral function, among survivors after in-hospital cardiac arrest (IHCA) in Sweden. Methods Aspects of CPR training among health care providers (HCPs) and treatment of IHCA in Sweden were evaluated in 3 national surveys (1999, 2003 and 2008). Patients with IHCA are recorded in a National Register covering two thirds of Swedish hospitals. Results The proportion of hospitals with a CPR coordinator increased from 45% in 1999 to 93% in 2008. The majority of co-ordinators are nurses. The proportions of hospitals with local guidelines for acceptable delays from cardiac arrest to the start of CPR and defibrillation increased from 48% in 1999 to 88% in 2008. The proportion of hospitals using local defibrillation outside intensive care units prior to arrival of rescue team increased from 55% in 1999 to 86% in 2008. During the past 4 years in Sweden, survival to hospital discharge has been 29%. Among survivors, 93% have a cerebral performance category (CPC) score of I or II, indicating acceptable cerebral function. Conclusion During the last 10 years, there was a marked improvement in CPR training and treatment of IHCA in Sweden. During the past 4 years, survival after IHCA is high and the majority of survivors have acceptable cerebral function.
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  • Carlsson, Sigrid, 1982, et al. (författare)
  • No excess mortality after prostate biopsy: results from the European Randomized Study of Screening for Prostate Cancer.
  • 2011
  • Ingår i: BJU international. - 1464-410X. ; 107:12, s. 1912-1917
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Type - Harm (RCT)Level of Evidence1b OBJECTIVES: To assess possible excess mortality associated with prostate biopsy among screening participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC). SUBJECTS AND METHODS: From three centres in the ERSPC (Finland, The Netherlands and Sweden) 50194 screened men aged 50.2-78.4 years were prospectively followed. A cohort of 12959 first-time screening-positive men (i.e. with biopsy indication) was compared with another cohort of 37235 first-time screening-negative men. Overall mortality rates (i.e. other cause than prostate cancer mortality) were calculated and the 120-day and 1-year cumulative mortality were calculated by the Kaplan-Meier method, with a log-rank test for statistical significance. Incidence rate ratios (RR) and statistical significance were evaluated using Poisson regression analyses, adjusting for age, total PSA level, screening centre and whether a biopsy indication was present, or whether a biopsy was actually performed or not. RESULTS: There was no statistically significant difference in cumulative 120-day other cause mortality between the two groups of men: 0.24% (95% CI, 0.17-0.34) for screening-positive men vs 0.24% (95% CI, 0.20-0.30) for screening-negative men (P= 0.96). This implied no excess mortality for screening-positive men. Screening-positive men who were not biopsied (n= 1238) had a more than fourfold risk of other cause mortality during the first 120 days compared to screening-negative men: RR, 4.52 (95% CI, 2.63-7.74) (P < 0.001), adjusted for age, whereas men who were actually biopsied (n= 11721) had half the risk: RR, 0.41 (95% CI, 0.23-0.73) (P= 0.002), adjusted for age. Only 14/31 (45%) of the screening-positive men who died within 120 days were biopsied and none died as an obvious complication to the biopsy. CONCLUSIONS: Prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare.
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  • Carter, H Ballentine, et al. (författare)
  • Early detection of prostate cancer : AUA Guideline
  • 2013
  • Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 190:2, s. 419-426
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE:The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.MATERIALS AND METHODS:A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).RESULTS:Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.CONCLUSIONS:The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.
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  • Gamier, P., et al. (författare)
  • Deriving the characteristics of warm electrons (100-500 eV) in the magnetosphere of Saturn with the Cassini Langmuir probe
  • 2014
  • Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 104, s. 173-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Though Langmuir probes (LP) are designed to investigate cold plasma regions (e.g. ionospheres), a recent analysis revealed a strong sensitivity of the Cassini LP measurements to hundreds of eV electrons. These warm electrons impact the surface of the probe and generate a significant current of secondary electrons, that impacts both the DC level and the slope of the current-voltage curve of the LP (for negative potentials) through energetic contributions that may be modeled with a reasonable precision. We show here how to derive information about the incident warm electrons from the analysis of these energetic contributions, in the regions where the cold plasma component is small with an average temperature in the range similar to [100-500] eV. First, modeling the energetic contributions (based on the incident electron flux given by a single anode of the CAPS spectrometer) allows us to provide information about the pitch angle anisotropies of the incident hundreds of eV electrons. The modeling reveals indeed sometimes a large variability of the estimated maximum secondary electron yield (which is a constant for a surface material) needed to reproduce the observations. Such dispersions give evidence for strong pitch angle anisotropies of the incident electrons, and using a functional form of the pitch angle distribution even allows us to derive the real peak angle of the distribution. Second, rough estimates of the total electron temperature may be derived in the regions where the warm electrons are dominant and thus strongly influence the LP observations, i.e. when the average electron temperature is in the range similar to [100-500] eV. These regions may be identified from the LP observations through large positive values of the current-voltage slope at negative potentials. The estimated temperature may then be used to derive the electron density in the same region, with estimated densities between similar to 0.1 and a few particles/cm(3) (cc). The derived densities are in better agreement with the CAPS measurements than the values derived from the proxy technique (Morooka et al., 2009) based on the floating potential of the LP. Both the electron temperature and the density estimates lie outside the classical capabilities of the LP, which are essentially n(e) > 5 cc and T-e <5 eV at Saturn. This approximate derivation technique may be used in the regions where the cold plasma component is small with an average temperature in the range similar to [100-500] eV, which occurs often in the L range 6.4-9.4 R-S when Cassini is off the equator, but may occur anywhere in the magnetosphere. This technique may be all the more interesting since the CAPS instrument was shut down, and, though it cannot replace the CAPS instrument, the technique can provide useful information about the electron moments, with probably even better estimates than CAPS in some cases (when the plasma is strongly anisotropic). Finally, a simple modeling approach allows us to predict the impact of the energetic contributions on LP measurements in any plasma environment whose characteristics (density, temperature, etc.) are known. LP observations may thus be influenced by warm electrons in several planetary plasma regions in the solar system, and ambient magnetospheric electron density and temperature could be estimated in some of them (e.g. around several galilean satellites) through the use of Langmuir probes.
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  • Garnier, Philippe, et al. (författare)
  • The influence of the secondary electrons induced by energetic electrons impacting the Cassini Langmuir probe at Saturn
  • 2013
  • Ingår i: Journal of geophysical research Space Physics. - 2169-9402. ; 118:11, s. 7054-7073
  • Tidskriftsartikel (refereegranskat)abstract
    • The Cassini Langmuir Probe (LP) onboard the Radio and Plasma Wave Science experiment has provided much information about the Saturnian cold plasma environment since the Saturn Orbit Insertion in 2004. A recent analysis revealed that the LP is also sensitive to the energetic electrons (250–450 eV) for negative potentials. These electrons impact the surface of the probe and generate a current of secondary electrons, inducing an energetic contribution to the DC level of the current-voltage (I-V) curve measured by the LP. In this paper, we further investigated this influence of the energetic electrons and (1) showed how the secondary electrons impact not only the DC level but also the slope of the (I-V) curve with unexpected positive values of the slope, (2) explained how the slope of the (I-V) curve can be used to identify where the influence of the energetic electrons is strong, (3) showed that this influence may be interpreted in terms of the critical and anticritical temperatures concept detailed by Lai and Tautz (2008), thus providing the first observational evidence for the existence of the anticritical temperature, (4) derived estimations of the maximum secondary yield value for the LP surface without using laboratory measurements, and (5) showed how to model the energetic contributions to the DC level and slope of the (I-V) curve via several methods (empirically and theoretically). This work will allow, for the whole Cassini mission, to clean the measurements influenced by such electrons. Furthermore, the understanding of this influence may be used for other missions using Langmuir probes, such as the future missions Jupiter Icy Moons Explorer at Jupiter, BepiColombo at Mercury, Rosetta at the comet Churyumov-Gerasimenko, and even the probes onboard spacecrafts in the Earth magnetosphere.
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  • Holmberg, Lars, et al. (författare)
  • A comparison of prostate cancer survival in England, Norway and Sweden : A population-based study
  • 2012
  • Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 36:1, s. e7-e12
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The objective of the study was to compare patterns of survival 2001-2004 in prostate cancer patients from England, Norway and Sweden in relation to age and period of follow-up. Subjects and methods Excess mortality in men with prostate cancer was estimated using nation-wide cancer register data using a period approach for relative survival. 179,112 men in England, 23,192 in Norway and 59,697 in Sweden were included. Results In all age groups, England had the lowest survival, particularly so among men aged 80+. Overall age-standardised five-year survival was 76.4%, 80.3% and 83.0% for England, Norway and Sweden, respectively. The majority of the excess deaths in England were confined to the first year of follow-up. Conclusion The results indicate that a small but important group of older patients present at a late stage and succumb early to their cancers, possibly in combination with severe comorbidity, and this situation is more common in England than in Norway or Sweden.
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  • PÉREZ-SUÁREZ, I, et al. (författare)
  • LEPTIN RECEPTOR MOLECULAR VARIANTS ARE DIFFERENTLY REGULATED BY EXERCISE AND ENERGY DEFICIT IN HUMAN SKELETAL MUSCLE
  • 2014
  • Konferensbidrag (refereegranskat)abstract
    • IntroductionLeptin signals in skeletal muscles through pathways which share some steps with the insulin and IGF1. We have recently shown that LEPR (OBR-170) is increased in the dominant arm of tennis players 1 and is reduced in deltoid and vastus lateralis (VL) of obese compared to control subjects 2. The aim of this study was to determine whether exercise up-regulates the protein abundance and phosphorylation status of the different molecular variations of the LEPR (OBR-170, 128, 98A or 98B) in human skeletal muscle. We hypothesized that exercise will up-regulate leptin signaling in skeletal muscle. MethodsFifteen overweight men underwent three experimental phases: pre-test (PRE); caloric restriction (3.2 Kcal/kg body Wt/d) + exercise (45min unilateral arm cranking/d + 8h walking/d) for 4 days (CRE); and control isoenergetic diet + reduced exercise for 3 days (CD). During CRE, the diet consisted solely of whey protein (PRO, n=8) or sucrose (SU, n=7) (0.8 g/kg body Wt/d). Muscle biopsies (135 biopsies in all) were obtained from the trained and untrained deltoid, and VL, after 12h fast at PRE, and end of CRE and CD. The molecular variants of LEPR (OBR-170, 128, 98A and 98B) were determined by western blot and LEPR mRNA by PCR.  ResultsSerum leptin was reduced by ~60% following CRE and CD (P<0.05). LEPRs were more abundant in arm than leg muscles. LEPR mRNA was increased in exercised muscles after CRE. OBR-170 was reduced after CRE and CD only in the control arm (P<0.05). OBR-128 was increased after CD in exercised extremities (P<0.05). OBR-98A was increased after CRE in trained arm, and after CD in legs (P<0.05). However, OBR-98B was increased after CRE and CD in both arms and exercised extremities (P<0.05), being these effects more pronounced in the PRO group (P<0.05). After CD, LEPR mRNA returned to basal levels while LEPR expression was increased in all muscles (P<0.05). The fraction of LEPR activated (Tyr1141 phosphorylated) was reduced in arms but not in leg muscles. LEPR phosphorylation was correlated with JAK2 (upstream) and STAT3 (downstream) phosphorylation (r=0.67-0.89, P<0.05). DiscussionCaloric restriction seems to reduce the abundance of LEPR, but this effect varies depending on specific molecular variants of the receptor. The reduction of LEPR is partly counteracted by exercise, likely contributing to increase muscle leptin sensitivity. Whey protein ingestion facilitates these effects. Resuming normal food ingestion after a period of severe energy deficit is accompanied by increased expression LEPR in skeletal muscle. 
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  • Sperlich, B., et al. (författare)
  • Ergogenic effect of hyperoxic recovery in elite swimmers performing high-intensity intervals
  • 2011
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 21:6, s. e421-e429
  • Tidskriftsartikel (refereegranskat)abstract
    • This investigation tested the hypothesis that breathing oxygen-enriched air (FiO2=1.00) during recovery enhances peak (Ppeak) and mean power (Pmean) output during repeated high-intensity exercise. Twelve elite male swimmers (21 ± 3 years, 192.1 ± 5.9cm, 79.1 ± 8.2kg) inhaled either hyperoxic (HOX) or normoxic (NOX) air during 6-min recovery periods between five repetitions of high-intensity bench swimming, each involving 40 maximal armstrokes. Oxygen partial pressure (pO2) and saturation (SO2), [H+], pH, base excess and blood lactate concentration were measured before and after all intervals. The production of the reactive oxygen species (ROS) hydrogen peroxide was measured before, directly after and 15min after the test. Ppeak and Pmean with HOX recovery were significantly higher than with NOX throughout the third, fourth and fifth intervals (P<0.001-0.04). With HOX, electromyography activity was lower during the third, fourth and fifth intervals than during the first (P=0.05-0.001), with no such changes in NOX (P=0.99). There were no differences in blood lactate, pH, [H+] or base excess and ROS production at any time point with either HOX or NOX recovery. These findings demonstrate that the Ppeak and Pmean of elite swimmers performing high-intensity intervals can be improved by exposure to oxygen-enriched air during recovery. © 2011 John Wiley & Sons A/S.
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  • Andersson Trojer, Markus, 1981, et al. (författare)
  • Charged microcapsules for controlled release of hydrophobic actives. Part 1: encapsulation methodology and interfacial properties
  • 2013
  • Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 9:5, s. 1468-1477
  • Tidskriftsartikel (refereegranskat)abstract
    • Highly charged microcapsules have been prepared using the internal phase separation technique. The charges are introduced by using ionic dispersants, which have been characterized with respect to surface activity with a quartz crystal microbalance with dissipation monitoring and with optical tensiometry. The long-term stability of the microcapsule suspension without excess dispersant, as well as the stability at high ionic strength, have been investigated. Three types of ionic dispersants have been evaluated: a weak polyacid (poly(methacrylic acid)), a small set of ionic amphiphilic block copolymers of poly(methyl methacrylate)-block-poly(sodium (meth) acrylate) type and an oil-soluble anionic surfactant, sodium 1,5-dioxo-1,5-bis(3,5,5-trimethylhexyloxy)-3-((3,5,5-trimethylhexyloxy)carbonyl)pentane-2-sulfonate, in combination with a water-soluble polycation, poly(diallyldimethylammonium chloride). The block copolymer based microcapsule suspension is characterized by a long-term stability, even at high ionic strength, provided by electrostatic and steric stabilization. The weak polyacid based microcapsule suspension is stable for a few weeks, after which aggregation starts due to desorption of the dispersant. The surfactant-polycation based microcapsules appear to have a multicore morphology in contrast to the weak polyacid or block copolymer based microcapsules, which are core-shell particles.
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38.
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39.
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40.
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41.
  • Bill-Axelson, Anna, et al. (författare)
  • Radical prostatectomy versus watchful waiting in early prostate cancer.
  • 2011
  • Ingår i: The New England journal of medicine. - : Massachussetts Medical Society. - 1533-4406 .- 0028-4793. ; 364:18, s. 1708-17
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.
  •  
42.
  • Blom, Anna, et al. (författare)
  • A novel method for direct measurement of complement convertases activity in human serum.
  • 2014
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 178:1, s. 142-153
  • Tidskriftsartikel (refereegranskat)abstract
    • Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function directly or indirectly leads to pathologic conditions including higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases and ischemia-reperfusion injury. An assay for direct measurement of activity of the convertases in patient sera is not available. Existing assays testing convertase function are based on purified complement components and thus, convertase formation occurs under non-physiological conditions. We designed a new assay, in which C5 blocking compounds enabled separation of the complement cascade into two phases: the first ending at the stage of C5 convertases and the second ending with membrane attack complex formation. Use of rabbit erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for convertase formation enabled easy readout based on measurement of hemolysis. Thus, properties of patient sera could be studied directly regarding convertase activity and membrane attack complex formation. Another advantage of this assay was the possibility to screen for host factors such as C3 nephritic factor and other anti-complement autoantibodies, or gain-of-function mutations, which prolong half-live of complement convertases. Herein, we present proof of concept, detailed description and validation of this novel assay.
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43.
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44.
  • Bordes, Romain, 1981, et al. (författare)
  • Adsorption of Dianionic Surfactants Based on Amino Acids at Different Surfaces Studied by QCM-D and SPR
  • 2010
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 26:13, s. 10935-10942
  • Tidskriftsartikel (refereegranskat)abstract
    • The adsorption of three dicarboxylic amino acid-based surfactants, disodium N-lauroylaminomalonate, disodium N-lauroylaspartate, and disodium N-lauroylglutamate, has been studied by surface plasmon resonance (SPR) and the quartz crystal microbalance with dissipation monitoring (QCM-D). These surfactants have high cmc values, which means that the unimer concentration is high at the plateau value of adsorption. This gives rise to a considerable "bulk effect", which must be deducted from the observed value in order to obtain the true value of the adsorbed amount. In this article, we show how this can be done for the QCM-D technique. Adsorption is studied on silica, gold, gold hydrophobized by a self-assembled layer of an alkane thiol, and hydroxyapatite. Adsorption on hydroxyapatite differs very much among the three surfactants, with the aspartate derivative giving the strongest and the glutamate giving the weakest adsorption. This difference is explained as the difference in ability of the dicarboxylic amphiphiles to chelate calcium in the crystal lattice.
  •  
45.
  • Bordes, Romain, 1981, et al. (författare)
  • Role of an amide bond for self-assembly of surfactants
  • 2010
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 26:5, s. 3077-3083
  • Tidskriftsartikel (refereegranskat)abstract
    • Self-assembly in Solution and adsorption at the air-water interface and at Solid Surfaces were investigated for two amino-acid-based surfactants with conductimetry, NMR, tensiometry, quartz crystal microbalance with monitoring or the dissipation (QCM-D), and surface plasmon resonance (SPR). The surfactants studied were sodium N-lauroylglycinate and sodium N-lauroylsarcosinate, differing only in a methyl group on the amide nitrogen for the sarcosinate. Thus, the glycinate but not the surfactant is capable of forming intermolecular hydrogen bonds via the amide group. It was found that the amide bond, N-methylated or not, gave a substantial contribution to the hydrophilicity of the amphiphile. The ability to form intermolecular hydrogen bonds led to tighter packing at the air-water interface and ill a hydrophobic surface. It also increased the tendency for precipitation as all acid-soap pair oil addition of acid. Adsorption of the surfactants at a gold surface Was also investigated and gave unexpected results. The sarcosine-based surfactant seemed to give bilayer adsorption, while the glycine derivative adsorbed as a monolayer.
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46.
  • Born, D. -P, et al. (författare)
  • Hitze, Kälte und Höhenexposition im Fuβball : Adaptive Mechanismen und Verhaltensstrategien in variierenden Umweltbedingungen
  • 2014
  • Ingår i: Sportverletzung, Sportschaden. - : Georg Thieme Verlag KG. - 0932-0555 .- 1439-1236. ; 28:1, s. 17-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Football is played worldwide and players often have to cope with hot and cold temperatures as well as high altitude conditions. The upcoming and past world championships in Brazil, Qatar and South Africa illustrate the necessity for behavioural strategies and adaptation to extreme environmental conditions. When playing football in the heat or cold, special clothing, hydration and nutritional and acclimatisation strategies are vital for high-level performance. When playing at high altitude, the reduced oxygen partial pressure impairs endurance performance and alters the technical and tactical requirements. Special high-altitude adaptation and preparation strategies are essential for football teams based at sea-level in order to perform well and compete successfully. Therefore, the aim of the underlying review is: 1) to highlight the difficulties and needs of football teams competing in extreme environmental conditions, 2) to summarise the thermoregulatory, physiological, neuronal and psychological mechanism, and 3) to provide recommendations for coping with extreme environmental conditions in order to perform at a high level when playing football in the heat, cold and at high altitude.
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47.
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48.
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49.
  • Cheng, Arthur J., et al. (författare)
  • Doublet discharge stimulation increases sarcoplasmic reticulum Ca2+ release and improves performance during fatiguing contractions in mouse muscle fibres
  • 2013
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 591:15, s. 3739-3748
  • Tidskriftsartikel (refereegranskat)abstract
    • Double discharges (doublets) of motor neurones at the onset of contractions increase both force and rate of force development during voluntary submaximal contractions. The purpose of this study was to examine the role of doublet discharges on force and myoplasmic free [Ca2+] ([Ca2+](i)) during repeated fatiguing contractions, using a stimulation protocol mimicking the in vivo activation pattern during running. Individual intact fibres from the flexor digitorum brevis muscle of mice were stimulated at 33 degrees C to undergo 150 constant-frequency (five pulses at 70 Hz) or doublet (an initial, extra pulse at 200 Hz) contractions at 300 ms intervals. In the unfatigued state, doublet stimulation resulted in a transient (approximate to 10 ms) approximate doubling of [Ca2+](i), which was accompanied by a greater force-time integral (approximate to 70%) and peak force (approximate to 40%) compared to constant frequency contractions. Moreover, doublets markedly increased force-time integral and peak force during the first 25 contractions of the fatiguing stimulation. In later stages of fatigue, addition of doublets increased force production but the increase in force production corresponded to only a minor portion of the fatigue-induced reduction in force. In conclusion, double discharges at the onset of contractions effectively increase force production, especially in early stages of fatigue. This beneficial effect occurs without additional force loss in later stages of fatigue, indicating that the additional energy cost induced by doublet discharges to skeletal muscle is limited.
  •  
50.
  • Cheng, J., et al. (författare)
  • One-pot synthesis of porous gold nanoparticles by preparation of Ag/Au nanoparticles followed by dealloying
  • 2013
  • Ingår i: Colloids and Surfaces A: Physicochemical and Engineering Aspects. - : Elsevier BV. - 1873-4359 .- 0927-7757. ; 436, s. 823-829
  • Tidskriftsartikel (refereegranskat)abstract
    • Porous gold nanoparticles were obtained from nanoparticle alloys of gold and silver. The alloy nanoparticles were prepared by reducing the gold and silver precursors, HAuCl4 and AgNO3, respectively with NaBH4. The reduction was made in a microemulsion of water-in-oil type and the precursors were contained in the water droplets. The droplet size of the microemulsion was 25-30 nm and the size of the mixed nanoparticles was 5-7 nm. The position of the plasmon band in the absorption spectrum, as well as analysis by energy-dispersive X-ray spectroscopy linked to high resolution scanning transmission electron microscopy showed that the nanoparticles were true alloys, not of core-shell type. The mixed nanoparticles were subsequently dealloyed by treatment with nitric acid, which dissolved silver much more readily than gold.
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