共查询到20条相似文献,搜索用时 31 毫秒
1.
High-Resolution Mechanical Imaging of Glioblastoma by Multifrequency Magnetic Resonance Elastography
Kaspar-Josche Streitberger Martin Reiss-Zimmermann Florian Baptist Freimann Simon Bayerl Jing Guo Felix Arlt Jens Wuerfel Jürgen Braun Karl-Titus Hoffmann Ingolf Sack 《PloS one》2014,9(10)
Objective
To generate high-resolution maps of the viscoelastic properties of human brain parenchyma for presurgical quantitative assessment in glioblastoma (GB).Methods
Twenty-two GB patients underwent routine presurgical work-up supplemented by additional multifrequency magnetic resonance elastography. Two three-dimensional viscoelastic parameter maps, magnitude |G*|, and phase angle φ of the complex shear modulus were reconstructed by inversion of full wave field data in 2-mm isotropic resolution at seven harmonic drive frequencies ranging from 30 to 60 Hz.Results
Mechanical brain maps confirmed that GB are composed of stiff and soft compartments, resulting in high intratumor heterogeneity. GB could be easily differentiated from healthy reference tissue by their reduced viscous behavior quantified by φ (0.37±0.08 vs. 0.58±0.07). |G*|, which in solids more relates to the material''s stiffness, was significantly reduced in GB with a mean value of 1.32±0.26 kPa compared to 1.54±0.27 kPa in healthy tissue (P = 0.001). However, some GB (5 of 22) showed increased stiffness.Conclusion
GB are generally less viscous and softer than healthy brain parenchyma. Unrelated to the morphology-based contrast of standard magnetic resonance imaging, elastography provides an entirely new neuroradiological marker and contrast related to the biomechanical properties of tumors. 相似文献2.
BackgroundPathologies of the muscles can manifest different physiological and functional changes. To adapt treatment, it is necessary to characterize the elastic property (shear modulus) of single muscles. Previous studies have used magnetic resonance elastography (MRE), a technique based on MRI technology, to analyze the mechanical behavior of healthy and pathological muscles. The purpose of this study was to develop protocols using MRE to determine the shear modulus of nine thigh muscles at rest.MethodsTwenty-nine healthy volunteers (mean age = 26 ± 3.41 years) with no muscle abnormalities underwent MRE tests (1.5 T MRI). Five MRE protocols were developed to quantify the shear moduli of the nine following thigh muscles at rest: rectus femoris (RF), vastus medialis (VM), vastus intermedius (VI), vastus lateralis (VL), sartorius (Sr), gracilis (Gr), semimembranosus (SM), semitendinosus (ST), and biceps (BC). In addition, the shear modulus of the subcutaneous adipose tissue was analyzed.ResultsThe gracilis, sartorius, and semitendinosus muscles revealed a significantly higher shear modulus (μ_Gr = 6.15 ± 0.45 kPa, μ_ Sr = 5.15 ± 0.19 kPa, and μ_ ST = 5.32 ± 0.10 kPa, respectively) compared to other tissues (from μ_ RF = 3.91 ± 0.16 kPa to μ_VI = 4.23 ± 0.25 kPa). Subcutaneous adipose tissue had the lowest value (μ_adipose tissue = 3.04 ± 0.12 kPa) of all the tissues tested.ConclusionThe different elasticities measured between the tissues may be due to variations in the muscles'' physiological and architectural compositions. Thus, the present protocol could be applied to injured muscles to identify their behavior of elastic property. Previous studies on muscle pathology found that quantification of the shear modulus could be used as a clinical protocol to identify pathological muscles and to follow-up effects of treatments and therapies. These data could also be used for modelling purposes. 相似文献
3.
Working memory (WM) refers to the temporary storage and manipulation of information necessary for performance of complex cognitive tasks. There is a growing interest in whether and how propofol anesthesia inhibits WM function. The aim of this study is to investigate the possible inhibition mechanism of propofol anesthesia based on the functional connections of multi-local field potentials (LFPs) and behavior during WM tasks. Adult SD rats were randomly divided into 3 groups: pro group (0.5 mg·kg−1·min−1,2 h), PRO group (0.9 mg·kg−1·min−1, 2 h) and control group. The experimental data were 16-channel LFPs obtained at prefrontal cortex with implanted microelectrode array in SD rats during WM tasks in Y-maze at 24, 48, 72, 96, 120 hours (day 1-day 5) after propofol anesthesia, and the behavior results of WM were recoded at the same time. Directed transfer function (DTF) method was applied to analyze the connections among LFPs directly. Furthermore, the causal networks were identified by DTF. The clustering coefficient (C), network density (D) and global efficiency (Eglobal) were selected to describe the functional connectivity quantitatively. The results show that: comparing with the control group, the LFPs functional connectivity in pro group were no significantly difference (p>0.05); the connectivity in PRO group were significantly decreased (p<0.05 at 24 hours, p<0.05 at 48 hours), while no significant difference at 72, 96 and 120 hours for rats (p>0.05), which were consistent with the behavior results. These findings could lead to improved understanding the mechanism of inhibition of anesthesia on WM functions from the view of connections among LFPs. 相似文献
4.
Introduction
Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE) is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS) is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS.Methods
We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS.Results
In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001).Conclusions
Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation. 相似文献5.
Jan Seifert Christian M. Hammer Johannes Rheinlaender Saadettin Sel Michael Scholz Friedrich Paulsen Tilman E. Sch?ffer 《PloS one》2014,9(1)
Riboflavin/UVA-induced corneal collagen cross-linking has become an effective clinical application to treat keratoconus and other ectatic disorders of the cornea. Its beneficial effects are attributed to a marked stiffening of the unphysiologically weak stroma. Previous studies located the stiffening effect predominantly within the anterior cornea. In this study, we present an atomic force microscopy-derived analysis of the depth-dependent distribution of the Young''s modulus with a depth resolution of 5 µm in 8 cross-linked porcine corneas and 8 contralateral controls. Sagittal cryosections were fabricated from every specimen and subjected to force mapping. The mean stromal depth of the zone with effective cross-linking was found to be 219±67 µm. Within this cross-linked zone, the mean Young''s modulus declined from 49±18 kPa at the corneal surface to 46±17 kPa, 33±11 kPa, 17±5 kPa, 10±4 kPa and 10±4 kPa at stromal depth intervals of 0–50 µm, 50–100 µm, 100–150 µm, 150–200 µm and 200–250 µm, respectively. This corresponded to a stiffening by a factor of 8.1 (corneal surface), 7.6 (0–50 µm), 5.4 (50–100 µm), 3.0 (100–150 µm), 1.6 (150–200 µm), and 1.5 (200–250 µm), when compared to the Young''s modulus of the posterior 100 µm. The mean Young''s modulus within the cross-linked zone was 20±8 kPa (2.9-fold stiffening), while it was 11±4 kPa (1.7-fold stiffening) for the entire stroma. Both values were significantly distinct from the mean Young''s modulus obtained from the posterior 100 µm of the cross-linked corneas and from the contralateral controls. In conclusion, we were able to specify the depth-dependent distribution of the stiffening effect elicited by standard collagen cross-linking in porcine corneas. Apart from determining the depth of the zone with effective corneal cross-linking, we also developed a method that allows for atomic force microscopy-based measurements of gradients of Young''s modulus in soft tissues in general. 相似文献
6.
Two DCM mutants (E40K and E54K) of tropomyosin (Tm) were examined using the thin-filament extraction/reconstitution technique. The effects of the Ca2+, ATP, phosphate (Pi), and ADP concentrations on isometric tension and its transients were studied at 25°C, and the results were compared to those for the WT protein. Our results indicate that both E40K and E54K have a significantly lower T
HC (high Ca2+ tension at pCa 4.66) (E40K: 1.21±0.06 T
a, ±SEM, N = 34; E54K: 1.24±0.07 T
a, N = 28), a significantly lower T
LC (low- Ca2+ tension at pCa 7.0) (E40K: 0.07±0.02 T
a, N = 34; E54K: 0.06±0.02 T
a, N = 28), and a significantly lower T
act (Ca2+ activatable tension) (T
act = T
HC–TLC, E40K: 1.15±0.08 T
a, N = 34; E54K: 1.18±0.06 T
a, N = 28) than WT (T
HC = 1.53±0.07 T
a, T
LC = 0.12±0.01 T
a, T
act = 1.40±0.07 T
a, N = 25). All tensions were normalized to T
a ( = 13.9±0.8 kPa, N = 57), the tension of actin-filament reconstituted cardiac fibers (myocardium) under the standard activating conditions. The Ca2+ sensitivity (pCa50) of E40K (5.23±0.02, N = 34) and E54K (5.24±0.03, N = 28) was similar to that of the WT protein (5.26±0.03, N = 25). The cooperativity increased significantly in E54K (3.73±0.25, N = 28) compared to WT (2.80±0.17, N = 25). Seven kinetic constants were deduced using sinusoidal analysis at pCa 4.66. These results enabled us to calculate the cross-bridge distribution in the strongly attached states, and thereby deduce the force/cross-bridge. The results indicate that the force/cross-bridge is ∼15% less in E54K than WT, but remains similar to that of the WT protein in the case of E40K. We conclude that over-inhibition of the actomyosin interaction by E40K and E54K Tm mutants leads to a decreased force-generating ability at systole, which is the main mechanism underlying the early pathogenesis of DCM. 相似文献
7.
Zhenxing Sun Mingxing Xie Feixiang Xiang Yue Song Cheng Yu Yanrong Zhang Sachin Ramdhany Jing Wang 《PloS one》2015,10(9)
Real-time shear-wave elastography (SWE) is a newly developed method which can obtain the stiffness of tissues and organs based on tracking of shear wave propagation through a structure. Several studies have demonstrated its potential in the differentiation between diseased and normal tissue in clinical practices, however the applicability to testicular disease has not been well elucidated. We investigated the feasibility and reproducibility of SWE in the detection of testicular torsion. This prospective study comprised 15 patients with complete testicular torsion. Results obtained from SWE along with conventional gray-scale and color Doppler sonography and post-operative pathology were compared. The results revealed that (i) the size of injured testis was increased and the twisted testis parenchyma was heterogeneous. The blood flow signals in injured testis were barely visible or absent; (ii) The Young’s modulus, including Emean, Emax, Emin and SD values in the border area of torsional testis were higher than those of normal testis (Emean, 78.07±9.01kPa vs 22.0±5.10kPa; Emax,94.07±6.53kPa vs 27.87±5.78kPa; Emin, 60.73±7.84 kPa vs 18.90±4.39kPa; SD, 7.67±0.60 kPa vs 2.30±0.36 kPa, [P<0.05]); The Emax and SD values in the central area of the torsional testis were higher than the corresponding area of the normal testis (Emax, 8.23±0.30 kPa vs 3.97±0.95kPa; SD, 1.5±0.26kPa vs 0.67±0.35kPa,[P<0.05]) and Emin values was lower than those of normal testicles(0.93±0.51kPa vs 1.6±0.36kPa; [P<0.05]); (iii) The Young''s modulus measurement between two physicians showed good agreement. The pathological findings were accordance with SWE measurement. SWE is a non-invasive, convenient and high reproducible method and may serve as an important alternative tool in the diagnosis and monitoring the progression of the acute scrotums, in additional to conventional Doppler sonography. 相似文献
8.
Cristobal Rodero Marina Strocchi Maciej Marciniak Stefano Longobardi John Whitaker Mark D. ONeill Karli Gillette Christoph Augustin Gernot Plank Edward J. Vigmond Pablo Lamata Steven A. Niederer 《PLoS computational biology》2021,17(4)
Cardiac anatomy plays a crucial role in determining cardiac function. However, there is a poor understanding of how specific and localised anatomical changes affect different cardiac functional outputs. In this work, we test the hypothesis that in a statistical shape model (SSM), the modes that are most relevant for describing anatomy are also most important for determining the output of cardiac electromechanics simulations. We made patient-specific four-chamber heart meshes (n = 20) from cardiac CT images in asymptomatic subjects and created a SSM from 19 cases. Nine modes captured 90% of the anatomical variation in the SSM. Functional simulation outputs correlated best with modes 2, 3 and 9 on average (R = 0.49 ± 0.17, 0.37 ± 0.23 and 0.34 ± 0.17 respectively). We performed a global sensitivity analysis to identify the different modes responsible for different simulated electrical and mechanical measures of cardiac function. Modes 2 and 9 were the most important for determining simulated left ventricular mechanics and pressure-derived phenotypes. Mode 2 explained 28.56 ± 16.48% and 25.5 ± 20.85, and mode 9 explained 12.1 ± 8.74% and 13.54 ± 16.91% of the variances of mechanics and pressure-derived phenotypes, respectively. Electrophysiological biomarkers were explained by the interaction of 3 ± 1 modes. In the healthy adult human heart, shape modes that explain large portions of anatomical variance do not explain equivalent levels of electromechanical functional variation. As a result, in cardiac models, representing patient anatomy using a limited number of modes of anatomical variation can cause a loss in accuracy of simulated electromechanical function. 相似文献
9.
Agnieszka Zmyslowska Bogdan Malkowski Wojciech Fendler Maciej Borowiec Karolina Antosik Piotr Gnys Dobromila Baranska Wojciech Mlynarski 《PloS one》2014,9(12)
Wolfram syndrome (WFS) is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography) and MRI (magnetic resonance imaging) in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs) based on images of (18F) fluorodeoxyglucose (FDG) uptake in 7 WFS patients aged 10.1–16.0 years (mean 12.9±2.4) and in 20 healthy children aged 3–17.9 years (mean 12.8±4.1). In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups <13 years old and>13 years old to account for developmental differences. Reduced SUVs in WFS patients as compared to the control group for the bilateral brain regions such as occipital lobe (−1.24±1.20 vs. −0.13±1.05; p = 0.028) and cerebellum (−1.11±0.69 vs. −0.204±1.00; p = 0.036) were observed and the same tendency for cingulate (−1.13±1.05 vs. −0.15±1.12; p = 0.056), temporal lobe (−1.10±0.98 vs. −0.15±1.10; p = 0.057), parietal lobe (−1.06±1.20 vs. −0.08±1.08; p = 0.058), central region (−1.01±1.04 vs. −0.09±1.06; p = 0.060), basal ganglia (−1.05±0.74 vs. −0.20±1.07; p = 0.066) and mesial temporal lobe (−1.06±0.82 vs. −0.26±1.08; p = 0.087) was also noticed. After adjusting for multiple hypothesis testing, the differences in glucose uptake were non-significant. For the first time, regional differences in brain glucose metabolism among patients with WFS were shown using PET-CT imaging. 相似文献
10.
David Vállez Garcia Cindy Casteels Adam J. Schwarz Rudi A. J. O. Dierckx Michel Koole Janine Doorduin 《PloS one》2015,10(3)
High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70±0.32mm for [18F]FDG (n = 25), 0.23±0.10mm for [11C]flumazenil (n = 13), 0.88±0.20 mm for [11C]MeDAS (n = 15), 0.64±0.28mm for [11C]PK11195 (n = 19), 0.34±0.15mm for [11C]raclopride (n = 6), and 0.40±0.13mm for [99mTc]HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p&0.001). Additionally, registration errors were smallest with strain-specific templates (p&0.05), and when images and templates had the same size (p≤0.001). Moreover, highest registration errors were found for the focal lesion group (p&0.005) and the diffuse lesion group (p = n.s.). In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer-specific templates allows accurate registration of functional rat brain data, independent of disease specific uptake patterns and with registration error below spatial resolution of the cameras. The templates and the SAMIT package will be freely available for the research community. 相似文献
11.
12.
The second-order rate constants for the microbial transformation of a series of phenols were correlated with the physicochemical properties of the phenols. The compounds studied were phenol, p-methylphenol, p-chlorophenol, p-bromophenol, p-cyanophenol, p-nitrophenol, p-acetylphenol, and p-methoxyphenol. Phenol-grown cells of Pseudomonas putida U transformed these compounds. Microbial transformation rate constants ranged from (1.5 ± 0.99) × 10−14 liter · organism−1 · h−1 for p-cyanophenol to (7.0 ± 1.3) × 10−12 liter · organism−1 · h−1 for phenol. Linear regression analyses of rate constants and electronic, steric, and hydrophobic parameters showed that van der Waal's radii gave the best coefficient of determination (r2 = 0.956). Products identified by thin-layer chromatography and liquid chromatography indicated that the phenols were microbially oxidized to the corresponding catechols. 相似文献
13.
The purpose of this study is to assess the repeatability of the quantification of pseudo-intracellular sodium concentration (C1) and pseudo-extracellular volume fraction (α) estimated in brain in vivo using sodium magnetic resonance (MRI) at 3 T. Eleven healthy subjects were scanned twice, with two sodium MRI acquisitions (with and without fluid suppression by inversion recovery), and two double inversion recovery (DIR) proton MRI. DIR MRIs were used to create masks of gray and white matter (GM, WM), that were subsequently applied to the C1 and α maps calculated from sodium MRI and a tissue three-compartment model, in order to measure the distributions of these two parameters in GM, WM or full brain (GM+WM) separately. The mean, median, mode, standard deviation (std), skewness and kurtosis of the C1 and α distributions in whole GM, WM and full brain were calculated for each subject, averaged over all data, and used as parameters for the repeatability assessment. The coefficient of variation (CV) was calculated as a measure of reliability for the detection of intra-subject changes in C1 and αfor each parameter, while intraclass correlation (ICC) was used as a measure of repeatability. It was found that the CV of most of the parameters was around 10–20% (except for C1 kurtosis which is about 40%) for C1 and α measurements, and that ICC was moderate to very good (0.4 to 0.9) for C1 parameters and for some of the α parameters (mainly skewness and kurtosis). In conclusion, the proposed method could allow to reliably detect changes of 50% and above of the different measurement parameters of C1 and αin neuropathologies (multiple sclerosis, tumor, stroke, Alzheimer’s disease) compared to healthy subjects, and that skewness and kurtosis of the distributions of C1 and αseem to be the more sensitive parameters to these changes. 相似文献
14.
Magorzata Gadyszyska Justyna Bobrowska Magorzata Lekka Paulina Radwaska Lucyna Piera Jacek Szymaski Jacek Drobnik 《Journal of cellular and molecular medicine》2020,24(23):13853
Cardiac fibroblasts are able to sense the rigidity of their environment. The present study examines whether the stiffness of the substrate in cardiac fibroblast culture can influence the release of interleukin‐6 (IL‐6), interleukin‐11 (IL‐11) and soluble receptor of IL‐6 (sIL‐6R). It also examines the roles of integrin α2β1 activation and intracellular signalling in these processes. Cardiac fibroblasts were cultured on polyacrylamide gels and grafted to collagen, with an elasticity of E = 2.23 ± 0.8 kPa (soft gel) and E = 8.28 ± 1.06 kPa (stiff gel, measured by Atomic Force Microscope). Flow cytometry and ELISA demonstrated that the fibroblasts cultured on the soft gel demonstrated higher expression of the α2 integrin subunit and increased α2β1 integrin count and released higher levels of IL‐6 and sIL‐6R than those on the stiff gel. Substrate elasticity did not modify fibroblast IL‐11 content. The silencing of the α2 integrin subunit decreased the release of IL‐6. Similar effects were induced by TC‐I 15 (an α2β1 integrin inhibitor). The IL‐6 levels in the serum and heart were markedly lower in α2 integrin‐deficient mice B6.Cg‐Itga2tm1.1Tkun/tm1.1Tkun than wild type. Inhibition of Src kinase by AZM 475271 modifies the IL‐6 level. sIL‐6R secretion is not dependent on α2β1 integrin. Conclusion: The elastic properties of the substrate influence the release of IL‐6 by cardiac fibroblasts, and this effect is dependent on α2β1 integrin and kinase Src activation. 相似文献
15.
Paphiopedilum dianthum and P. micranthum are two endangered orchid species, with high ornamental and conservation values. They are sympatric species, but their leaf anatomical traits and flowering period have significant differences. However, it is unclear whether the differences in leaf structure of the two species will affect their adaptabilities to temperature. Here, we investigated the leaf photosynthetic, anatomical, and flowering traits of these two species at three sites with different temperatures (Kunming, 16.7 ± 0.2 °C; Puer, 17.7 ± 0.2 °C; Menglun, 23.3 ± 0.2 °C) in southwest China. Compared with those at Puer and Kunming, the values of light-saturated photosynthetic rate (Pmax), stomatal conductance (gs), leaf thickness (LT), and stomatal density (SD) in both species were lower at Menglun. The values of Pmax, gs, LT, adaxial cuticle thickness (CTad) and SD in P. dianthum were higher than those of P. micranthum at the three sites. Compared with P. dianthum, there were no flowering plants of P. micranthum at Menglun. These results indicated that both species were less resistance to high temperature, and P. dianthum had a stronger adaptability to high-temperature than P. micranthum. Our findings can provide valuable information for the conservation and cultivation of Paphiopedilum species. 相似文献
16.
17.
Nadia A. Longo Carbajosa Gerardo Corradi María A. Lopez Verrilli María J. Guil Marcelo S. Vatta Mariela M. Gironacci 《PloS one》2015,10(2)
Aberrations in the ubiquitin-proteasome system (UPS) are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR) and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86±15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2±8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92±22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7±0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasme activity. Proteasome activity was significantly reduced by 67±4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension. 相似文献
18.
Purpose
To compare the accuracy of magnetic resonance elastography (MRE) with that of aspartate aminotransferase-to-platelet ratio index (APRI) for estimating the stage of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection.Materials and Methods
We retrospectively enrolled 160 patients with chronic hepatitis and 25 healthy living liver donors. Fibrosis stage (METAVIR, F0 to F4) was determined histopathologically for all patients. APRI was recorded at the time of histopathologic examination and liver stiffness values were measured on MRE quantitative stiffness maps. The cutoff values, sensitivity, and specificity of MRE and APRI for each fibrosis stage were determined using receiver operating characteristic (ROC) analysis.Results
MRE had a significantly greater area under the ROC curve than APRI score for discriminating among METAVIR stages F2-F4. Using a cutoff value of 2.80 kPa, MRE had a sensitivity of 94.4% and a specificity of 97.8% for detecting significant fibrosis (≥F2). There were no significant differences in fibrosis stage between patients with HBV and those with HCV infection. For ≥F2, the cutoffs were 2.47 kPa (100% sensitivity), 2.80 kP (maximum sum of sensitivity and specificity), and 3.70 kPa (100% specificity).Conclusions
MRE is a more accurate modality than APRI for detecting significant fibrosis in patients with chronic HBV or HCV infection. Antiviral treatment should be considered in patients with liver stiffness values ≥ 2.8 kPa. 相似文献19.
K. Abigail Andrews Marc Modat Kate E. Macdonald Tom Yeatman M. Jorge Cardoso Kelvin K. Leung Josephine Barnes Victor L. Villemagne Christopher C. Rowe Nick C. Fox Sebastien Ourselin Jonathan M. Schott the Australian Imaging Biomarkers Lifestyle Flagship Study of Ageing 《PloS one》2013,8(3)
There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have shown that ∼1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3) from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB) PET scan and two 3T MRI scans ∼18-months apart. We calculated PET standard uptake value ratios (SUVR), and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014). Twenty-two (1/3) were PiB-positive (SUVR>1.40), the remaining 44 PiB-negative (SUVR≤1.31). Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02), independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr) and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr) change. Based on the observed effect size, recruiting 384 (95%CI 195–1080) amyloid-positive subjects/arm will provide 80% power to detect 25% absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis. 相似文献
20.
John Paul V. Anders Joshua L. Keller Tyler J. Neltner Terry J. Housh Richard J. Schmidt Glen O. Johnson 《Journal of musculoskeletal & neuronal interactions》2021,21(1):4
Objectives:The purpose of the present study was to compare the fatigue-induced changes in performance fatigability, bilateral deficit, and patterns of responses for the electromyographic (EMG) and mechanomyographic (MMG) amplitude (AMP) and mean power frequency (MPF), during unilateral and bilateral maximal, fatiguing leg extensions.Methods:Nine men (Mean±SD; age =21.9±2.4 yrs; height =181.8±11.9 cm; body mass =85.8±6.2 kg) volunteered to perform 50 consecutive maximal, bilateral (BL), unilateral dominant (DL), and unilateral non-dominant (NL) isokinetic leg extensions at 180°·s-1, on 3 separate days. Electromyographic and MMG signals from both vastus lateralis (VL) muscles were recorded. Repeated measures ANOVAs were utilized to examine mean differences in normalized force, EMG AMP, EMG MPF, MMG AMP, MMG MPF and the bilateral deficit.Results:The results demonstrated a Condition × Repetition interaction for normalized force (p=0.004, η2p=0.222) and EMG MPF (p=0.034, η2p=0.214) and main effects for Repetition for EMG AMP (p=0.019, η2p=0.231), MMG AMP (p<0.001, η2p=0.8550), MMG MPF (p=0.009, η2p=0.252), and the bilateral deficit (p<0.001, η2p=0.366).Conclusions:The findings demonstrated less performance fatigability during the BL than the unilateral tasks, likely due to a reduced relative intensity via interhemispheric inhibition that attenuated the development of excitation-contraction coupling failure during the BL task. 相似文献