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Search Results: 1 - 10 of 232388 matches for " Andrea C. Klaver "
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α-Synuclein and Anti-α-Synuclein Antibodies in Parkinson’s Disease, Atypical Parkinson Syndromes, REM Sleep Behavior Disorder, and Healthy Controls
Lynnae M. Smith, Mya C. Schiess, Mary P. Coffey, Andrea C. Klaver, David A. Loeffler
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052285
Abstract: α-synuclein is thought to play a key role in Parkinson’s disease (PD) because it is the major protein in Lewy bodies, and because its gene mutations, duplication, and triplication are associated with early-onset PD. There are conflicting reports as to whether serum and plasma concentrations of α-synuclein and anti-α-synuclein antibodies differ between PD and control subjects. The objectives of this study were to compare the levels of α-synuclein and its antibodies between individuals with typical PD (n = 14), atypical Parkinson syndromes (n = 11), idiopathic rapid eye movement sleep behavior disorder (n = 10), and healthy controls (n = 9), to assess the strength of association between these serum proteins, and to determine group sizes needed for a high probability (80% power) of detecting statistical significance for 25% or 50% differences between typical PD and control subjects for these measurements. Analysis of log-transformed data found no statistically significant differences between groups for either α-synuclein or its antibodies. The concentrations of these proteins were weakly correlated (Spearman rho = 0.16). In subjects with typical PD and atypical Parkinson syndromes, anti-α-synuclein antibody levels above 1.5 μg/ml were detected only in subjects with no more than four years of clinical disease. Power analysis indicated that 236 and 73 samples per group would be required for an 80% probability that 25% and 50% differences, respectively, in mean α-synuclein levels between typical PD and control subjects would be statistically significant; for anti-α-synuclein antibodies, 283 and 87 samples per group would be required. Our findings are consistent with those previous studies which suggested that serum concentrations of α-synuclein and its antibodies are not significantly altered in PD.
ELISA measurement of specific non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in sera from Alzheimer's disease, mild cognitively impaired, and noncognitively impaired subjects
Andrea C Klaver, Mary P Coffey, Lynnae M Smith, David A Bennett, John M Finke, Loan Dang, David A Loeffler
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-93
Abstract: Serum antibodies to Aβ1-42 monomer and soluble oligomers in AD, MCI, and NCI subjects (10/group) were measured by ELISA, subtracting polyvalent antibody binding and dissociating antibody-antigen complexes. Differences in mean antibody levels were assessed for significance with repeated measures ANOVA using restricted maximum likelihood estimation, using Tukey-Kramer tests and confidence intervals for multiple comparisons. Spearman's rank correlation was used to determine associations between anti-monomer and anti-oligomer antibody concentrations. Estimated sample sizes required to detect effects of various sizes were calculated.There were no significant differences between groups for mean anti-Aβ antibody levels, although these tended to be higher in AD than NCI specimens. Estimated group sizes of 328 and 150 for anti-Aβ monomer and oligomer antibodies, respectively, would have been required for 80% power for significance at 0.05 for a 25% increase in the AD mean relative to the NCI mean. Serum antibody concentrations to Aβ monomer and oligomers were strongly associated (correlations: 0.798 for undissociated sera, 0.564 for dissociated sera). Antibody-antigen dissociation significantly increased anti-Aβ monomer but not anti-Aβ oligomer antibody levels.The findings in this pilot study are consistent with relatively similar concentrations of specific, non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in AD, MCI, and NCI sera. The differences between groups for these antibodies would have required approximate group sizes of 328 and 150, respectively, for a high probability for statistical significance. These findings do not support the hypothesis that reduced levels of anti-Aβ antibodies might contribute to AD's pathogenesis.Amyloid-beta (Aβ), the major plaque-associated protein in the Alzheimer's disease (AD) brain, has become the main target for AD therapy since the formulation of the "amyloid hypothesis" [1]. The significance of serum antibodies t
Defect and solute properties in dilute Fe-Cr-Ni austenitic alloys from first principles
T. P. C. Klaver,D. J. Hepburn,G. J. Ackland
Physics , 2011, DOI: 10.1103/PhysRevB.85.174111
Abstract: We present results of an extensive set of first-principles density functional theory calculations of point defect formation, binding and clustering energies in austenitic Fe with dilute concentrations of Cr and Ni solutes.
First Principles Calculations of Defects in Unstable Crystals: Austenitic Iron
G. J. Ackland,T. P. C. Klaver,D. J. Hepburn
Physics , 2011,
Abstract: First principles calculations have given a new insight into the energies of point defects in many different materials, information which cannot be readily obtained from experiment. Most such calculation are done at zero Kelvin, with the assumption that finite temperature effects on defect energies and barriers are small. In some materials, however, the stable crystal structre of interest is mechanically unstable at 0K. In such cases, alternate approaches are needed. Here we present results of first principles calculations of austenitic iron using the VASP code. We determine an appropriate reference state for collinear magnetism to be the antiferromagnetic double-layer (AFM-d) which is both stable and lower in energy than other possible models for the low temperature limit of paramagnetic fcc iron. We then consider the energetics of dissolving typical alloying impurities (Ni, Cr) in the materials, and their interaction with point defects typical of the irradiated environment. We show that using standard methods there is a very strong dependence of calculated defect formation energies on the reference state chosen. Furthermore, there is a correlation between local free volume magnetism and energetics. The effect of substitutional Ni and Cr on defect properties is weak, rarely more than tenths of eV, so it is unlikely that small amounts of Ni and Cr will have a significant effect on the radiation damage in austenitic iron at high temperatures.
Ethnicity and thrombolysis in ischemic stroke: a hospital based study in Amsterdam
Jonathan M Coutinho, Eva C Klaver, Yvo B Roos, Jan Stam, Paul J Nederkoorn
BMC Neurology , 2011, DOI: 10.1186/1471-2377-11-81
Abstract: Retrospective single-centre study. Patients admitted with an ischemic stroke between 2003 and 2008 were included. Ethnicity was determined by self-identification and stratified into white and non-white (all other ethnicities). The main outcome measure was the difference in thrombolysis rate between white and non-white patients. Logistic regression analysis was used to identify potential confounders of the relation between ethnicity and thrombolysis.510 patients were included, 392 (77%) white and 118 (23%) non-white. Non-white patients were younger (median 69 vs. 60 years, p < 0.001), had a higher blood pressure at admission (median systolic 150 vs. 160 mmHg, p = 0.02) and a lower stroke severity (median NIHSS 5 vs. 4, p = 0.04). Non-white patients were significantly less often treated with thrombolysis compared to white patients (odds ratio 0.34, 95% CI 0.17-0.71), which was partly explained by a later arrival at the hospital. After adjustment for potential confounders (late arrival, age, blood pressure above upper limit for thrombolysis, and oral anticoagulation use), a trend towards a lower thrombolysis rate in non-whites remained (adjusted odds ratio 0.38, 95% CI 0.13 to 1.16).Non-white stroke patients less often received thrombolysis than white patients, partly as a result of a delay in presentation. In this single centre study, potential bias due to hospital differences or insurance status could be ruled out as a cause. The magnitude of the difference is worrisome and requires further investigation. Modifiable causes, such as patient delay, awareness of stroke symptoms, language barriers and treatment of cardiovascular risk factors, should be addressed specifically in these ethnic groups in future stroke campaigns.Despite its proven efficacy, only a minority of patients with an acute ischemic stroke are treated with intravenous thrombolysis [1-3]. A delay in hospital presentation is the most important reason why this treatment is withheld from stroke patients [
Measuring Semileptonic Asymmetries in LHCb
Suzanne Klaver,for the LHCb Collaboration
Physics , 2015,
Abstract: The $C\!P$-violating flavour-specific asymmetry in neutral $b$ mesons provides a method for testing the Standard Model. The measurements from the D0 experiment yield values of this asymmetry that disagree with the Standard Model at a level of 3.6 $\sigma$. This contribution discusses the latest LHCb measurements in this sector both from $B^0$ mesons ($a_{\mathrm{sl}}^d$) and $B^0_s$ mesons ($a_{\mathrm{sl}}^s$). Using their 2011 dataset, corresponding to an integrated luminosity of 1.0 $\mathrm{fb}^{-1}$ obtained in 2011, LHCb measured a value of $a_{\mathrm{sl}}^s = (-0.06 \pm 0.50_{\text{stat}} \pm 0.36_{\text{syst}}) \%$. Combining the 2011 and 2012 datasets, with an integrated luminosity of 3 $\mathrm{fb}^{-1}$, LHCb measured $a_{\mathrm{sl}}^d = (-0.02 \pm 0.19_{\text{stat}} \pm 0.30_{\text{syst}}) \%$. These are the most precise measurements of the parameters $a_{\mathrm{sl}}^s$ and $a_{\mathrm{sl}}^d$ to date. Plans for an updated result for $a_{\mathrm{sl}}^s$ using the full 3 $\mathrm{fb}^{-1}$ dataset are discussed. This will include new methods to determine detection asymmetries which are the dominating systematic uncertainty of the 2011 measurement.
Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice
Hao Cui, Amos C. Hung, David W. Klaver, Toshiharu Suzuki, Craig Freeman, Christian Narkowicz, Glenn A. Jacobson, David H. Small
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023007
Abstract: Background Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. Methodology/Principal Findings We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. Conclusions/Significance The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.
Mine Spoil Prairies Expand Critical Habitat for Endangered and Threatened Amphibian and Reptile Species
Michael J. Lannoo,Vanessa C. Kinney,Jennifer L. Heemeyer,Nathan J. Engbrecht,Alisa L. Gallant,Robert W. Klaver
Diversity , 2009, DOI: 10.3390/d1020118
Abstract: Coal extraction has been occurring in the Midwestern United States for over a century. Despite the pre-mining history of the landscape as woodlands, spent surface coalfields are often reclaimed to grasslands. We assessed amphibian and reptile species on a large tract of coal spoil prairie and found 13 species of amphibians (nine frog and four salamander species) and 19 species of reptiles (one lizard, five turtle, and 13 snake species). Two state-endangered and three state species of special concern were documented. The amphibian diversity at our study site was comparable to the diversity found at a large restored prairie situated 175 km north, within the historic prairie peninsula.
TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons
Robert J Gasperini, Xu Hou, Helena Parkington, Harry Coleman, David W Klaver, Adele J Vincent, Lisa C Foa, David H Small
Molecular Neurodegeneration , 2011, DOI: 10.1186/1750-1326-6-19
Abstract: Levels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Nav1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.These data suggest that activation of TRPM8 channels triggers the activation of Nav1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of Alzheimer's disease.Protein misfolding is a common feature of many neurodegenerative diseases. In some of these diseases, such as the synucleinopathies and the tauopathies, cytoplasmic proteins aggregate to form intracellular deposits. However, in the amyloidoses, which include Alzheimer's disease (AD), prion diseases and the British and Danish familial dementias, proteinaceous aggregates are observed extracellularly [1-4]. There is increasing evidence that the mechanism of neurotoxicity in these amyloidoses is similar and that it is the conformation of the aggregated protein, rather than its specific amino acid sequence which results in altered membrane permeability to calcium [5]. Therefore, studies on the mechanism of neurotoxicity in one disease may provide insights into the mechanisms involved in other
Surveillance as an Option for the Treatment of Small Renal Masses
S. Klaver,S. Joniau,H. Van Poppel
Advances in Urology , 2008, DOI: 10.1155/2008/705958
Abstract: Objectives. To review the natural history and biological potential of small renal masses in order to evaluate surveillance as a treatment option. Methods. Literature search of Medline and additional references from non-Medline-indexed publications concerning surveillance of small renal masses. Results. The natural history and biological potential of small renal masses can still not be unambiguously predicted at present. There seems to be no clear correlation between tumour size and presence of benign histology. The majority of small renal masses grow and the majority are cancer, but one cannot safely assume that a lack of growth on serial CT scans is the confirmation of absence of malignancy. Needle core biopsies could be used to help in decision making. They show a high accuracy for histopathological tumour type but are less accurate in evaluating Fuhrman grade. Conclusions. At present, surveillance of small renal masses should only be considered in elderly and/or infirm patients with competing health risks, in those with a limited life expectancy, and in those for whom minimal invasive treatment or surgery is not an option. In all other patients, active surveillance should only be considered in the context of a study protocol. Long-term, prospective studies are needed to provide a more accurate assessment of the natural history and metastastic potential of small renal masses.
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