Sample records for t1 t2 t3

  1. Comparison of post-contrast 3D-T1-MPRAGE, 3D-T1-SPACE and 3D-T2-FLAIR MR images in evaluation of meningeal abnormalities at 3-T MRI.

    PubMed

    Jeevanandham, Balaji; Kalyanpur, Tejas; Gupta, Prashant; Cherian, Mathew

    2017-06-01

    This study was to assess the usefulness of newer three-dimensional (3D)-T 1 sampling perfection with application optimized contrast using different flip-angle evolutions (SPACE) and 3D-T 2 fluid-attenuated inversion recovery (FLAIR) sequences in evaluation of meningeal abnormalities. 78 patients who presented with high suspicion of meningeal abnormalities were evaluated using post-contrast 3D-T 2 -FLAIR, 3D-T 1 magnetization-prepared rapid gradient-echo (MPRAGE) and 3D-T 1 -SPACE sequences. The images were evaluated independently by two radiologists for cortical gyral, sulcal space, basal cisterns and dural enhancement. The diagnoses were confirmed by further investigations including histopathology. Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images yielded significantly more information than MPRAGE images (p < 0.05 for both SPACE and FLAIR images) in detection of meningeal abnormalities. SPACE images best demonstrated abnormalities in dural and sulcal spaces, whereas FLAIR was useful for basal cisterns enhancement. Both SPACE and FLAIR performed equally well in detection of gyral enhancement. In all 10 patients, where both SPACE and T 2 -FLAIR images failed to demonstrate any abnormality, further analysis was also negative. The 3D-T 1 -SPACE sequence best demonstrated abnormalities in dural and sulcal spaces, whereas FLAIR was useful for abnormalities in basal cisterns. Both SPACE and FLAIR performed holds good for detection of gyral enhancement. Post-contrast SPACE and FLAIR sequences are superior to the MPRAGE sequence for evaluation of meningeal abnormalities and when used in combination have the maximum sensitivity for leptomeningeal abnormalities. The negative-predictive value is nearly 100%, where no leptomeningeal abnormality was detected on these sequences. Advances in knowledge: Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images are more useful than 3D-T 1 -MPRAGE images in evaluation of meningeal abnormalities.

  2. Obtaining T1-T2 distribution functions from 1-dimensional T1 and T2 measurements: The pseudo 2-D relaxation model

    NASA Astrophysics Data System (ADS)

    Williamson, Nathan H.; Röding, Magnus; Galvosas, Petrik; Miklavcic, Stanley J.; Nydén, Magnus

    2016-08-01

    We present the pseudo 2-D relaxation model (P2DRM), a method to estimate multidimensional probability distributions of material parameters from independent 1-D measurements. We illustrate its use on 1-D T1 and T2 relaxation measurements of saturated rock and evaluate it on both simulated and experimental T1-T2 correlation measurement data sets. Results were in excellent agreement with the actual, known 2-D distribution in the case of the simulated data set. In both the simulated and experimental case, the functional relationships between T1 and T2 were in good agreement with the T1-T2 correlation maps from the 2-D inverse Laplace transform of the full 2-D data sets. When a 1-D CPMG experiment is combined with a rapid T1 measurement, the P2DRM provides a double-shot method for obtaining a T1-T2 relationship, with significantly decreased experimental time in comparison to the full T1-T2 correlation measurement.

  3. Core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Li, Fenfen; Zhi, Debo; Luo, Yufeng; Zhang, Jiqian; Nan, Xiang; Zhang, Yunjiao; Zhou, Wei; Qiu, Bensheng; Wen, Longping; Liang, Gaolin

    2016-06-01

    T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes

  4. Preoperative detection of malignant liver tumors: Comparison of 3D-T2-weighted sequences with T2-weighted turbo spin-echo and single shot T2 at 1.5 T.

    PubMed

    Barat, Maxime; Soyer, Philippe; Dautry, Raphael; Pocard, Marc; Lo-Dico, Rea; Najah, Haythem; Eveno, Clarisse; Cassinotto, Christophe; Dohan, Anthony

    2018-03-01

    To assess the performances of three-dimensional (3D)-T2-weighted sequences compared to standard T2-weighted turbo spin echo (T2-TSE), T2-half-Fourier acquisition single-shot turbo spin-echo (T2-HASTE), diffusion weighted imaging (DWI) and 3D-T1-weighted VIBE sequences in the preoperative detection of malignant liver tumors. From 2012 to 2015, all patients of our institution undergoing magnetic resonance imaging (MRI) examination for suspected malignant liver tumors were prospectively included. Patients had contrast-enhanced 3D-T1-weighted, DWI, 3D-T2-SPACE, T2-HASTE and T2-TSE sequences. Imaging findings were compared with those obtained at follow-up, surgery and histopathological analysis. Sensitivities for the detection of malignant liver tumors were compared for each sequence using McNemar test. A subgroup analysis was conducted for HCCs. Image artifacts were analyzed and compared using Wilcoxon paired signed rank-test. Thirty-three patients were included: 13 patients had 40 hepatocellular carcinomas (HCC) and 20 had 54 liver metastases. 3D-T2-weighted sequences had a higher sensitivity than T2-weighted TSE sequences for the detection of malignant liver tumors (79.8% versus 68.1%; P < 0.001). The difference did not reach significance for HCC. T1-weighted VIBE and DWI had a higher sensitivity than T2-weighted sequences. 3D-T2-weighted-SPACE sequences showed significantly less artifacts than T2-weitghted TSE. 3D-T2-weighted sequences show very promising performances for the detection of liver malignant tumors compared to T2-weighted TSE sequences. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    PubMed

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  6. Simultaneous acquisition for T2 -T2 Exchange and T1 -T2 correlation NMR experiments

    NASA Astrophysics Data System (ADS)

    Montrazi, Elton T.; Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Barsi-Andreeta, Mariane; Bonagamba, Tito J.

    2018-04-01

    The NMR measurements of longitudinal and transverse relaxation times and its multidimensional correlations provide useful information about molecular dynamics. However, these experiments are very time-consuming, and many researchers proposed faster experiments to reduce this issue. This paper presents a new way to simultaneously perform T2 -T2 Exchange and T1 -T2 correlation experiments by taking the advantage of the storage time and the two steps phase cycling used for running the relaxation exchange experiment. The data corresponding to each step is either summed or subtracted to produce the T2 -T2 and T1 -T2 data, enhancing the information obtained while maintaining the experiment duration. Comparing the results from this technique with traditional NMR experiments it was possible to validate the method.

  7. Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3 T

    PubMed Central

    Li, Yan; Srinivasan, Radhika; Ratiney, Helene; Lu, Ying; Chang, Susan M.; Nelson, Sarah J.

    2011-01-01

    Purpose To measure T1 and T2 relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. Materials and Methods Twenty-three patients with gliomas and ten volunteers were studied with single voxel 2D J-resolved PRESS using a 3T MR scanner. Voxels were chosen in normal appearing white matter and in regions of tumor. The T1 and T2 of choline containing compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) were estimated. Results Metabolite T1 relaxation values in gliomas were not significantly different from values in normal white matter. The T2 of Cho and Cr were statistically significantly longer for Grade 4 gliomas than for normal white matter but the T2 of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P<0.001). Conclusion The differential increase in T2 for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MRSI data, where limited time is available and only one echo time can be used. PMID:18666155

  8. Measurement of T1 of the Ultrashort T2* Components in White Matter of the Brain at 3T

    PubMed Central

    Du, Jiang; Sheth, Vipul; He, Qun; Carl, Michael; Chen, Jun; Corey-Bloom, Jody; Bydder, Graeme M.

    2014-01-01

    Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32±0.09 ms, and a short mean T1 of 226±46 ms were demonstrated for the healthy volunteers at 3T. PMID:25093859

  9. Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls.

    PubMed

    Chen, Xiaopeng; Walter, Kyla M; Miller, Galen W; Lein, Pamela J; Puschner, Birgit

    2018-06-01

    Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-l-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2) and 3,3'-diiodo-l-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode. Solid-phase extraction with SampliQ cartridges and derivatization with 3 m hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an Acquity UPLC BEH C 18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5 to 0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 h of exposure to polychlorinated biphenyls (PCBs), including PCB 28, PCB 66 and PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs. Copyright © 2018 John Wiley & Sons, Ltd.

  10. Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

    PubMed

    Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

    2018-05-01

    The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

  11. Glycine transporters GlyT1 and GlyT2 are differentially modulated by glycogen synthase kinase 3β.

    PubMed

    Jiménez, Esperanza; Núñez, Enrique; Ibáñez, Ignacio; Zafra, Francisco; Aragón, Carmen; Giménez, Cecilio

    2015-02-01

    Inhibitory glycinergic neurotransmission is terminated by the specific glycine transporters GlyT1 and GlyT2 which actively reuptake glycine from the synaptic cleft. GlyT1 is associated with both glycinergic and glutamatergic pathways, and is the main regulator of the glycine levels in the synapses. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is vital to preserve the quantal glycine content in synaptic vesicles. Therefore, to control glycinergic neurotransmission efficiently, GlyT1 and GlyT2 activity must be regulated by diverse neuronal and glial signaling pathways. In this work, we have investigated the possible functional modulation of GlyT1 and GlyT2 by glycogen synthase kinase 3 (GSK3β). This kinase is involved in mood stabilization, neurodegeneration and plasticity at excitatory and inhibitory synapses. The co-expression of GSK3β with GlyT1 or GlyT2 in COS-7 cells and Xenopus laevis oocytes, leads to inhibition and stimulation of GlyT1 and GlyT2 activities, respectively, with a decrease of GlyT1, and an increase in GlyT2 levels at the plasma membrane. The specificity of these changes is supported by the antagonism exerted by a catalytically inactive form of the kinase and through inhibitors of GSK3β such as lithium chloride and TDZD-8. GSK3β also increases the incorporation of 32Pi into GlyT1 and decreases that of GlyT2. The pharmacological inhibition of the endogenous GSK3β in neuron cultures of brainstem and spinal cord leads to an opposite modulation of GlyT1 and GlyT2.Our results suggest that GSK3β is important for stabilizing and/or controlling the expression of functional GlyTs on the neural cell surface. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

    NASA Astrophysics Data System (ADS)

    Hu, Fengqin; Zhao, Yong Sheng

    2012-09-01

    Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

  13. A systematic evaluation of three different cardiac T2-mapping sequences at 1.5 and 3T in healthy volunteers.

    PubMed

    Baeßler, Bettina; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Maintz, David; Bunck, Alexander C

    2015-11-01

    Previous studies showed that myocardial T2 relaxation times measured by cardiac T2-mapping vary significantly depending on sequence and field strength. Therefore, a systematic comparison of different T2-mapping sequences and the establishment of dedicated T2 reference values is mandatory for diagnostic decision-making. Phantom experiments using gel probes with a range of different T1 and T2 times were performed on a clinical 1.5T and 3T scanner. In addition, 30 healthy volunteers were examined at 1.5 and 3T in immediate succession. In each examination, three different T2-mapping sequences were performed at three short-axis slices: Multi Echo Spin Echo (MESE), T2-prepared balanced SSFP (T2prep), and Gradient Spin Echo with and without fat saturation (GraSEFS/GraSE). Segmented T2-Maps were generated according to the AHA 16-segment model and statistical analysis was performed. Significant intra-individual differences between mean T2 times were observed for all sequences. In general, T2prep resulted in lowest and GraSE in highest T2 times. A significant variation with field strength was observed for mean T2 in phantom as well as in vivo, with higher T2 values at 1.5T compared to 3T, regardless of the sequence used. Segmental T2 values for each sequence at 1.5 and 3T are presented. Despite a careful selection of sequence parameters and volunteers, significant variations of the measured T2 values were observed between field strengths, MR sequences and myocardial segments. Therefore, we present segmental T2 values for each sequence at 1.5 and 3T with the inherent potential to serve as reference values for future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy

    PubMed Central

    Wood, John C.; Otto-Duessel, Maya; Aguilar, Michelle; Nick, Hanspeter; Nelson, Marvin D.; Coates, Thomas D.; Pollack, Harvey; Moats, Rex

    2010-01-01

    Background Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. Methods and Results Twelve gerbils underwent iron dextran loading (200 mg · kg−1 · wk−1) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis. Conclusions MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans. PMID:16027257

  15. Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

    PubMed

    Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

    2018-03-01

    Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This

  16. Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

    PubMed

    Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

    2016-10-11

    The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

  17. Ultra-low field T1 vs. T1rho at 3T and 7T: study of rotationally immobilized protein gels and animal brain tissues

    NASA Astrophysics Data System (ADS)

    Dong, Hui; Inglis, Ben; Barr, Ian; Clarke, John

    2015-03-01

    Clinical magnetic resonance imaging (MRI) machines operating in static fields of typically 1.5 T or 3 T can capture information on slow molecular dynamics utilizing the so-called T1rho technique. This technique, in which a radiofrequency (RF) spin-lock field is applied with microtesla amplitude, has been used, for example, to determine the onset time of stroke in studies on rats. The long RF pulse, however, may exceed the specific absorption rate (SAR) limit, putting subjects at risk. Ultra-low-field (ULF) MRI, based on Superconducting Quantum Interference Devices (SQUIDs), directly detects proton signals at a static magnetic field of typically 50-250 μT. Using our ULF MRI system with adjustable static field of typically 55 to 240 μT, we systematically measured the T1 and T2 dispersion profiles of rotationally immobilized protein gels (bovine serum albumin), ex vivo pig brains, and ex vivo rat brains with induced stroke. Comparing the ULF results with T1rho dispersion obtained at 3 T and 7 T, we find that the degree of protein immobilization determines the frequency-dependence of both T1 and T1rho. Furthermore, T1rho and ULF T1 show similar results for stroke, suggesting that ULF MRI may be used to image traumatic brain injury with negligible SAR. This research was supported by the Henry H. Wheeler, Jr. Brain Imaging Center and the Donaldson Trust.

  18. Local T1-T2 distribution measurements in porous media

    NASA Astrophysics Data System (ADS)

    Vashaee, S.; Li, M.; Newling, B.; MacMillan, B.; Marica, F.; Kwak, H. T.; Gao, J.; Al-harbi, A. M.; Balcom, B. J.

    2018-02-01

    A novel slice-selective T1-T2 measurement is proposed to measure spatially resolved T1-T2 distributions. An adiabatic inversion pulse is employed for slice-selection. The slice-selective pulse is able to select a quasi-rectangular slice, on the order of 1 mm, at an arbitrary position within the sample. The method does not employ conventional selective excitation in which selective excitation is often accomplished by rotation of the longitudinal magnetization in the slice of interest into the transverse plane, but rather a subtraction based on CPMG data acquired with and without adiabatic inversion slice selection. T1 weighting is introduced during recovery from the inversion associated with slice selection. The local T1-T2 distributions measured are of similar quality to bulk T1-T2 measurements. The new method can be employed to characterize oil-water mixtures and other fluids in porous media. The method is beneficial when a coarse spatial distribution of the components is of interest.

  19. Evaluation of multimodal segmentation based on 3D T1-, T2- and FLAIR-weighted images - the difficulty of choosing.

    PubMed

    Lindig, Tobias; Kotikalapudi, Raviteja; Schweikardt, Daniel; Martin, Pascal; Bender, Friedemann; Klose, Uwe; Ernemann, Ulrike; Focke, Niels K; Bender, Benjamin

    2018-04-15

    Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35.8 years, 19-66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28.1 years,19-40 years, 3 females), and 5 patients with left hippocampal sclerosis (LHS) (mean age 49.0 years, 25-67 years, 3 females) from a 3T scanner were evaluated. Segmentation based on T1-only, T1+T2, T1+FLAIR, T2+FLAIR, and T1+T2+FLAIR were compared in the healthy subjects. Clinical VBM results based on the different segmentation approaches for MCD and for LHS were compared. T1-only segmentation overestimated total intracranial volume by about 80ml compared to the other segmentation methods. This was due to misclassification of dura mater and vessels as GM and CSF. Significant differences were found for several anatomical regions: the occipital lobe, the basal ganglia/thalamus, the pre- and postcentral gyrus, the cerebellum, and the brainstem. None of the segmentation methods yielded completely satisfying results for the basal ganglia/thalamus and the brainstem. The best correlation with age could be found for the multimodal T1+T2+FLAIR segmentation. Highest T-scores for identification of LHS were found for T1+T2 segmentation, while highest T-scores for MCD were dependent on lesion and anatomical location. Multimodal segmentation is superior to T1-only segmentation and reduces the misclassification of dura mater and vessels as GM and CSF. Depending on the anatomical region and the pathology of interest (atrophy, lesion detection, etc.), different combinations of T1, T2 and FLAIR yield optimal results. Copyright © 2017 Elsevier

  20. Cluster analysis of quantitative MRI T2 and T1ρ relaxation times of cartilage identifies differences between healthy and ACL-injured individuals at 3T.

    PubMed

    Monu, U D; Jordan, C D; Samuelson, B L; Hargreaves, B A; Gold, G E; McWalter, E J

    2017-04-01

    To identify focal lesions of elevated MRI T 2 and T 1ρ relaxation times in articular cartilage of an ACL-injured group using a novel cluster analysis technique. Eighteen ACL-injured patients underwent 3T MRI T 2 and T 1ρ relaxometry at baseline, 6 months and 1 year and six healthy volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or below T 2 and T 1ρ intensity and area thresholds were identified on a projection map of the 3D femoral cartilage surface. The total area of femoral cartilage plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA-) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured group were determined using the Wilcoxon signed rank test. %CA+ was greater in the ACL-injured patients than the healthy volunteers at 6 months and 1 year with average %CA+ of 5.2 ± 4.0% (p = 0.0054) and 6.6 ± 3.7% (p = 0.0041) for T 2 and 6.2 ± 7.1% (p = 0.063) and 8.2 ± 6.9% (p = 0.042) for T 1ρ , respectively. %CA- at 6 months and 1 year was 3.0 ± 1.8% (p > 0.1) and 5.9 ± 5.0% (p > 0.1) for T 2 and 4.4 ± 4.9% (p > 0.1) and 4.5 ± 4.6% (p > 0.1) for T 1ρ , respectively. With the proposed cluster analysis technique, we have quantified cartilage lesion coverage and demonstrated that the ACL-injured group had greater areas of elevated T 2 and T 1ρ relaxation times as compared to healthy volunteers. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. Synthesis and characterization of two layered aluminophosphates, ( T) 2HAl 2P 3O 12 ( T=2-BuNH 3+) and ( T)H 2Al 2P 3O 12 ( T=pyH +)

    NASA Astrophysics Data System (ADS)

    Chippindale, Ann M.; Powell, Anthony V.; Bull, Lucy M.; Jones, Richard H.; Cheetham, Anthony K.; Thomas, John M.; Xu, Ruren

    1992-01-01

    Two new aluminophosphates, ( T) 2HAl 2P 3O 12 ( T=2-BuNH 3+) ( I) and ( T)H 2Al 2P 3O 12 ( T=pyH +) ( II) with the same framework stoichiometry but different layer structures have been prepared under nonaqueous conditions and the structures determined by single-crystal X-ray diffraction. Compound ( I) crystallizes in the monoclinic space group P2 1/ c ( Z=4), with lattice parameters a=9.261(1) b=8.365(6), c=27.119(4) Å, β=91.50(1)δ, and V=2100.1 Å 3 ( R=0.072 and R w=0.090). The structure consists of Al-and P-centered tetrahedra linked to form layers. Protonated 2-butylamine molecules are located in the interlayer spaces and hydrogen bonded to the layers through NH 3+ groups. Weak hydrophobic van der Waals' interactions between alkyl groups of the 2-BuNH 3+ cations hold the layers together. Compound ( II) crystallizes in the triclinic space group P-1 ( Z=2), with a=8.574(2), b=8.631(3), c=10.371(2) Å, α=81.84(3), β=87.53(2), γ=69.07(2)δ, and V=709.49Å 3 ( R=0.039 and R w=0.052). The structure contains tetrahedrally coordinated P atoms and both tetrahedral and trigonal pyramidal Al atoms linked to form layers which are held together through hydrogen bonding, creating cavities in which pyH + cations reside.

  2. Clinical radiobiology of stage T2-T3 bladder cancer.

    PubMed

    Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

    2004-09-01

    To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which

  3. 3D T2-weighted and Gd-EOB-DTPA-enhanced 3D T1-weighted MR cholangiography for evaluation of biliary anatomy in living liver donors.

    PubMed

    Cai, Larry; Yeh, Benjamin M; Westphalen, Antonio C; Roberts, John; Wang, Zhen J

    2017-03-01

    To investigate whether the addition of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced 3D T1-weighted MR cholangiography (T1w-MRC) to 3D T2-weighted MRC (T2w-MRC) improves the confidence and diagnostic accuracy of biliary anatomy in living liver donors. Two abdominal radiologists retrospectively and independently reviewed pre-operative MR studies in 58 consecutive living liver donors. The second-order bile duct visualization on T1w- and T2w-MRC images was rated on a 4-point scale. The readers also independently recorded the biliary anatomy and their diagnostic confidence using (1) combined T1w- and T2w-MRC, and (2) T2w-MRC. In the 23 right lobe donors, the biliary anatomy at imaging and the imaging-predicted number of duct orifices at surgery were compared to intra-operative findings. T1w-MRC had a higher proportion of excellent visualization than T2w-MRC, 66% vs. 45% for reader 1 and 60% vs. 31% for reader 2. The median confidence score for biliary anatomy diagnosis was significantly higher with combined T1w- and T2w-MRC than T2w-MRC alone for both readers (Reader 1: 3 vs. 2, p < 0.001; Reader 2: 3 vs. 1, p < 0.001). Compared to intra-operative findings, the accuracy of imaging-predicted number of duct orifices using combined T1w-and T2w-MRC was significantly higher than that using T2w-MRC alone (p = 0.034 for reader 1, p = 0.0082 for reader 2). The addition of Gd-EOB-DTPA-enhanced 3D T1w-MRC to 3D T2w-MRC improves second-order bile duct visualization and increases the confidence in biliary anatomy diagnosis and the accuracy in the imaging-predicted number of duct orifices acquired during right lobe harvesting.

  4. Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

    PubMed

    Smith, Kimberly R; Spector, Alan C

    2017-10-01

    Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1 ) detectable when both receptor subunits are absent and 2 ) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose. Copyright © 2017 the American Physiological Society.

  5. MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

    PubMed

    Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

    2017-04-01

    To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  6. Definitive Radiotherapy for T1-T2 Squamous Cell Carcinoma of Pyriform Sinus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rabbani, Anna; Amdur, Robert J.; Mancuso, Anthony A.

    2008-10-01

    Purpose: To report the long-term results after definitive radiotherapy (RT) for T1-T2 pyriform sinus squamous cell carcinoma. Patients and Methods: The data from 123 patients with T1-T2 pyriform sinus squamous cell carcinoma treated with RT with or without neck dissection between November 1964 and June 2003 were analyzed. The median follow-up for all patients was 3.2 years, and the median follow-up for living patients was 10.7 years. Results: The 5-year local control, locoregional control, freedom from distant metastasis, cause-specific survival, and overall survival rate was 85%, 70%, 75%, 61%, and 35%, respectively. The ultimate local control rate, including successful salvagemore » of RT failure, for T1 and T2 cancer patients was 96% and 94%, respectively. The overall local control rate with a functional larynx was 83%. Pretreatment computed tomography tumor volume data were available for 55 patients. The median computed tomography tumor volume was 4.2 cm{sup 3} (range, 0-22.4). Local control was worse for patients with a tumor volume >6.5 cm{sup 3} compared with those with a smaller tumor volume. Of the 123 patients, 16% developed moderate to severe acute (2%), late (9%), or postoperative (5%) complications. Conclusions: Local control with larynx preservation after definitive RT for T1-T2 pyriform sinus squamous cell carcinoma likely results in local control and survival similar to that after total laryngectomy or larynx-conserving surgery. Two-thirds of our living patients retained a functional larynx.« less

  7. Correlation study between facet joint cartilage and intervertebral discs in early lumbar vertebral degeneration using T2, T2* and T1ρ mapping

    PubMed Central

    Zhang, Yi; Hu, Jianzhong; Duan, Chunyue; Hu, Ping; Lu, Hongbin; Peng, Xianjing

    2017-01-01

    Recent advancements in magnetic resonance imaging have allowed for the early detection of biochemical changes in intervertebral discs and articular cartilage. Here, we assessed the feasibility of axial T2, T2* and T1ρ mapping of the lumbar facet joints (LFJs) to determine correlations between cartilage and intervertebral discs (IVDs) in early lumbar vertebral degeneration. We recruited 22 volunteers and examined 202 LFJs and 101 IVDs with morphological (sagittal and axial FSE T2-weighted imaging) and axial biochemical (T2, T2* and T1ρ mapping) sequences using a 3.0T MRI scanner. IVDs were graded using the Pfirrmann system. Mapping values of LFJs were recorded according to the degeneration grades of IVDs at the same level. The feasibility of T2, T2* and T1ρ in IVDs and LFJs were analyzed by comparing these mapping values across subjects with different rates of degeneration using Kruskal-Wallis tests. A Pearson’s correlation analysis was used to compare T2, T2* and T1ρ values of discs and LFJs. We found excellent reproducibility in the T2, T2* and T1ρ values for the nucleus pulposus (NP), anterior and posterior annulus fibrosus (PAF), and LFJ cartilage (intraclass correlation coefficients 0.806–0.955). T2, T2* and T1ρ mapping (all P<0.01) had good Pfirrmann grade performances in the NP with IVD degeneration. LFJ T2* values were significantly different between grades I and IV (PL = 0.032, PR = 0.026), as were T1ρ values between grades II and III (PL = 0.002, PR = 0.006) and grades III and IV (PL = 0.006, PR = 0.001). Correlations were moderately negative for T1ρ values between LFJ cartilage and NP (rL = −0.574, rR = −0.551), and between LFJ cartilage and PAF (rL = −0.551, rR = −0.499). T1ρ values of LFJ cartilage was weakly correlated with T2 (r = 0.007) and T2* (r = −0.158) values. Overall, we show that axial T1ρ effectively assesses early LFJ cartilage degeneration. Using T1ρ analysis, we propose a link between LFJ degeneration and IVD NP or

  8. The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential.

    PubMed

    Sprous, Dennis; Palmer, Kyle R

    2010-01-01

    Taste signaling is a critical determinant of ingestive behaviors and thereby linked to obesity and related metabolic dysfunctions. Recent evidence of taste signaling pathways in the gut suggests the link to be more direct, raising the possibility that taste receptor systems could be regarded as therapeutic targets. T1R2/T1R3, the G protein coupled receptor that mediates sweet taste, and the TRPM5 ion channel have been the focus of discovery programs seeking novel compounds that could be useful in modifying taste. We review in this chapter the hypothesis of gastrointestinal taste signaling and discuss the potential for T1R2/T1R3 and TRPM5 as targets of therapeutic intervention in obesity and diabetes. Critical to the development of a drug discovery program is the creation of libraries that enhance the likelihood of identifying novel compounds that modulate the target of interest. We advocate a computer-based chemoinformatic approach for assembling natural and synthetic compound libraries as well as for supporting optimization of structure activity relationships. Strategies for discovering modulators of T1R2/T1R3 and TRPM5 using methods of chemoinformatics are presented herein. Copyright 2010 Elsevier Inc. All rights reserved.

  9. T2-Weighted Liver MRI Using the MultiVane Technique at 3T: Comparison with Conventional T2-Weighted MRI

    PubMed Central

    Kang, Kyung A; Kim, EunJu; Jeong, Woo Kyoung; Choi, Dongil; Lee, Won Jae; Jung, Sin-Ho; Baek, Sun-Young

    2015-01-01

    Objective To assess the value of applying MultiVane to liver T2-weighted imaging (T2WI) compared with conventional T2WIs with emphasis on detection of focal liver lesions. Materials and Methods Seventy-eight patients (43 men and 35 women) with 86 hepatic lesions and 20 pancreatico-biliary diseases underwent MRI including T2WIs acquired using breath-hold (BH), respiratory-triggered (RT), and MultiVane technique at 3T. Two reviewers evaluated each T2WI with respect to artefacts, organ sharpness, and conspicuity of intrahepatic vessels, hilar duct, and main lesion using five-point scales, and made pairwise comparisons between T2WI sequences for these categories. Diagnostic accuracy (Az) and sensitivity for hepatic lesion detection were evaluated using alternative free-response receiver operating characteristic analysis. Results MultiVane T2WI was significantly better than BH-T2WI or RT-T2WI for organ sharpness and conspicuity of intrahepatic vessels and main lesion in both separate reviews and pairwise comparisons (p < 0.001). With regard to motion artefacts, MultiVane T2WI or BH-T2WI was better than RT-T2WI (p < 0.001). Conspicuity of hilar duct was better with BH-T2WI than with MultiVane T2WI (p = 0.030) or RT-T2WI (p < 0.001). For detection of 86 hepatic lesions, sensitivity (mean, 97.7%) of MultiVane T2WI was significantly higher than that of BH-T2WI (mean, 89.5%) (p = 0.008) or RT-T2WI (mean, 84.9%) (p = 0.001). Conclusion Applying the MultiVane technique to T2WI of the liver is a promising approach to improving image quality that results in increased detection of focal liver lesions compared with conventional T2WI. PMID:26357498

  10. Electronic properties of in-plane phase engineered 1T'/2H/1T' MoS2

    NASA Astrophysics Data System (ADS)

    Thakur, Rajesh; Sharma, Munish; Ahluwalia, P. K.; Sharma, Raman

    2018-04-01

    We present the first principles studies of semi-infinite phase engineered MoS2 along zigzag direction. The semiconducting (2H) and semi-metallic (1T') phases are known to be stable in thin-film MoS2. We described the electronic and structural properties of the infinite array of 1T'/2H/1T'. It has been found that 1T'phase induced semi-metallic character in 2H phase beyond interface but, only Mo atoms in 2H phase domain contribute to the semi-metallic nature and S atoms towards semiconducting state. 1T'/2H/1T' system can act as a typical n-p-n structure. Also high holes concentration at the interface of Mo layer provides further positive potential barriers.

  11. Diagnostic value of T1 and T2 * relaxation times and off-resonance saturation effects in the evaluation of Achilles tendinopathy by MRI at 3T.

    PubMed

    Grosse, Ulrich; Syha, Roland; Hein, Tobias; Gatidis, Sergios; Grözinger, Gerd; Schabel, Christoph; Martirosian, Petros; Schick, Fritz; Springer, Fabian

    2015-04-01

    To evaluate and compare the diagnostic value of T1 , T2 * relaxation times and off-resonance saturation ratios (OSR) in healthy controls and patients with different clinical and morphological stages of Achilles tendinopathy. Forty-two healthy Achilles tendons and 34 tendons of 17 patients with symptomatic and asymptomatic tendinopathy were investigated clinically with conventional magnetic resonance imaging (MRI) sequences on a 3T whole-body MR scanner and a dynamic ultrasound examination. In addition, T1 and T2 * relaxation times were assessed using an ultrashort echo time (UTE) imaging sequence with flip angle and echo time variation. For the calculation of OSR values a Gaussian off-resonance saturation pulse (frequency offset: 750-5000 Hz) was used. The diagnostic value of the derived MR values was assessed and compared using receiver operating characteristic (ROC) curves. ROC curves demonstrate the highest overall test performance for OSR values at 2000 Hz off-resonance in differentiating slightly (OSR-2000 [AUC: 0.930] > T2 * [AUC: 0.884] > T1 [AUC: 0.737]) and more severe pathologically altered tendon areas (OSR-2000 [AUC: 0.964] > T2 * [AUC: 0.917] > T1 [AUC: 0.819]) from healthy ones. OSR values at a frequency offset of 2000 Hz demonstrated a better sensitivity and specificity for detecting mild and severe stages of tendinopathy compared to T2 * and particularly when compared to T1 relaxation times. © 2014 Wiley Periodicals, Inc.

  12. Modeling T1 and T2 relaxation in bovine white matter

    NASA Astrophysics Data System (ADS)

    Barta, R.; Kalantari, S.; Laule, C.; Vavasour, I. M.; MacKay, A. L.; Michal, C. A.

    2015-10-01

    The fundamental basis of T1 and T2 contrast in brain MRI is not well understood; recent literature contains conflicting views on the nature of relaxation in white matter (WM). We investigated the effects of inversion pulse bandwidth on measurements of T1 and T2 in WM. Hybrid inversion-recovery/Carr-Purcell-Meiboom-Gill experiments with broad or narrow bandwidth inversion pulses were applied to bovine WM in vitro. Data were analysed with the commonly used 1D-non-negative least squares (NNLS) algorithm, a 2D-NNLS algorithm, and a four-pool model which was based upon microscopically distinguishable WM compartments (myelin non-aqueous protons, myelin water, non-myelin non-aqueous protons and intra/extracellular water) and incorporated magnetization exchange between adjacent compartments. 1D-NNLS showed that different T2 components had different T1 behaviours and yielded dissimilar results for the two inversion conditions. 2D-NNLS revealed significantly more complicated T1/T2 distributions for narrow bandwidth than for broad bandwidth inversion pulses. The four-pool model fits allow physical interpretation of the parameters, fit better than the NNLS techniques, and fits results from both inversion conditions using the same parameters. The results demonstrate that exchange cannot be neglected when analysing experimental inversion recovery data from WM, in part because it can introduce exponential components having negative amplitude coefficients that cannot be correctly modeled with nonnegative fitting techniques. While assignment of an individual T1 to one particular pool is not possible, the results suggest that under carefully controlled experimental conditions the amplitude of an apparent short T1 component might be used to quantify myelin water.

  13. New superhindered polydentate polyphosphine ligands P(CH2CH2P(t)Bu2)3, PhP(CH2CH2P(t)Bu2)2, P(CH2CH2CH2P(t)Bu2)3, and their ruthenium(II) chloride complexes.

    PubMed

    Gilbert-Wilson, Ryan; Field, Leslie D; Bhadbhade, Mohan M

    2012-03-05

    The synthesis and characterization of the extremely hindered phosphine ligands, P(CH(2)CH(2)P(t)Bu(2))(3) (P(2)P(3)(tBu), 1), PhP(CH(2)CH(2)P(t)Bu(2))(2) (PhP(2)P(2)(tBu), 2), and P(CH(2)CH(2)CH(2)P(t)Bu(2))(3) (P(3)P(3)(tBu), 3) are reported, along with the synthesis and characterization of ruthenium chloro complexes RuCl(2)(P(2)P(3)(tBu)) (4), RuCl(2)(PhP(2)P(2)(tBu)) (5), and RuCl(2)(P(3)P(3)(tBu)) (6). The bulky P(2)P(3)(tBu) (1) and P(3)P(3)(tBu) (3) ligands are the most sterically encumbered PP(3)-type ligands so far synthesized, and in all cases, only three phosphorus donors are able to bind to the metal center. Complexes RuCl(2)(PhP(2)P(2)(tBu)) (5) and RuCl(2)(P(3)P(3)(tBu)) (6) were characterized by crystallography. Low temperature solution and solid state (31)P{(1)H} NMR were used to demonstrate that the structure of RuCl(2)(P(2)P(3)(tBu)) (4) is probably analogous to that of RuCl(2)(PhP(2)P(2)(tBu)) (5) which had been structurally characterized.

  14. Evaluation of the Subscapularis Tendon Tears on 3T Magnetic Resonance Arthrography: Comparison of Diagnostic Performance of T1-Weighted Spectral Presaturation with Inversion-Recovery and T2-Weighted Turbo Spin-Echo Sequences.

    PubMed

    Lee, Hoseok; Ahn, Joong Mo; Kang, Yusuhn; Oh, Joo Han; Lee, Eugene; Lee, Joon Woo; Kang, Heung Sik

    2018-01-01

    To compare the T1-weighted spectral presaturation with inversion-recovery sequences (T1 SPIR) with T2-weighted turbo spin-echo sequences (T2 TSE) on 3T magnetic resonance arthrography (MRA) in the evaluation of the subscapularis (SSC) tendon tear with arthroscopic findings as the reference standard. This retrospective study included 120 consecutive patients who had undergone MRA within 3 months between April and December 2015. Two musculoskeletal radiologists blinded to the arthroscopic results evaluated T1 SPIR and T2 TSE images in separate sessions for the integrity of the SSC tendon, examining normal/articular-surface partial-thickness tear (PTTa)/full-thickness tear (FTT). Diagnostic performance of T1 SPIR and T2 TSE was calculated with arthroscopic results as the reference standard, and sensitivity, specificity, and accuracy were compared using the McNemar test. Interobserver agreement was measured with kappa (κ) statistics. There were 74 SSC tendon tears (36 PTTa and 38 FTT) confirmed by arthroscopy. Significant differences were found in the sensitivity and accuracy between T1 SPIR and T2 TSE using the McNemar test, with respective rates of 95.9-94.6% vs. 71.6-75.7% and 90.8-91.7% vs. 79.2-83.3% for detecting tear; 55.3% vs. 31.6-34.2% and 85.8% vs. 78.3-79.2%, respectively, for FTT; and 91.7-97.2% vs. 58.3-61.1% and 89% vs. 78-79.3%, respectively, for PTTa. Interobserver agreement for T1 SPIR was almost perfect for T1 SPIR (κ = 0.839) and substantial for T2 TSE (κ = 0.769). T1-weighted spectral presaturation with inversion-recovery sequences is more sensitive and accurate compared to T2 TSE in detecting SSC tendon tear on 3T MRA.

  15. T2 Mapping of the Sacroiliac Joints With 3-T MRI: A Preliminary Study.

    PubMed

    Lefebvre, Guillaume; Bergère, Antonin; Rafei, Mazen El; Duhamel, Alain; Teixeira, Pedro; Cotten, Anne

    2017-08-01

    The objective of this study was to assess the feasibility of T2 relaxation time measurements of the sacroiliac joints. The sacroiliac joints of 40 patients were imaged by 3-T MRI using an oblique axial multislice multiecho spin-echo T2-weighted sequence. Manual plotting and automatic subdivision of ROIs allowed us to obtain T2 values for up to 48 different areas per patient (posterior and anterior parts, sacral, intermediate, and iliac parts). Intraand interobserver reproducibility of T2 values were calculated after independent assessment by two musculoskeletal radiologists. A total of 1656 measurement sites could be analyzed. Mean (± SD) T2 values were 40.6 ± 6.7 ms and 41.2 ± 6.3 ms for observer 1 and 39.9 ± 6.6 ms for observer 2. The intraobserver intraclass correlation coefficient was 0.72 (95% CI, 0.70-0.74), and the interobserver intraclass correlation coefficient was 0.71 (95% CI, 0.68-0.72). Our study shows the feasibility of T2 relaxation time measurements at the sacroiliac joints.

  16. Early postnatal myelin content estimate of white matter via T1w/T2w ratio

    NASA Astrophysics Data System (ADS)

    Lee, Kevin; Cherel, Marie; Budin, Francois; Gilmore, John; Zaldarriaga Consing, Kirsten; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Glasser, Matthew F.; Van Essen, David C.; Buss, Claudia; Styner, Martin

    2015-03-01

    To develop and evaluate a novel processing framework for the relative quantification of myelin content in cerebral white matter (WM) regions from brain MRI data via a computed ratio of T1 to T2 weighted intensity values. We employed high resolution (1mm3 isotropic) T1 and T2 weighted MRI from 46 (28 male, 18 female) neonate subjects (typically developing controls) scanned on a Siemens Tim Trio 3T at UC Irvine. We developed a novel, yet relatively straightforward image processing framework for WM myelin content estimation based on earlier work by Glasser, et al. We first co-register the structural MRI data to correct for motion. Then, background areas are masked out via a joint T1w and T2 foreground mask computed. Raw T1w/T2w-ratios images are computed next. For purpose of calibration across subjects, we first coarsely segment the fat-rich facial regions via an atlas co-registration. Linear intensity rescaling based on median T1w/T2w-ratio values in those facial regions yields calibrated T1w/T2wratio images. Mean values in lobar regions are evaluated using standard statistical analysis to investigate their interaction with age at scan. Several lobes have strongly positive significant interactions of age at scan with the computed T1w/T2w-ratio. Most regions do not show sex effects. A few regions show no measurable effects of change in myelin content change within the first few weeks of postnatal development, such as cingulate and CC areas, which we attribute to sample size and measurement variability. We developed and evaluated a novel way to estimate white matter myelin content for use in studies of brain white matter development.

  17. Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsui, Keiji; Oda, Kasumi; Mizuta, Shumpei

    2013-10-11

    Highlights: •MED1 is a bona fide T3-dependent coactivator on TSHB promoter. •Mice with LxxLL-mutant MED1 have attenuated TSHβ mRNA and thyroid hormone levels. •MED1 activates TSHB promoter T3-dependently in cultured cells. •T3-dependent MED1 action is enhanced when SRC1/SRC2 or HDAC2 is downregulated. •MED1 is also a T3-independent GATA2/Pit1 coactivator on TSHB promoter. -- Abstract: The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor β (TRβ) on the TSHβmore » gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHβ gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHβ gene promoter.« less

  18. Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

    PubMed

    Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

    2018-01-01

    Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

  19. Biochemical evaluation of articular cartilage in patients with osteochondrosis dissecans by means of quantitative T2- and T2-mapping at 3T MRI: a feasibility study.

    PubMed

    Marik, W; Apprich, S; Welsch, G H; Mamisch, T C; Trattnig, S

    2012-05-01

    To perform an in vivo evaluation comparing overlying articular cartilage in patients suffering from osteochondrosis dissecans (OCD) in the talocrural joint and healthy volunteers using quantitative T2 mapping at 3.0 T. Ten patients with OCD of Grade II or lower and 9 healthy age matched volunteers were examined at a 3.0 T whole body MR scanner using a flexible multi-element coil. In all investigated persons MRI included proton-density (PD)-FSE and 3D GRE (TrueFisp) sequences for morphological diagnosis and location of anatomical site and quantitative T2 and T2 maps. Region of interest (ROI) analysis was performed for the cartilage layer above the OCD and for a morphologically healthy graded cartilage layer. Mean T2 and T2 values were then statistically analysed. The cartilage layer of healthy volunteers showed mean T2 and T2 values of 29.4 ms (SD 4.9) and 11.8 ms (SD 2.7), respectively. In patients with OCD of grade I and II lesions mean T2 values were 40.9 ms (SD 6.6), 48.7 ms (SD 11.2) and mean T2 values were 16.1 ms (SD 3.2), 16.2 ms (SD 4.8). Therefore statistically significantly higher mean T2 and T2 values were found in patients suffering from OCD compared to healthy volunteers. T2 and T2 mapping can help assess the microstructural composition of cartilage overlying osteochondral lesions. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Distinct Contributions of T1R2 and T1R3 Taste Receptor Subunits to the Detection of Sweet Stimuli

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nie,Y.; Vigues, S.; Hobbs, J.

    2005-01-01

    The molecular mechanisms by which G protein-coupled receptor (GPCR)-type chemosensory receptors of animals selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes, though little is known about the relative contributions of individual subunits to receptor functions. This study showed that each of the two subunits in the mammalian heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli, though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in mice.more » Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.« less

  1. A comparison study between 3D T2-weighted SPACE and conventional 2D T2-weighted turbo spin echo in assessment of carotid plaque.

    PubMed

    Lv, Peng; Dai, Yuanyuan; Lin, Jiang; Zhang, Weisheng; Liu, Hao; Liu, Hui; Tang, Xiao

    2017-03-01

    The aim of this study was to compare 3D T2-weighted sampling perfection with application optimized contrast using different flip angle evolutions (T2w SPACE) with conventional 2D T2w turbo-spin echo (TSE) in plaque imaging of carotid artery. 45 patients underwent 3.0-T MRI for carotid arteries imaging. MR sequences included T2w SPACE, T2w TSE, Time of flight (TOF) and T1-weighted (T1w) TSE. The signal intensity of intra-plaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and loose matrix (LM) were measured and their contrast ratios (CRs) against adjacent muscle were calculated. CRs from T2w SPACE and T2w TSE were compared to each other. CRs of LM, LRNC, and IPH measured on T2w SPACE were 1.74-3.04 (2.44), 0.98-1.66 (1.39), and 1.91-2.93 (2.51), respectively. CRs of LM, LRNC, and IPH on T2w TSE were 1.97-3.41 (2.44), 1.18-1.73 (1.43), and 2.26-3.75 (2.26), respectively. There was no significant difference of CR of the carotid plaques between T2w SPACE and T2w TSE (p = 0.455). Markedly significant differences of CRs were found between LM and LRNC (p < 0.001), and between LRNC and IPH (p < 0.001) on T2w SPACE and T2w TSE. T2w SPACE was comparable with conventional T2w TSE in characterization of carotid plaque.

  2. Three-dimensional quantitative T1 and T2 mapping of the carotid artery: Sequence design and in vivo feasibility.

    PubMed

    Coolen, Bram F; Poot, Dirk H J; Liem, Madieke I; Smits, Loek P; Gao, Shan; Kotek, Gyula; Klein, Stefan; Nederveen, Aart J

    2016-03-01

    A novel three-dimensional (3D) T1 and T2 mapping protocol for the carotid artery is presented. A 3D black-blood imaging sequence was adapted allowing carotid T1 and T2 mapping using multiple flip angles and echo time (TE) preparation times. B1 mapping was performed to correct for spatially varying deviations from the nominal flip angle. The protocol was optimized using simulations and phantom experiments. In vivo scans were performed on six healthy volunteers in two sessions, and in a patient with advanced atherosclerosis. Compensation for patient motion was achieved by 3D registration of the inter/intrasession scans. Subsequently, T1 and T2 maps were obtained by maximum likelihood estimation. Simulations and phantom experiments showed that the bias in T1 and T2 estimation was < 10% within the range of physiological values. In vivo T1 and T2 values for carotid vessel wall were 844 ± 96 and 39 ± 5 ms, with good repeatability across scans. Patient data revealed altered T1 and T2 values in regions of atherosclerotic plaque. The 3D T1 and T2 mapping of the carotid artery is feasible using variable flip angle and variable TE preparation acquisitions. We foresee application of this technique for plaque characterization and monitoring plaque progression in atherosclerotic patients. © 2015 Wiley Periodicals, Inc.

  3. Characterization of Fe3O4/SiO2/Gd2O(CO3)2 core/shell/shell nanoparticles as T1 and T2 dual mode MRI contrast agent.

    PubMed

    Yang, Meicheng; Gao, Lipeng; Liu, Kai; Luo, Chunhua; Wang, Yiting; Yu, Lei; Peng, Hui; Zhang, Wen

    2015-01-01

    Core/shell/shell structured Fe3O4/SiO2/Gd2O(CO3)2 nanoparticles were successfully synthesized. Their properties as a new type of T1-T2 dual model contrast agent for magnetic resonance imaging were investigated. Due to the introduce of a separating SiO2 layer, the magnetic coupling between Gd2O(CO3)2 and Fe3O4 could be modulated by the thickness of SiO2 layer and produce appropriate T1 and T2 signal. Additionally, the existence of Gd(3+) enhances the transverse relaxivity of Fe3O4 possibly because of the magnetic coupling between Gd(3+) and Fe3O4. The Fe3O4/SiO2/Gd2O(CO3)2 nanoparticles exhibit good biocompatibility, showing great potential for biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice

    PubMed Central

    Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F.; Vasselli, Joseph R.; Sclafani, Anthony

    2015-01-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. PMID:26157055

  5. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

    PubMed

    Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

    2015-09-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. Copyright © 2015 the American Physiological Society.

  6. Thy-1+ dendritic epidermal cells express T3 antigen and the T-cell receptor gamma chain.

    PubMed Central

    Stingl, G; Koning, F; Yamada, H; Yokoyama, W M; Tschachler, E; Bluestone, J A; Steiner, G; Samelson, L E; Lew, A M; Coligan, J E

    1987-01-01

    The murine epidermis is a heterogeneous epithelium composed of keratinocytes, melanocytes, Langerhans cells, and a recently described subpopulation (2-3%) of bone-marrow-derived leukocytes with a dendritic morphology and the cell surface phenotype Thy-1+, L3T4-, Lyt-2-. Previous studies have demonstrated that cell lines derived from freshly explanted Thy-1+ dendritic epidermal cells (DEC) have abundant mRNA for rearranged T-cell receptor (TCR) gamma-chain genes. Analysis of Thy-1+ DEC in situ, freshly isolated cell suspensions of Thy-1+ DEC, and long-term Thy-1+ DEC lines demonstrated that 100% of the Thy-1+ DEC reacted with a monoclonal antibody to the epsilon chain of the murine T3 complex and that 40-60% of resident Thy-1+ DEC were also reactive with an antiserum to the TCR gamma chain. Two Thy-1+ DEC lines expressed a disulfide-linked 70-kDa molecule that could be precipitated with an anti-gamma-chain antiserum and could be coprecipitated with an antiserum to the T3 delta chain; the molecule appeared as a single 34-kDa band under reducing conditions. The phenotype of Thy-1+ DEC (T3+, L3T4-, Lyt-2-, TCR gamma chain+) thus resembles that of the recently described subpopulation of murine and human lymphocytes that have been identified in the thymus, peripheral blood, and fetal blood. Images PMID:2885839

  7. Spatial Distribution and Relationship of T1ρ and T2 Relaxation Times in Knee Cartilage With Osteoarthritis

    PubMed Central

    Li, Xiaojuan; Pai, Alex; Blumenkrantz, Gabrielle; Carballido-Gamio, Julio; Link, Thomas; Ma, Benjamin; Ries, Michael; Majumdar, Sharmila

    2009-01-01

    T1ρ and T2 relaxation time constants have been proposed to probe biochemical changes in osteoarthritic cartilage. This study aimed to evaluate the spatial correlation and distribution of T1ρ and T2 values in osteoarthritic cartilage. Ten patients with osteoarthritis (OA) and 10 controls were studied at 3T. The spatial correlation of T1ρ and T2 values was investigated using Z-scores. The spatial variation of T1ρ and T2 values in patellar cartilage was studied in different cartilage layers. The distribution of these relaxation time constants was measured using texture analysis parameters based on gray-level co-occurrence matrices (GLCM). The mean Z-scores for T1ρ and T2 values were significantly higher in OA patients vs. controls (P < 0.05). Regional correlation coefficients of T1ρ and T2 Z-scores showed a large range in both controls and OA patients (0.2– 0.7). OA patients had significantly greater GLCM contrast and entropy of T1ρ values than controls (P < 0.05). In summary, T1ρ and T2 values are not only increased but are also more heterogeneous in osteoarthritic cartilage. T1ρ and T2 values show different spatial distributions and may provide complementary information regarding cartilage degeneration in OA. PMID:19319904

  8. White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

    PubMed

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  9. White matter fiber-based analysis of T1w/T2w ratio map

    NASA Astrophysics Data System (ADS)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  10. Hybridized 1T/2H MoS2 Having Controlled 1T Concentrations and its use in Supercapacitors.

    PubMed

    Thi Xuyen, Nguyen; Ting, Jyh-Ming

    2017-12-06

    Molybdenum disulfide (MoS 2 ) nanoflowers consisting of hybridized 1T/2H phases have been synthesized by using a microwave-assisted hydrothermal (MTH) method. The concentration of the 1T phase, ranging from 40 % to 73 %, is controlled by simply adjusting the ratio of the Mo and S precursors. By using the hybridized 1T/2H MoS 2 as an electrode material, it was demonstrated that the resulting supercapacitor performance is dominated by the 1T phase concentration. It was found that a supercapacitor with 73 % 1T phase exhibits excellent capacitance of 259 F g -1 and great cyclic stability after 1000 cycles. The formation mechanism of the MHT-synthesized hybridized 1T/2H MoS 2 is also reported. More importantly, the mechanism also explains the observed relationship between the 1T phase concentration and the ratio of the Mo and S precursors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Effects of potassium iodide in concentrations of TSH, tT3 and tT4 in serum of subjects with sporotrichosis.

    PubMed

    Ramírez Soto, Max Carlos

    2014-08-01

    The saturated potassium iodide solution (SSKI) as treatment for sporotrichosis may cause hypothyroidism by suppressing the synthesis of thyroid hormones (tT3 and tT4 ) and the iodine excess could lead to thyrotoxicosis. Evaluating the changes in serum levels of TSH, tT3 and tT4 in euthyroid patients with sporotrichosis treated with SSKI. For the selection of euthyroid patients, TSH, tT3 and tT4 concentrations were measured for those adults and children diagnosed with sporotrichosis. Each paediatric patient was administered SSKI orally in increasing doses of 2-20 drops/3 times/day and 4-40 drops/3 times/day in adults. Serum concentrations of TSH, tT3 and tT4 were measured 20 days after started the treatment and 15 days posttreatment. Eight euthyroid patients aged between 2 to 65 years old were included. After 20 days of treatment, two suffered subclinical hypothyroidism, one developed subclinical hyperthyroidism, and one hyperthyroxinaemia euthyroid. At 15 days posttreatment only four patients were evaluated and all serum levels of TSH, tT3 and tT4 were normal. Some euthyroid patients with sporotrichosis can develop hyperthyroidism or subclinical iodine-induced hypothyroidism, during the administration of 3 or 6 g SSKI/day. © 2014 Blackwell Verlag GmbH.

  12. Cytosolic T3-binding protein modulates dynamic alteration of T3-mediated gene expression in cells.

    PubMed

    Takeshige, Keiko; Sekido, Takashi; Kitahara, Jun-ichirou; Ohkubo, Yousuke; Hiwatashi, Dai; Ishii, Hiroaki; Nishio, Shin-ichi; Takeda, Teiji; Komatsu, Mitsuhisa; Suzuki, Satoru

    2014-01-01

    μ-Crystallin (CRYM) is also known as NADPH-dependent cytosolic T3-binding protein. A study using CRYM-null mice suggested that CRYM stores triiodothyronine (T3) in tissues. We previously established CRYM-expressing cells derived from parental GH3 cells. To examine the precise regulation of T3-responsive genes in the presence of CRYM, we evaluated serial alterations of T3-responsive gene expression by changing pericellular T3 concentrations in the media. We estimated the constitutive expression of three T3-responsive genes, growth hormone (GH), deiodinase 1 (Dio1), and deiodinase 2 (Dio2), in two cell lines. Subsequently, we measured the responsiveness of these three genes at 4, 8, 16, and 24 h after adding various concentrations of T3. We also estimated the levels of these mRNAs 24 and 48 h after removing T3. The levels of constitutive expression of GH and Dio1 were low and high in C8 cells, respectively, while Dio2 expression was not significantly different between GH3 and C8 cells. When treated with T3, Dio2 expression was significantly enhanced in C8 cells, while there were no differences in GH or Dio1 expression between GH3 and C8 cell lines. In contrast, removal of T3 retained the mRNA expression of GH and Dio2 in C8 cells. These results suggest that CRYM expression increases and sustains the T3 responsiveness of genes in cells, especially with alteration of the pericellular T3 concentration. The heterogeneity of T3-related gene expression is dependent on cellular CRYM expression in cases of dynamic changes in pericellular T3 concentration.

  13. The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd-DOTA-peptides.

    PubMed

    Cao, Limin; Li, Binbin; Yi, Peiwei; Zhang, Hailu; Dai, Jianwu; Tan, Bo; Deng, Zongwu

    2014-04-01

    Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T1 contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T1 relaxation rate which is in favor of T1-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T1 contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T1 contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T1 contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T1 contrast enhancement effect is discussed. Our results suggest that T1 contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T1-relaxation and T2-relaxation processes/rates. Both T1 and particularly T2 relaxation rate have to be taken into account to interpret T1 contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering

    PubMed Central

    Yang, Yunzhi Peter

    2015-01-01

    Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies. PMID:26407291

  15. Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering.

    PubMed

    Ker, Dai Fei Elmer; Sharma, Rashmi; Wang, Evelyna Tsi Hsin; Yang, Yunzhi Peter

    2015-01-01

    Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies.

  16. Fast T2*-weighted MRI of the prostate at 3 Tesla.

    PubMed

    Hardman, Rulon L; El-Merhi, Fadi; Jung, Adam J; Ware, Steve; Thompson, Ian M; Friel, Harry T; Peng, Qi

    2011-04-01

    To describe a rapid T2*-weighted (T2*W), three-dimensional (3D) echo planar imaging (EPI) sequence and its application in mapping local magnetic susceptibility variations in 3 Tesla (T) prostate MRI. To compare the sensitivity of T2*W EPI with routinely used T1-weighted turbo-spin echo sequence (T1W TSE) in detecting hemorrhage and the implications on sequences sensitive to field inhomogeneities such as MR spectroscopy (MRS). B(0) susceptibility weighted mapping was performed using a 3D EPI sequence featuring a 2D spatial excitation pulse with gradients of spiral k-space trajectory. A series of 11 subjects were imaged using 3T MRI and combination endorectal (ER) and six-channel phased array cardiac coils. T1W TSE and T2*W EPI sequences were analyzed quantitatively for hemorrhage contrast. Point resolved spectroscopy (PRESS MRS) was performed and data quality was analyzed. Two types of susceptibility variation were identified: hemorrhagic and nonhemorrhagic T2*W-positive areas. Post-biopsy hemorrhage lesions showed on average five times greater contrast on the T2*W images than T1W TSE images. Six nonhemorrhage regions of severe susceptibility artifact were apparent on the T2*W images that were not seen on standard T1W or T2W images. All nonhemorrhagic susceptibility artifact regions demonstrated compromised spectral quality on 3D MRS. The fast T2*W EPI sequence identifies hemorrhagic and nonhemorrhagic areas of susceptibility variation that may be helpful in prostate MRI planning at 3.0T. Copyright © 2011 Wiley-Liss, Inc.

  17. Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

    PubMed

    Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

    2014-01-01

    To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  18. Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

    PubMed

    Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

    2017-09-01

    To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P < 0.001). The Michelson Contrast equation showed that contrast differences between these two regions for the ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P < 0.001). Finally, the ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

  19. Effect of 3,5,3'-Triiodothyronine (T3) administration on dio1 gene expression and T3 metabolism in normal and type 1 deiodinase-deficient mice.

    PubMed

    Maia, A L; Kieffer, J D; Harney, J W; Larsen, P R

    1995-11-01

    The type 1 deiodinase (D1) catalyzes the monodeiodination of T4 to produce T3, the active thyroid hormone. In the C3H mouse, hepatic D1 and the dio1 messenger RNA (mRNA) are only 10% that in the C57 strain, the common phenotype. Low activity cosegregated with a series of five GCT repeats located in the 5'-flanking region of the C3H dio1 gene that impaired C3H promoter potency and provided a partial explanation for the lower D1. The present studies were performed to search for additional explanations for low D1 activity in C3H mice. Previous studies have shown that T3 up-regulates the dio1 gene. Therefore, loss of the capacity to respond to endogenous T3 is a possible additional cause of the lower D1 levels in the C3H mice. The hepatic C3H dio1 mRNA increases 10- to 20 fold after T3 administration. The t3 effect occurs at a transplantation level and T3 does not alter the dio1 mRNA half-life. Despite the transcriptional response to T3, no functional thyroid response elements were identified in the 1.5-kilobase 5'-flanking region of either the C57 or C3H dio1 gene. After the same dose of exogenous T3, both dio1 mRNA and D1 of the C3H mouse respond to a greater extent than those of the C57 strain. This can be explained in part by the reduction in T3 clearance due to the lower D1 levels in C3H mice in which higher concentrations of circulating T3 are maintained. The decrease in serum T3 levels and T3 production observed in fasting and systemic illness in both human and experimental animals has been attributed in part to a decrease in hepatic D1. In contrast, despite markedly lower hepatic and renal D1 levels, serum T3 concentrations remain normal in C3H mice. The present studies suggest that the absence of stress-induced hypothalamic-pituitary suppression that allows T4 production to be maintained together with the reduced clearance of T3 and T4 via inner ring deiodination compensate for the D1 deficiency.

  20. APOC3 Promoter Polymorphisms C-482T and T-455C Are Associated with the Metabolic Syndrome1

    PubMed Central

    Miller, Michael; Rhyne, Jeffrey; Chen, Hegang; Beach, Valerie; Ericson, Richard; Luthra, Kalpana; Dwivedi, Manjari; Misra, Anoop

    2007-01-01

    Background Despite the growing epidemic of the metabolic syndrome (MetS), few studies have evaluated genetic polymorphisms associated with the MetS phenotype. One candidate, APOC3, modulates lipid and lipoprotein metabolism and the promoter polymorphisms C-482T/T-455C are associated with loss of insulin downregulation. Methods One hundred twenty two consecutive MetS cases were matched by age, sex and race in a 1:1 case-control design to evaluate the prevalence of common polymorphisms in the following candidate genes: APOC3, APOE, B3AR, FABP2, GNB3, LPL, and PPARα and PPARγ. Results Compared to controls, MetS subjects exhibited a greater prevalence of APOC3 promoter polymorphisms. Specifically, the frequency of the variant C-482T and T-455C alleles was 70.5 and 81.9% of cases compared to 43.4 and 54.1% in controls, respectively ( p <0.0001). Overall, APOC3 promoter variants were associated with a greater likelihood of MetS compared to wild type [C-482T (OR: 4.3; 95% CI: 2.2, 8.6 [p <0.0001]), T-455C (OR: 3.6; 95% CI: 2.0, 6.7 [p <0.0001])]. No material differences were identified between the other genetic variants tested and prevalence of MetS. Conclusions These data, therefore, suggest that the APOC3 promoter polymorphisms C-482T and T-455C are associated with the MetS. PMID:17416293

  1. Can standard anterior Smith-Robinson supramanubrial approach be utilized for approach down to T2 or T3?

    PubMed

    Singhatanadgige, Weerasak; Zebala, Lukas P; Luksanapruksa, Panya; Daniel Riew, K

    2017-09-01

    The aim of this study was to determine a plain radiographic criterion for determining the feasibility of using the standard anterior Smith-Robinson supramanubrial approach for anterior surgery down to T2 or T3. The surgical database (2002-2014) was searched to identify patients with anterior cervical surgery to T2 or T3. A method to determine whether a standard anterior Smith-Robinson approach can be used to operate on the upper thoracic levels was evaluated. The surgeon chose the surgical approach preoperatively using a lateral radiograph by determining if a line from the intended skin incision to the lower instrumented level (LIV) passed above the top of the manubrium. If so, a standard Smith-Robinson approach was selected. Another spine surgeon then analyzed all patients who had anterior thoracic fusion to T2 or below. The lateral radiographs were retrospectively reviewed. A total of 44 patients who underwent anterior surgery down to T2 or T3 vertebrae were identified. T2 was the LIV in 39 patients. T3 was the LIV in five patients. No surgery was abandoned or converted to a difference approach after making the standard Smith-Robinson approach. To increase visualization, T1 corpectomy was necessary in 4 of 39 patients when T2 was the LIV. T2 corpectomy was necessary in 2 of 5 patients when T3 was the LIV. If a line from the intended skin incision to the LIV passes over the top of the manubrium, a standard Smith-Robinson approach without sternotomy can be successfully used.

  2. Hybrid nanotrimers for dual T 1 and T 2-weighted magnetic resonance imaging

    DOE PAGES

    Cheng, Kai; Yang, Meng; Zhang, Ruiping; ...

    2014-10-04

    Development of multifunctional nanoparticle-based probes for dual T 1- and T 2-weighted magnetic resonance imaging (MRI) could allow us to image and diagnose the tumors or other abnormalities in an exceptionally accurate and reliable manner. In this study, by fusing distinct nanocrystals via solid-state interfaces, we built hybrid heteronanostructures to combine both T 1 and T 2- weighted contrast agents together for MRI with high accuracy and reliability. The resultant hybrid heterotrimers showed high stability in physiological conditions and could induce both simultaneous positive and negative contrast enhancements in MR images. Small animal positron emission tomography imaging study revealed thatmore » the hybrid heterostructures displayed favorable biodistribution and were suitable for in vivo imaging. Furthermore, their potential as dual contrast agents for T 1 and T 2-weighted MRI was further demonstrated by in vitro and in vivo imaging and relaxivity measurements.« less

  3. Whole brain myelin mapping using T1- and T2-weighted MR imaging data

    PubMed Central

    Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

    2014-01-01

    Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approach is a retrospective calibration algorithm, applied to bias-corrected T1-w and T2-w images, that relies on image intensities outside the brain. This permits standardizing the intensity histogram of the ratio image, thereby allowing for across-subject statistical analyses. Quantitative comparisons of image histograms within and across different datasets confirmed the effectiveness of our normalization procedure. Not only did the calibrated T1-w/T2-w images exhibit a comparable intensity range, but also the shape of the intensity histograms was largely corresponding. We also assessed the reliability and specificity of the ratio image compared to other MR-based techniques, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), and fluid-attenuated inversion recovery (FLAIR). With respect to these other techniques, T1-w/T2-w had consistently high values, as well as low inter-subject variability, in brain structures where myelin is most abundant. Overall, our results suggested that the T1-w/T2-w technique may be a valid tool supporting the non-invasive mapping of myelin in the brain. Therefore, it might find important applications in the study of brain development, aging and disease. PMID:25228871

  4. Signal-to-noise ratio, T2 , and T2* for hyperpolarized helium-3 MRI of the human lung at three magnetic field strengths.

    PubMed

    Komlosi, Peter; Altes, Talissa A; Qing, Kun; Mooney, Karen E; Miller, G Wilson; Mata, Jaime F; de Lange, Eduard E; Tobias, William A; Cates, Gordon D; Mugler, John P

    2017-10-01

    To evaluate T 2 , T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 ( 3 He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T. Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T 2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3 He dose. As expected, T 2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3 He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant. Hyperpolarized 3 He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T 2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med 78:1458-1463, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  5. A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance-the T1 Mapping and ECV Standardization in cardiovascular magnetic resonance (T1MES) program.

    PubMed

    Captur, Gabriella; Gatehouse, Peter; Keenan, Kathryn E; Heslinga, Friso G; Bruehl, Ruediger; Prothmann, Marcel; Graves, Martin J; Eames, Richard J; Torlasco, Camilla; Benedetti, Giulia; Donovan, Jacqueline; Ittermann, Bernd; Boubertakh, Redha; Bathgate, Andrew; Royet, Celine; Pang, Wenjie; Nezafat, Reza; Salerno, Michael; Kellman, Peter; Moon, James C

    2016-09-22

    T 1 mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T 1 mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T 1 and T 2 in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformité Européene (CE) marking. The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently-doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T 1 maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the B 1 field. T 1 and T 2 values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15-30 °C the short-T 1 tubes were more stable with temperature than the long-T 1 tubes. A batch of 69 phantoms was mass-produced with random sampling of

  6. Comparison of only T3 and T3T4 sympathectomy for axillary hyperhidrosis regarding treatment effect and compensatory sweating

    PubMed Central

    Yuncu, Gökhan; Turk, Figen; Ozturk, Gökhan; Atinkaya, Cansel

    2013-01-01

    OBJECTIVES Patients diagnosed with axillary hyperhidrosis can face psychosocial issues that can ultimately hinder their quality of life both privately and socially. The routine treatment for axillary hyperhidrosis is T3T4 sympathectomy, but compensatory sweating is a serious side effect that is commonly seen with this approach. This study was designed to evaluate whether a T3 sympathectomy was effective for the treatment of axillary hyperhidrosis and whether this treatment led to less compensatory sweating than T3T4 sympathectomies among our 60-patient population. METHODS One hundred and twenty endoscopic thoracic sympathectomies were performed on 60 patients who had axillary hyperhidrosis. The sympathectomies were accomplished by means of a single-lumen endotracheal tube and a single port. The axillary hyperhidrosis patients were randomly divided into two groups with 17 patients in Group 1 undergoing T3T4 sympathectomies and 43 in Group 2 undergoing only T3 sympathectomies. We analysed the data associated with the resolution of axillary hyperhidrosis, the degree of patient satisfaction with the surgical outcome and the quality of life in parallel with compensatory sweating after the procedure as reported by the patient and confirmed by the examiner. Moreover, the results were compared statistically. RESULTS No statistically significant difference was observed between the groups based on age (P = 0.56), gender (P = 0.81), duration of the surgery (P = 0.35) or postoperative satisfaction levels (P = 0.45). However, the incidence and degree of compensatory sweating were lower in the T3 group than the T3T4 group at the 1-year follow-up (P = 0.008). CONCLUSIONS T3 sympathectomy was as effective as T3T4 sympathectomy for the treatment of axillary hyperhidrosis based on the patients’ reported postoperative satisfaction, and the T3 group demonstrated lower compensatory sweating at the 1-year follow-up. PMID:23644731

  7. The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging

    PubMed Central

    Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

    2016-01-01

    Objective: To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0 T in young healthy adults. Methods: 30 healthy male adults (18–31 years) who perform sports at an amateur level underwent an initial MRI at 3.0 T with T2 weighted [16 echo times (TEs): 9.7–154.6 ms] and T2* weighted (24 TEs: 4.6–53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product–moment correlation coefficients and confidence intervals were computed. Results: Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. Conclusion: A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. Advances in knowledge: This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults. PMID:27336705

  8. The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging.

    PubMed

    Behzadi, Cyrus; Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

    2016-08-01

    To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0 T in young healthy adults. 30 healthy male adults (18-31 years) who perform sports at an amateur level underwent an initial MRI at 3.0 T with T2 weighted [16 echo times (TEs): 9.7-154.6 ms] and T2* weighted (24 TEs: 4.6-53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product-moment correlation coefficients and confidence intervals were computed. Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults.

  9. Magnetic resonance evaluation of cardiac thrombi and masses by T1 and T2 mapping: an observational study.

    PubMed

    Caspar, Thibault; El Ghannudi, Soraya; Ohana, Mickaël; Labani, Aïssam; Lawson, Aubrietia; Ohlmann, Patrick; Morel, Olivier; De Mathelin, Michel; Roy, Catherine; Gangi, Afshin; Germain, Philippe

    2017-04-01

    The purpose of this work was to evaluate CMR T1 and T2 mapping sequences in patients with intracardiac thrombi and masses in order to assess T1 and T2 relaxometry usefulness and to allow better etiological diagnosis. This observational study of patients scheduled for routine CMR was performed from September 2014 to August 2015. All patients referred to our department for a 1.5 T CMR were screened to participate. T1 mapping were acquired before and after Gadolinium injection; T2 mapping images were obtained before injection. 41 patients were included. 22 presented with cardiac thrombi and 19 with cardiac masses. The native T1 of thrombi was 1037 ± 152 ms (vs 1032 ± 39 ms for myocardium, p = 0.88; vs 1565 ± 88 ms for blood pool, p < 0.0001). T2 were 74 ± 13 ms (vs 51 ± 3 ms for myocardium, p < 0.0001; vs 170 ± 32 ms for blood pool, p < 0.0001). Recent thrombi had a native T1 shorter than old thrombi (911 ± 177 vs 1169 ± 107 ms, p = 0.01). The masses having a shorter T1 than the myocardium were lipomas (278 ± 29 ms), calcifications (621 ± 218 ms), and melanoma (736 ms). All other masses showed T1 values higher than myocardial T1, with T2 consistently >70 ms. T1 and T2 mapping CMR sequences can be useful and represent a new approach for the evaluation of cardiac thrombi and masses.

  10. From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor.

    PubMed

    Morini, Gabriella; Bassoli, Angela; Temussi, Piero A

    2005-08-25

    The sweet taste receptor, a heterodimeric G protein coupled receptor (GPCR) protein, formed by the T1R2 and T1R3 subunits, recognizes several sweet compounds including carbohydrates, amino acids, peptides, proteins, and synthetic sweeteners. Its similarity with the metabotropic glutamate mGluR1 receptor allowed us to build homology models. All possible dimers formed by combinations of the human T1R2 and T1R3 subunits, modeled on the A (closed) or B (open) chains of the extracellular ligand binding domain of the mGluR1 template, yield four ligand binding sites for low-molecular-weight sweeteners. These sites were probed by docking a set of molecules representative of all classes of sweet compounds and calculating the free energy of ligand binding. These sites are not easily accessible to sweet proteins, but docking experiments in silico showed that sweet proteins can bind to a secondary site without entering the deep cleft. Our models account for many experimental observations on the tastes of sweeteners, including sweetness synergy, and can help to design new sweeteners.

  11. Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths

    PubMed Central

    West, Janne; Blystad, Ida; Engström, Maria; Warntjes, Jan B. M.; Lundberg, Peter

    2013-01-01

    Background Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. Methods In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. Results Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001). Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. Conclusions Most of the brain was identically classified at the two field strengths, although some regional differences were observed. PMID:24066153

  12. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis.

    PubMed

    Chae, Wook-Jin; Park, Jong-Hyun; Henegariu, Octavian; Yilmaz, Saliha; Hao, Liming; Bothwell, Alfred L M

    2017-10-01

    Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3 + regulatory T (Treg) cells use Dickkopf-1 (DKK-1) to regulate T-cell-mediated tolerance in the T-cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4 + T-cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymus-derived Treg cells showed a robust expression of DKK-1 but not in naive or effector CD4 T cells. DKK-1 expression in Foxp3 + Treg cells was further increased upon T-cell receptor stimulation in vitro and in vivo. Interestingly, Foxp3 + Treg cells expressed DKK-1 in the cell membrane and the functional inhibition of DKK-1 using DKK-1 monoclonal antibody abrogated the suppressor function of Foxp3 + Treg cells. DKK-1 expression was dependent on de novo protein synthesis and regulated by the mitogen-activated protein kinase pathway but not by the canonical Wnt pathway. Taken together, our results highlight membrane-bound DKK-1 as a novel Treg-derived mediator to maintain immunological tolerance in T-cell-mediated autoimmune colitis. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  13. Contrast-enhanced Magnetic Resonance Imaging of Pelvic Bone Metastases at 3.0 T: Comparison Between 3-dimensional T1-weighted CAIPIRINHA-VIBE Sequence and 2-dimensional T1-weighted Turbo Spin-Echo Sequence.

    PubMed

    Yoon, Min A; Hong, Suk-Joo; Lee, Kyu-Chong; Lee, Chang Hee

    2018-06-12

    This study aimed to compare 3-dimensional T1-weighted gradient-echo sequence (CAIPIRINHA-volumetric interpolated breath-hold examination [VIBE]) with 2-dimensional T1-weighted turbo spin-echo sequence for contrast-enhanced magnetic resonance imaging (MRI) of pelvic bone metastases at 3.0 T. Thirty-one contrast-enhanced MRIs of pelvic bone metastases were included. Two contrast-enhanced sequences were evaluated for the following parameters: overall image quality, sharpness of pelvic bone, iliac vessel clarity, artifact severity, and conspicuity and edge sharpness of the smallest metastases. Quantitative analysis was performed by calculating signal-to-noise ratio and contrast-to-noise ratio of the smallest metastases. Significant differences between the 2 sequences were assessed. CAIPIRINHA-VIBE had higher scores for overall image quality, pelvic bone sharpness, iliac vessel clarity, and edge sharpness of the metastatic lesions, and had less artifacts (all P < 0.05). There was no significant difference in conspicuity, signal-to-noise ratio, or contrast-to-noise ratio of the smallest metastases (P > 0.05). Our results suggest that CAIPIRINHA-VIBE may be superior to turbo spin-echo for contrast-enhanced MRI of pelvic bone metastases at 3.0 T.

  14. Europium-engineered iron oxide nanocubes with high T1 and T2 contrast abilities for MRI in living subjects

    NASA Astrophysics Data System (ADS)

    Yang, Lijiao; Zhou, Zijian; Liu, Hanyu; Wu, Changqiang; Zhang, Hui; Huang, Guoming; Ai, Hua; Gao, Jinhao

    2015-04-01

    Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver

  15. 26 CFR 1.7519-3T - Effective date (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Effective date (temporary). 1.7519-3T Section 1.7519-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES The Tax Court § 1.7519-3T Effective date (temporary). The provisions of §§ 1.7519-1T...

  16. Thermonuclear Reaction Rate of T(t,2n) α Measured in ICF Plasmas

    NASA Astrophysics Data System (ADS)

    Brune, C. R.; Casey, D. T.; Caggiano, J. A.; Hatarik, R.; McNabb, D. P.; Sayre, D. B.; Smalyuk, V. A.; Bacher, A. D.; Frenje, J. A.; Gatu-Johnson, M.; Zylstra, A. B.; Couder, M.

    2014-09-01

    Measurements of charged-particle reactivity have been performed in inertial confinement fusion experiments at the National Ignition Facility. Time-of-flight detectors were used to measure neutrons from the T(t,2n) and T(d,n) reactions produced by implosions with tritium-filled targets (0.1% deuterium). Along with the measured target fuel composition and reactant ion temperature, the well-known T(d,n) reactivity was used to convert the measured neutron yields into a T(t,2n) reactivity. The ion temperature was determined to be 3.3(3) keV, corresponding to an effective energy of 16 keV. In comparison to accelerator measurements of the low-energy T(t,2n) cross section, the source of all previous data, our experiment has resulted in T(t,2n) data with better statistics and lower backgrounds.

  17. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells.

    PubMed

    Arbore, Giuseppina; West, Erin E; Spolski, Rosanne; Robertson, Avril A B; Klos, Andreas; Rheinheimer, Claudia; Dutow, Pavel; Woodruff, Trent M; Yu, Zu Xi; O'Neill, Luke A; Coll, Rebecca C; Sher, Alan; Leonard, Warren J; Köhl, Jörg; Monk, Pete; Cooper, Matthew A; Arno, Matthew; Afzali, Behdad; Lachmann, Helen J; Cope, Andrew P; Mayer-Barber, Katrin D; Kemper, Claudia

    2016-06-17

    The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4(+) T cells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (T(H)1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to "innate immune cells" but is an integral component of normal adaptive T(H)1 responses. Copyright © 2016, American Association for the Advancement of Science.

  18. Large NLO corrections in t\\overline{t}{W}^{± } and t\\overline{t}t\\overline{t} hadroproduction from supposedly subleading EW contributions

    NASA Astrophysics Data System (ADS)

    Frederix, Rikkert; Pagani, Davide; Zaro, Marco

    2018-02-01

    We calculate the complete-NLO predictions for t\\overline{t}{W}^{± } and t\\overline{t}t\\overline{t} production in proton-proton collisions at 13 and 100 TeV. All the non-vanishing contributions of O({α}_s^i{α}^j) with i + j = 3 , 4 for t\\overline{t}{W}^{± } and i + j = 4 , 5 for t\\overline{t}t\\overline{t} are evaluated without any approximation. For t\\overline{t}{W}^{± } we find that, due to the presence of tW → tW scattering, at 13(100) TeV the O({α}_s{α}^3) contribution is about 12(70)% of the LO, i.e., it is larger than the so-called NLO EW corrections (the O({α}_s^2{α}^2) terms) and has opposite sign. In the case of t\\overline{t}t\\overline{t} production, large contributions from electroweak tt → tt scattering are already present at LO in the O({α}_s^3α ) and O({α}_s^2{α}^2) terms. For the same reason we find that both NLO terms of O({α}_s^4α ) , i.e., the NLO EW corrections, and O({α}_s^3{α}^2) are large (±15% of the LO) and their relative contributions strongly depend on the values of the renormalisation and factorisation scales. However, large accidental cancellations are present (away from the threshold region) between these two contributions. Moreover, the NLO corrections strongly depend on the kinematics and are particularly large at the threshold, where even the relative contribution from O({α}_s^2{α}^3) terms amounts to tens of percents.

  19. Individual T1-weighted/T2-weighted ratio brain networks: Small-worldness, hubs and modular organization

    NASA Astrophysics Data System (ADS)

    Wu, Huijun; Wang, Hao; Lü, Linyuan

    Applying network science to investigate the complex systems has become a hot topic. In neuroscience, understanding the architectures of complex brain networks was a vital issue. An enormous amount of evidence had supported the brain was cost/efficiency trade-off with small-worldness, hubness and modular organization through the functional MRI and structural MRI investigations. However, the T1-weighted/T2-weighted (T1w/T2w) ratio brain networks were mostly unexplored. Here, we utilized a KL divergence-based method to construct large-scale individual T1w/T2w ratio brain networks and investigated the underlying topological attributes of these networks. Our results supported that the T1w/T2w ratio brain networks were comprised of small-worldness, an exponentially truncated power-law degree distribution, frontal-parietal hubs and modular organization. Besides, there were significant positive correlations between the network metrics and fluid intelligence. Thus, the T1w/T2w ratio brain networks open a new avenue to understand the human brain and are a necessary supplement for future MRI studies.

  20. Abdominal applications of 3.0-T MR imaging: comparative review versus a 1.5-T system.

    PubMed

    Choi, Jin-Young; Kim, Myeong-Jin; Chung, Yong Eun; Kim, Ji Youn; Jones, Alun C; de Becker, Jan; van Cauteren, Marc

    2008-01-01

    With the development of dedicated receiver coils and increased gradient performance, 3.0-T magnetic resonance (MR) systems are gaining wider acceptance in clinical practice. The expected twofold increase in signal-to-noise ratio (SNR) compared with that of 1.5-T MR systems may help improve spatial resolution or increase temporal resolution when used with parallel acquisition techniques. Several issues must be considered when applying 3.0-T MR in the abdomen, including the alteration of the radiofrequency field and relaxation time, increase in energy deposition and susceptibility effects, and problems associated with motion artifacts. For the evaluation of liver lesions, higher SNR and greater resolution achieved with the 3.0-T system could translate into better detection of malignant lesions on T2-weighted images obtained with adjusted imaging parameters. For the evaluation of pancreatic and biliary diseases, high-resolution T2-weighted imaging using single-shot turbo spin-echo sequences is useful; improvement in SNR was noticeable on two-dimensional MR cholangiopancreatographic images. For the preoperative imaging of rectal cancer, a single-shot sequence is useful for dramatically decreasing imaging time while maintaining image quality. Substantial modification of examination protocols, with optimized imaging parameters and sequence designs along with ongoing development of hardware, could contribute to an increased role of the 3.0-T system for abdominal MR examinations.

  1. Comparison of T2, T1rho, and diffusion metrics in assessment of liver fibrosis in rats.

    PubMed

    Zhang, Hui; Yang, Qihua; Yu, Taihui; Chen, Xiaodong; Huang, Jingwen; Tan, Cui; Liang, Biling; Guo, Hua

    2017-03-01

    To evaluate the value of T 2 , T 1 rho, and diffusion metrics in assessment of liver fibrosis in rats. Liver fibrosis in a rat model (n = 72) was induced by injection of carbon tetrachloride (CCl 4 ) at 3T. T 2 , T 1 rho, and diffusion parameters (apparent diffusion coefficient (ADC), D true ) via spin echo (SE) diffusion-weighted imaging (DWI) and stimulated echo acquisition mode (STEAM) DWI with three diffusion times (DT: 80, 106, 186 msec) were obtained in surviving rats with hepatic fibrosis (n = 52) and controls (n = 8). Liver fibrosis stage (F0-F6) was identified based on pathological results using the traditional liver fibrosis staging method for rodents. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analysis were employed to determine the diagnostic accuracy. Mean T 2 , T 1 rho, ADC, and D true with DT = 186 msec correlated with the severity of fibrosis with r = 0.73, 0.83, -0.83, and -0.85 (all P < 0.001), respectively. The average areas under the ROC curve at different stages for T 1 rho and diffusion parameters (DT = 186 msec) were larger than those of T 2 and SE DWI (0.92, 0.92, and 0.92 vs. 0.86, 0.82, and 0.83). The corresponding average sensitivity and specificity for T 1 rho and diffusion parameters with a long DT were larger (89.35 and 88.90, 88.36 and 89.97, 90.16 and 87.13) than T 2 and SE DWI (90.28 and 79.93, 85.30 and 77.64, 78.21 and 82.41). The performances of T 1 rho and D true (DT = 186 msec) were comparable (average AUC: 0.92 and 0.92). Among the evaluated sequences, T 1 rho and STEAM DWI with a long DT may serve as superior imaging biomarkers for assessing liver fibrosis and monitoring disease severity. 1 J. Magn. Reson. Imaging 2017;45:741-750. © 2016 International Society for Magnetic Resonance in Medicine.

  2. Quantitative water content mapping at clinically relevant field strengths: a comparative study at 1.5 T and 3 T.

    PubMed

    Abbas, Zaheer; Gras, Vincent; Möllenhoff, Klaus; Oros-Peusquens, Ana-Maria; Shah, Nadim Joni

    2015-02-01

    Quantitative water content mapping in vivo using MRI is a very valuable technique to detect, monitor and understand diseases of the brain. At 1.5 T, this technology has already been successfully used, but it has only recently been applied at 3T because of significantly increased RF field inhomogeneity at the higher field strength. To validate the technology at 3T, we estimate and compare in vivo quantitative water content maps at 1.5 T and 3T obtained with a protocol proposed recently for 3T MRI. The proposed MRI protocol was applied on twenty healthy subjects at 1.5 T and 3T; the same post-processing algorithms were used to estimate the water content maps. The 1.5 T and 3T maps were subsequently aligned and compared on a voxel-by-voxel basis. Statistical analysis was performed to detect possible differences between the estimated 1.5 T and 3T water maps. Our analysis indicates that the water content values obtained at 1.5 T and 3T did not show significant systematic differences. On average the difference did not exceed the standard deviation of the water content at 1.5 T. Furthermore, the contrast-to-noise ratio (CNR) of the estimated water content map was increased at 3T by a factor of at least 1.5. Vulnerability to RF inhomogeneity increases dramatically with the increasing static magnetic field strength. However, using advanced corrections for the sensitivity profile of the MR coils, it is possible to preserve quantitative accuracy while benefiting from the increased CNR at the higher field strength. Indeed, there was no significant difference in the water content values obtained in the brain at 1.5 T and 3T. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Effects of B1 inhomogeneity correction for three-dimensional variable flip angle T1 measurements in hip dGEMRIC at 3 T and 1.5 T.

    PubMed

    Siversson, Carl; Chan, Jenny; Tiderius, Carl-Johan; Mamisch, Tallal Charles; Jellus, Vladimir; Svensson, Jonas; Kim, Young-Jo

    2012-06-01

    Delayed gadolinium-enhanced MRI of cartilage is a technique for studying the development of osteoarthritis using quantitative T(1) measurements. Three-dimensional variable flip angle is a promising method for performing such measurements rapidly, by using two successive spoiled gradient echo sequences with different excitation pulse flip angles. However, the three-dimensional variable flip angle method is very sensitive to inhomogeneities in the transmitted B(1) field in vivo. In this study, a method for correcting for such inhomogeneities, using an additional B(1) mapping spin-echo sequence, was evaluated. Phantom studies concluded that three-dimensional variable flip angle with B(1) correction calculates accurate T(1) values also in areas with high B(1) deviation. Retrospective analysis of in vivo hip delayed gadolinium-enhanced MRI of cartilage data from 40 subjects showed the difference between three-dimensional variable flip angle with and without B(1) correction to be generally two to three times higher at 3 T than at 1.5 T. In conclusion, the B(1) variations should always be taken into account, both at 1.5 T and at 3 T. Copyright © 2011 Wiley-Liss, Inc.

  4. Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

    NASA Technical Reports Server (NTRS)

    Yamaguchi, T.; Chattopadhyay, N.; Kifor, O.; Butters, R. R. Jr; Sugimoto, T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

    1998-01-01

    The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

  5. [Laser debulking surgery prior to radiotherapy for T1T2 carcinoma of the hypopharynx].

    PubMed

    Mori, K; Chijiwa, K; Umeno, H; Umeno, T; Sakamoto, K

    2000-09-01

    The local control rate for T1-T2 carcinomas of the hypopharynx is rather high whereas the overall survival rate is unsatisfactory, irrespective of treatment modalities. Radical radiotherapy has yielded a local control rate of 40-70% and an overall 5-year survival of 30-50%, while surgical treatment with or without postoperative radiotherapy has yielded a local control rate of 60-90% and an overall 5-year survival rate of 30-60%. Based on these reasons, for the patients with minor hypopharyngeal lesions, such as T1-T2 carcinomas, in the Kurume University Hospital radiotherapy has often been selected as a first choice instead of partial pharyngectomy. If the primary lesion is exophytic and has a large volume, laser debulking surgery has been employed prior to radiotherapy to improve the local control rate. The purpose of the present study is to describe the details of laser debulking surgery prior to radiotherapy (LDSR) for the treatment of T1-T2 carcinomas of the hypopharynx. In addition, the preliminary results for this treatment procedure will also be compared with the results of partial pharyngectomies preserving the larynx (PPPL) that were performed in the Kurume University Hospital. In this study 20 patients (T1: 4, T2: 16) who had undergone PPPL and 16 patients (T1: 4, T2: 12) who had undergone LDSR were included. For patients undergoing PPPL, the 5-year local control rate, 5-year larynx conservation rate and disease specific 5-year survival rate were 83.6%, 70.4%, and 75.0%, respectively, whereas for patients undergoing LDSR these were 87.1%, 93.8%, 87.5% respectively. Although the treatment outcomes by LDSR did not show a significant drastic improvement compared with those by PPPL, the quality of life of the patients undergoing LDSR was not aggravated. LDSR may thus be preferable to PPPL for selected cases of T1-T2 carcinomas of the hypopharynx.

  6. Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.

    PubMed

    Karur, Gauri R; Robison, Sean; Iwanochko, Robert M; Morel, Chantal F; Crean, Andrew M; Thavendiranathan, Paaladinesh; Nguyen, Elsie T; Mathur, Shobhit; Wasim, Syed; Hanneman, Kate

    2018-04-24

    Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P < .001]; 1192 msec ± 52 vs 1268 msec ± 55 [P < .001]; and 1221 msec ± 54 vs 1271 msec ± 37 [P = .001], respectively). A septal LV native T1 cutoff point of 1220 msec or lower distinguished AFD from HCM with sensitivity of 97%, specificity of 93%, and accuracy of 95%. Septal LV native T1 values differentiated AFD from HCM after adjustment for age, sex, and conventional imaging features (odds ratio, 0.94; 95% confidence interval: 0.91, 0.98; P = < .001). In a nested logistic regression model with age, sex, and conventional imaging features, model fit was significantly improved by the addition of septal LV native T1 values (χ 2 [df = 1] = 33.4; P < .001). Conclusion Cardiac MR imaging native T1 values at 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic

  7. Non-water-suppressed 1 H FID-MRSI at 3T and 9.4T.

    PubMed

    Chang, Paul; Nassirpour, Sahar; Avdievitch, Nikolai; Henning, Anke

    2018-08-01

    This study investigates metabolite concentrations using metabolite-cycled 1 H free induction decay (FID) magnetic resonance spectroscopic imaging (MRSI) at ultra-high fields. A non-lipid-suppressed and slice-selective ultra-short echo time (TE) 1 H FID MRSI sequence was combined with a low-specific absorption rate (SAR) asymmetric inversion adiabatic pulse to enable non-water-suppressed metabolite mapping using metabolite-cycling at 9.4T. The results were compared to a water-suppressed FID MRSI sequence, and the same study was performed at 3T for comparison. The scan times for performing single-slice metabolite mapping with a nominal voxel size of 0.4 mL were 14 and 17.5 min on 3T and 9.4T, respectively. The low-SAR asymmetric inversion adiabatic pulse enabled reliable non-water-suppressed metabolite mapping using metabolite cycling at both 3T and 9.4T. The spectra and maps showed good agreement with the water-suppressed FID MRSI ones at both field strengths. A quantitative analysis of metabolite ratios with respect to N-acetyl aspartate (NAA) was performed. The difference in Cre/NAA was statistically significant, ∼0.1 higher for the non-water-suppressed case than for water suppression (from 0.73 to 0.64 at 3T and from 0.69 to 0.59 at 9.4T). The difference is likely because of chemical exchange effects of the water suppression pulses. Small differences in mI/NAA were also statistically significant, however, are they are less reliable because the metabolite peaks are close to the water peak that may be affected by the water suppression pulses or metabolite-cycling inversion pulse. We showed the first implementation of non-water-suppressed metabolite-cycled 1 H FID MRSI at ultra-high fields. An increase in Cre/NAA was seen for the metabolite-cycled case. The same methodology was further applied at 3T and similar results were observed. Magn Reson Med 80:442-451, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society

  8. Comparison of the accuracy rates of 3-T and 1.5-T MRI of the knee in the diagnosis of meniscal tear.

    PubMed

    Grossman, Jeffrey W; De Smet, Arthur A; Shinki, Kazuhiko

    2009-08-01

    The purpose of this study was to compare the accuracy of 3-T MRI with that of 1.5-T MRI of the knee in the diagnosis of meniscal tear and to analyze the causes of diagnostic error. We reviewed the medical records and original MRI interpretations of 100 consecutive patients who underwent 3-T MRI of the knee and of 100 consecutive patients who underwent 1.5-T MRI of the knee to determine the accuracy of diagnoses of meniscal tear. Knee arthroscopy was the reference standard. We retrospectively reviewed all MRI diagnostic errors to determine the cause of the errors. At arthroscopy, 109 medial and 77 lateral meniscal tears were identified in the 200 patients. With two abnormal MR images indicating a meniscal tear, the sensitivity and specificity for medial tear were 92.7% and 82.2% at 1.5-T MRI and 92.6% and 76.1% at 3-T MRI (p = 1.0, p = 0.61). The sensitivity and specificity for lateral tears were 68.4% and 95.2% at 1.5-T MRI and 69.2% and 91.8% at 3-T MRI (p = 1.0, p = 0.49). Of the false-positive diagnoses of medial meniscal tear, five of eight at 1.5 T and seven of 11 at 3 T were apparent peripheral longitudinal tears of the posterior horn. Fifteen of the 26 missed medial and lateral meniscal tears were not seen in retrospect even with knowledge of the tear type and location. Allowing for sample size limitations, we found comparable accuracy of 3-T and 1.5-T MRI of the knee in the diagnosis of meniscal tear. The causes of false-positive and false-negative MRI diagnoses of meniscal tear are similar for 3-T and 1.5-T MRI.

  9. 3D T2-weighted imaging to shorten multiparametric prostate MRI protocols.

    PubMed

    Polanec, Stephan H; Lazar, Mathias; Wengert, Georg J; Bickel, Hubert; Spick, Claudio; Susani, Martin; Shariat, Shahrokh; Clauser, Paola; Baltzer, Pascal A T

    2018-04-01

    To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. • 3D shows equivalent image quality and lesion delineation compared to 2D T2w. • 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. • Using a single 3D T2w acquisition may shorten the protocol by 40%. • Combined with short DCE, multiparametric protocols of 10 min are feasible.

  10. Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

    PubMed

    Ishikawa, Tetsuhiro; Watanabe, Atsuya; Kamoda, Hiroto; Miyagi, Masayuki; Inoue, Gen; Takahashi, Kazuhisa; Ohtori, Seiji

    2018-04-01

    An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs ( p <0.05). There was a significant difference between grade 1 and grade 2 IVDs only in terms of T1ρ values ( p <0.05). T1ρ and T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

  11. Comparison of FSE T2 W PROPELLER and 3D-FIESTA of 3 T MR for the internal auditory canal.

    PubMed

    Wu, Hai-Bo; Yuan, Hui-Shu; Ma, Furong; Zhao, Qiang

    The study compared the use of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique fast spin echo (FSE) T2 W and the sequence of three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA) technique in the MRI of the internal auditory canal for overall image quality improvement. One hundred thirty-two patients undergoing FSE T2 W PROPELLER and 3D-FIESTA examinations of the internal auditory canal were included. All examinations were performed at 3.0 T with comparison of a sagittal oblique FSE T2 W sequence with the PROPELLER technique to 3D-FIESTA in the same reconstructed orientation with PROPELLER. Image quality was evaluated by two radiologists using a 4-point scale. The Wilcoxon signed rank test was used to compare the data of the two techniques. The image quality of FSE T2 W PROPELLER was significantly improved compared to the reconstructed images of 3D-FIESTA. Observer 1: median FSE T2 W with PROPELLER, 4 [mean, 3.455] versus median reconstructed 3D-FIESTA, 3 [mean, 3.15], (P<.001); Observer 2: median FSE T2 W with PROPELLER, 4 [mean, 3.47] versus median reconstructed 3D-FIESTA, 3 [mean, 3.25], (P<.001). Interobserver agreement was good (k value, 0.73) for the rating of the overall image quality. The FSE T2 W PROPELLER technique for MRI of internal auditory canal reduced uncertainty caused by motion artifact and improved the quality of the image compared to the reconstructed 3D-FIESTA. It was affected by different parameters including the blade width, echo train length (ETL). This is explained by data oversampling at the center region of k-space, which requires additional imaging time over conventional MRI techniques. Increasing blade was expected to improve motion correction effects but also the signal-to-noise ratio. ETL increases the image sharpness and the overall image quality. Copyright © 2016. Published by Elsevier Inc.

  12. T1 and T2 Mapping in Cardiology: "Mapping the Obscure Object of Desire".

    PubMed

    Mavrogeni, Sophie; Apostolou, Dimitris; Argyriou, Panayiotis; Velitsista, Stella; Papa, Lilika; Efentakis, Stelios; Vernardos, Evangelos; Kanoupaki, Mikela; Kanoupakis, George; Manginas, Athanassios

    The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing. © 2017 S. Karger AG, Basel.

  13. Quantitative evaluation of knee cartilage and meniscus destruction in patients with rheumatoid arthritis using T1ρ and T2 mapping.

    PubMed

    Meng, Xiang Hong; Wang, Zhi; Guo, Li; Liu, Xiu Chan; Zhang, Yu Wei; Zhang, Ze Wei; Ma, Xin Long

    2017-11-01

    To calculate T1ρ and T2 values of articular cartilage and menisci in knee joints of patients with RA, and compare the values between RA patients and healthy volunteers, to gain insight into the pathogenesis of cartilage and meniscus degradation in patients with RA. Nine patients with RA and knee joints symptoms were enrolled in the study, twenty healthy volunteers without knee joint diseases were included as controls. Sagittal fat-saturated T1ρ and T2 mapping images were obtained on a 3T MR scanner (GE750, GE Healthcare, Waukesha, WI), using a dedicated 8-channel knee coil. In the T1rho mapping sequence, the amplitude of the spin-lock pulse was 500Hz, spin lock durations=10/20/30/50ms. In the T2 mapping sequence,TR/TE were 1794/6.5, 13.4, 27, 40.7ms. Both sequences were performed with the following parameters: flip angle (FA)=90°, matrix: 320×256, FOV: 16×16cm 2 , slice thickness: 3mm, bandwidth: 62.5kHZ, and a total scan time of 5:11min. T1ρ- and T2-mapping images were used for the segmentation of the articular cartilage of the patella, femoral trochlea, medial and lateral femoral condyle, medial and lateral tibial plateau. These images were also used for the segmentation of the anterior and posterior horns of the medial and lateral menisci with livewire semi-automatic segmentation algorithm of MATLAB. A Mann-Whitney U test was performed to compare the T1ρ and T2 values of the above mentioned regions between the two groups. T1ρ (Z=-3.913 to -2.121, P=0.000-0.034) and T2 (Z=-3.866 to -2.216, P=0.000-0.026) values of knee cartilage in patients with RA were higher than that in healthy volunteers, except the cartilage of the patella (T1ρ: Z=-1.273, P=0.203,T2: Z=-0.236, P=0.814) and lateral tibial plateau (T1ρ:Z=-1.037, P=0.317). The T1ρ (Z=-1.462 to 0.572, P=0.095-0.908) and T2 (Z=-1.461 to 0.278, P=0.153-0.764) values of medial and lateral menisci showed no difference between the two groups. Patients with RA exhibit diffuse knee cartilage destruction in

  14. Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

    PubMed

    Nguyen, Dang Khoa; Rochette, Emilie; Leroux, Jean-Maxime; Beaudoin, Gilles; Cossette, Patrick; Lassonde, Maryse; Guilbert, François

    2010-10-01

    High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.5 T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI. We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0 T MR study after a negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist. Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery. The frequency of detection of a new lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  15. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells

    PubMed Central

    Spolski, Rosanne; Robertson, Avril A. B.; Klos, Andreas; Rheinheimer, Claudia; Dutow, Pavel; Woodruff, Trent M.; Yu, Zu Xi; O'Neill, Luke A.; Coll, Rebecca C.; Sher, Alan; Leonard, Warren J.; Köhl, Jörg; Monk, Pete; Cooper, Matthew A.; Arno, Matthew; Afzali, Behdad; Lachmann, Helen J.; Cope, Andrew P.; Mayer-Barber, Katrin D.; Kemper, Claudia

    2016-01-01

    The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4+ T cells and initiates caspase-1–dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is an integral component of normal adaptive TH1 responses. PMID:27313051

  16. Au Nanocage Functionalized with Ultra-small Fe3O4 Nanoparticles for Targeting T1-T2Dual MRI and CT Imaging of Tumor

    NASA Astrophysics Data System (ADS)

    Wang, Guannan; Gao, Wei; Zhang, Xuanjun; Mei, Xifan

    2016-06-01

    Diagnostic approaches based on multimodal imaging of clinical noninvasive imaging (eg. MRI/CT scanner) are highly developed in recent years for accurate selection of the therapeutic regimens in critical diseases. Therefore, it is highly demanded in the development of appropriate all-in-one multimodal contrast agents (MCAs) for the MRI/CT multimodal imaging. Here a novel ideal MCAs (F-AuNC@Fe3O4) were engineered by assemble Au nanocages (Au NC) and ultra-small iron oxide nanoparticles (Fe3O4) for simultaneous T1-T2dual MRI and CT contrast imaging. In this system, the Au nanocages offer facile thiol modification and strong X-ray attenuation property for CT imaging. The ultra-small Fe3O4 nanoparticles, as excellent contrast agent, is able to provide great enhanced signal of T1- and T2-weighted MRI (r1 = 6.263 mM-1 s-1, r2 = 28.117 mM-1 s-1) due to their ultra-refined size. After functionalization, the present MCAs nanoparticles exhibited small average size, low aggregation and excellent biocompatible. In vitro and In vivo studies revealed that the MCAs show long-term circulation time, renal clearance properties and outstanding capability of selective accumulation in tumor tissues for simultaneous CT imaging and T1- and T2-weighted MRI. Taken together, these results show that as-prepared MCAs are excellent candidates as MRI/CT multimodal imaging contrast agents.

  17. CD4+ CD25high Foxp3+ regulatory T cells downregulate human Vδ2+ T-lymphocyte function triggered by anti-CD3 or phosphoantigen

    PubMed Central

    Mahan, C Scott; Thomas, Jeremy J; Boom, W Henry; Rojas, Roxana E

    2009-01-01

    2+ T cells, the major circulating T-cell receptor-γδ-positive (TCR-γδ+) T-cell subset in healthy adults, are involved in immunity against many microbial pathogens including Mycobacterium tuberculosis. Vδ2+ T cells recognize small phosphorylated metabolites (phosphoantigens), expand in response to whole M. tuberculosis bacilli, and complement the protective functions of CD4+ T cells. CD4+ CD25high Foxp3+ T cells (Tregs) comprise 5–10% of circulating T cells and are increased in patients with active tuberculosis (TB). We investigated whether, in addition to their known role in suppressing TCR-αβ+ lymphocytes, Tregs suppress Vδ2+ T-cell function. We found that depletion of Tregs from peripheral blood mononuclear cells increased Vδ2+ T-cell expansion in response to M. tuberculosis (H37Ra) in tuberculin-skin-test-positive donors. We developed a suppression assay with fluorescence-activated cell sorting-purified Tregs and Vδ2+ T cells by coincubating the two cell types at a 1 : 1 ratio. The Tregs partially suppressed interferon-γ secretion by Vδ2+ T cells in response to anti-CD3 monoclonal antibody plus interleukin-2 (IL-2). In addition, Tregs downregulated the Vδ2+ T-cell interferon-γ responses induced by phosphoantigen (BrHPP) and IL-2. Under the latter conditions there was no TCR stimulus for Tregs and therefore IL-2 probably triggered suppressor activity. Addition of purified protein derivative (PPD) increased the suppression of Vδ2+ T cells, suggesting that PPD activated antigen-specific Tregs. Our study provides evidence that Tregs suppress both anti-CD3 and antigen-driven Vδ2+ T-cell activation. Antigen-specific Tregs may therefore contribute to the Vδ2+ T-cell functional deficiencies observed in TB. PMID:19019089

  18. Foetal blood flow measured using phase contrast cardiovascular magnetic resonance--preliminary data comparing 1.5 T with 3.0 T.

    PubMed

    Tsai-Goodman, Beverly; Zhu, Meng Yuan; Al-Rujaib, Mashael; Seed, Mike; Macgowan, Christopher K

    2015-04-18

    Phase contrast cardiovascular magnetic resonance (PC CMR) has emerged as a clinical tool for blood flow quantification but its use in the foetus has been hampered by the need for gating with the foetal heart beat. The previously described metric optimized gating (MOG) technique has been successfully used to measure foetal blood flow in late gestation foetuses on a 1.5 T CMR magnet. However, there is increasing interest in performing foetal cardiac imaging using 3.0 T CMR. We describe our pilot investigation of foetal blood flow measured using 3.0 T CMR. Foetal blood flows were quantified in 5 subjects at late gestational age (35-38 weeks). Three were normal pregnancies and two were pregnancies with ventricular size discrepancy. Data were obtained at 1.5 T and 3.0 T using a previously described PC CMR protocol. After reconstruction using MOG, blood flow was quantified independently by two observers. Intra- and inter-observer reproducibility of flow measurements at the two field strengths was assessed by Pearson correlation coefficient (R(2)), linear regression and Bland Altman analysis. PC CMR flow measurements were obtained in 36 of 40 target vessels. Strong intra-observer agreement was obtained between measurements at each field strength (R(2) = 0.78, slope = 0.83 ± 0.11), with a mean bias of -1 ml/min/kg and 95% confidence limits of ±71 ml/min/kg. Inter-observer agreement was similarly high for measurements at both 1.5 T (R(2) = 0.86, slope = 0.95 ± 0.13, bias = 6 ± 52 ml/min/kg) and 3.0 T (R(2) = 0.88, slope = 0.94 ± 0.13, bias = 4 ± 47 ml/min/kg). Across all PC CMR measurements, SNR per pixel was expectedly higher at 3.0 T relative to 1.5 T (165 ± 50%). The relative differences in flow measurements between observers were low (range: 4-16%) except for pulmonary blood flow which showed much higher variability at 1.5 T (34%) versus that at 3.0 T (11%). This was attributed to the poorly

  19. Repeatability of magnetic resonance fingerprinting T1 and T2 estimates assessed using the ISMRM/NIST MRI system phantom.

    PubMed

    Jiang, Yun; Ma, Dan; Keenan, Kathryn E; Stupic, Karl F; Gulani, Vikas; Griswold, Mark A

    2017-10-01

    The purpose of this study was to evaluate accuracy and repeatability of T 1 and T 2 estimates of a MR fingerprinting (MRF) method using the ISMRM/NIST MRI system phantom. The ISMRM/NIST MRI system phantom contains multiple compartments with standardized T 1 , T 2 , and proton density values. Conventional inversion-recovery spin echo and spin echo methods were used to characterize the T 1 and T 2 values in the phantom. The phantom was scanned using the MRF-FISP method over 34 consecutive days. The mean T 1 and T 2 values were compared with the values from the spin echo methods. The repeatability was characterized as the coefficient of variation of the measurements over 34 days. T 1 and T 2 values from MRF-FISP over 34 days showed a strong linear correlation with the measurements from the spin echo methods (R 2  = 0.999 for T 1 ; R 2  = 0.996 for T 2 ). The MRF estimates over the wide ranges of T 1 and T 2 values have less than 5% variation, except for the shortest T 2 relaxation times where the method still maintains less than 8% variation. MRF measurements of T 1 and T 2 are highly repeatable over time and across wide ranges of T 1 and T 2 values. Magn Reson Med 78:1452-1457, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  20. Engineered contrast agents in a single structure for T1-T2 dual magnetic resonance imaging.

    PubMed

    Cabrera-García, Alejandro; Checa-Chavarria, Elisa; Pacheco-Torres, Jesús; Bernabeu-Sanz, Ángela; Vidal-Moya, Alejandro; Rivero-Buceta, Eva; Sastre, Germán; Fernández, Eduardo; Botella, Pablo

    2018-04-05

    The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

  1. Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

    PubMed

    Turan, Turgay; Efiloğlu, Özgür; Günaydin, Bilal; Özkanli, Şeyma; Nikerel, Emrah; Atiş, Gökhan; Çaşkurlu, Turhan; Yildirim, Asif

    2018-01-01

    To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy. Copyright® by the International Brazilian Journal of Urology.

  2. High phase-purity 1T'-MoS2- and 1T'-MoSe2-layered crystals

    NASA Astrophysics Data System (ADS)

    Yu, Yifu; Nam, Gwang-Hyeon; He, Qiyuan; Wu, Xue-Jun; Zhang, Kang; Yang, Zhenzhong; Chen, Junze; Ma, Qinglang; Zhao, Meiting; Liu, Zhengqing; Ran, Fei-Rong; Wang, Xingzhi; Li, Hai; Huang, Xiao; Li, Bing; Xiong, Qihua; Zhang, Qing; Liu, Zheng; Gu, Lin; Du, Yonghua; Huang, Wei; Zhang, Hua

    2018-06-01

    Phase control plays an important role in the precise synthesis of inorganic materials, as the phase structure has a profound influence on properties such as conductivity and chemical stability. Phase-controlled preparation has been challenging for the metallic-phase group-VI transition metal dichalcogenides (the transition metals are Mo and W, and the chalcogens are S, Se and Te), which show better performance in electrocatalysis than their semiconducting counterparts. Here, we report the large-scale preparation of micrometre-sized metallic-phase 1T'-MoX2 (X = S, Se)-layered bulk crystals in high purity. We reveal that 1T'-MoS2 crystals feature a distorted octahedral coordination structure and are convertible to 2H-MoS2 following thermal annealing or laser irradiation. Electrochemical measurements show that the basal plane of 1T'-MoS2 is much more active than that of 2H-MoS2 for the electrocatalytic hydrogen evolution reaction in an acidic medium.

  3. The Absence of Interleukin 1 Receptor–Related T1/St2 Does Not Affect T Helper Cell Type 2 Development and Its Effector Function

    PubMed Central

    Hoshino, Katsuaki; Kashiwamura, Shin-ichiro; Kuribayashi, Kozo; Kodama, Taku; Tsujimura, Tohru; Nakanishi, Kenji; Matsuyama, Tomohiro; Takeda, Kiyoshi; Akira, Shizuo

    1999-01-01

    T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2−/−) mice and examined the roles of T1/ST2. Naive CD4+ T cells isolated from T1/ST2−/− mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2−/− mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow–derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells. PMID:10562328

  4. Pancreatic Duct in Autoimmune Pancreatitis: Intraindividual Comparison of Magnetic Resonance Pancreatography at 1.5 T and 3.0 T.

    PubMed

    Kim, Jin Hee; Byun, Jae Ho; Kim, Myung-Hwan; Lee, Sung Koo; Kim, Song Cheol; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2017-08-01

    The aim of this study was to intraindividually compare magnetic resonance pancreatography (MRP) image quality at 1.5 T and 3.0 T when demonstrating main pancreatic duct (MPD) abnormalities in patients with autoimmune pancreatitis (AIP). Thirty prospectively enrolled patients with AIP underwent MRP at both 1.5 T and 3.0 T followed by endoscopic retrograde pancreatography before treatment. Two readers independently analyzed the MRP images and graded the visualization of MPD strictures and full-length MPD, using endoscopic retrograde pancreatography as the reference standard, as well as overall image artifacts on a 4-point scale. The contrast between the MPD and periductal area was calculated using a region-of-interest measurement. Visualization scores of MPD strictures and full-length MPD, and summed scores of each qualitative analysis, were significantly greater at 3.0-T MRP than at 1.5-T MRP for both readers (P ≤ 0.02). There were less image artifacts at 3.0 T compared with 1.5 T (P ≤ 0.052). The contrast between the MPD and periductal area was significantly greater at 3.0-T MRP than at 1.5-T MRP (P < 0.001). The MRP at 3.0 T was superior to 1.5-T MRP for demonstrating MPD abnormalities in AIP, with better image contrast and fewer image artifacts. Consequently, 3.0-T MRP may be useful for the diagnosis and management of patients with AIP.

  5. T1 vs. T2 weighted magnetic resonance imaging to assess total kidney volume in patients with autosomal dominant polycystic kidney disease.

    PubMed

    van Gastel, Maatje D A; Messchendorp, A Lianne; Kappert, Peter; Kaatee, Merel A; de Jong, Marissa; Renken, Remco J; Ter Horst, Gert J; Mahesh, Shekar V K; Gansevoort, Ron T

    2018-05-01

    In ADPKD patients total kidney volume (TKV) measurement using MRI is performed to predict rate of disease progression. Historically T1 weighted images (T1) were used, but the methodology of T2 weighted imaging (T2) has evolved. We compared the performance of both sequences. 40 ADPKD patients underwent an abdominal MRI at baseline and follow-up. TKV was measured by manual tracing with Analyze Direct 11.0 software. Three readers established intra- and interreader coefficients of variation (CV). T1 and T2 measured kidney volumes and growth rates were compared with ICC and Bland-Altman analyses. Participants were 49.7 ± 7.0 years of age, 55.0% female, with estimated GFR of 50.1 ± 11.5 mL/min/1.73 m 2 . CVs were low and comparable for T2 and T1 (intrareader: 0.83% [0.48-1.79] vs. 1.15% [0.34-1.77], P = 0.9, interreader: 2.18% [1.59-2.61] vs. 1.69% [1.07-3.87], P = 0.9). TKV was clinically similar, but statistically significantly different between T2 and T1: 1867 [1172-2721] vs. 1932 [1180-2551] mL, respectively (P = 0.006), with a bias of only 0.8% and high agreement (ICC 0.997). Percentage kidney growth during 2.2 ± 0.3 years was similar for T2 and T1 (9.3 ± 10.6% vs. 7.8 ± 9.9%, P = 0.1, respectively), with a bias of 1.5% and high agreement (ICC 0.843). T2 was more often of sufficient quality for volume measurement (86.7% vs. 71.1%, P < 0.001). In patients with ADPKD, measurement of kidney volume and growth rate performs similarly when using T2 compared to T1 weighted images, although T2 performs better on secondary outcome parameters; they are more often of sufficient quality for volume measurement and result in slightly lower intra- and interreader variability.

  6. The attentional blink is not affected by backward masking of T2, T2-mask SOA, or level of T2 impoverishment.

    PubMed

    Jannati, Ali; Spalek, Thomas M; Lagroix, Hayley E P; Di Lollo, Vincent

    2012-02-01

    Identification of the second of two targets (T2) is impaired when presented shortly after the first (T1). This attentional blink (AB) is thought to arise from a delay in T2 processing during which T2 is vulnerable to masking. Conventional studies have measured T2 accuracy which is constrained by the 100% ceiling. We avoided this problem by using a dynamic threshold-tracking procedure that is inherently free from ceiling constraints. In two experiments we examined how AB magnitude is affected by three masking-related factors: (a) presence/absence of T2 mask, (b) T2-mask stimulus onset asynchrony (SOA), and (c) level of T2 impoverishment (signal-to-noise ratio [SNR]). In Experiment 1, overall accuracy decreased with T2-mask SOA. The magnitude of the AB, however, was invariant with SOA and with mask presence/absence. Experiment 2 further showed that the AB was invariant with T2 SNR. The relationship among mask presence/absence, SOA, and T2 SNR and the AB is encompassed in a qualitative model.

  7. Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

    PubMed

    Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Chen, Bailiang; De Verbizier, Jacques; Beaumont, Marine; Badr, Sammy; Cotten, Anne; Blum, Alain

    2017-12-01

    To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

  8. Bet v 1-specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1-specific T-cell effector function in an activation-dependent manner.

    PubMed

    Schmetterer, Klaus G; Haiderer, Daniela; Leb-Reichl, Victoria M; Neunkirchner, Alina; Jahn-Schmid, Beatrice; Küng, Hans J; Schuch, Karina; Steinberger, Peter; Bohle, Barbara; Pickl, Winfried F

    2011-01-01

    Regulatory T (Treg) cells establish and maintain tolerance to self-antigens and many foreign antigens, such as allergens, by suppressing effector T-cell proliferation and function. We have previously shown that human T-cell receptor (TCR) αβ-chains specific for allergen-derived epitopes confer allergen specificity on peripheral blood T cells of individuals with and without allergy. To study the feasibility of generating allergen-specific human Treg cells by retroviral transduction of a transcription unit encoding forkhead box protein 3 (FOXP3) and allergen-specific TCR αβ-chains. cDNAs encoding the α and β-chains of a Bet v 1(142-153)-specific TCR (TCR alpha variable region 6/TCR beta variable region 20) and human FOXP3 were linked via picornaviral 2A sequences and expressed as single translational unit from an internal ribosomal entry site-green fluorescence protein-containing retroviral vector. Retrovirally transduced peripheral blood T cells were tested for expression of transgenes, Treg phenotype, and regulatory capacity toward allergen-specific effector T cells. Transduced T cells displayed a Treg phenotype with clear-cut upregulation of CD25, CD39, and cytotoxic T-lymphocyte antigen 4. The transduced cells were hyporesponsive in cytokine production and secretion and, like naturally occurring Treg cells, did not proliferate after antigen-specific or antigen-mimetic stimulation. However, proliferation was inducible upon exposure to exogenous IL-2. In coculture experiments, TRAV6(+)TRBV20(+)FOXP3(+) transgenic T cells, unlike FOXP3(+) single transgenic T cells or naturally occurring Treg cells, highly significantly suppressed T cell cytokine production and proliferation of corresponding allergen-specific effector T cells in an allergen-specific, dose-dependent manner. We demonstrate a transgenic approach to engineer human allergen-specific Treg cells that exert their regulatory function in an activation-dependent manner. Customized Treg cells might become

  9. Diagnostic Quality of 3D T2-SPACE Compared with T2-FSE in the Evaluation of Cervical Spine MRI Anatomy.

    PubMed

    Chokshi, F H; Sadigh, G; Carpenter, W; Allen, J W

    2017-04-01

    Spinal anatomy has been variably investigated using 3D MRI. We aimed to compare the diagnostic quality of T2 sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with T2-FSE sequences for visualization of cervical spine anatomy. We predicted that T2-SPACE will be equivalent or superior to T2-FSE for visibility of anatomic structures. Adult patients undergoing cervical spine MR imaging with both T2-SPACE and T2-FSE sequences for radiculopathy or myelopathy between September 2014 and February 2015 were included. Two blinded subspecialty-trained radiologists independently assessed the visibility of 12 anatomic structures by using a 5-point scale and assessed CSF pulsation artifact by using a 4-point scale. Sagittal images and 6 axial levels from C2-T1 on T2-FSE were reviewed; 2 weeks later and after randomization, T2-SPACE was evaluated. Diagnostic quality for each structure and CSF pulsation artifact visibility on both sequences were compared by using a paired t test. Interobserver agreement was calculated (κ). Forty-five patients were included (mean age, 57 years; 40% male). The average visibility scores for intervertebral disc signal, neural foramina, ligamentum flavum, ventral rootlets, and dorsal rootlets were higher for T2-SPACE compared with T2-FSE for both reviewers ( P < .001). Average scores for remaining structures were either not statistically different or the superiority of one sequence was discordant between reviewers. T2-SPACE showed less degree of CSF flow artifact ( P < .001). Interobserver variability ranged between -0.02-0.20 for T2-SPACE and -0.02-0.30 for T2-FSE (slight to fair agreement). T2-SPACE may be equivalent or superior to T2-FSE for the evaluation of cervical spine anatomic structures, and T2-SPACE shows a lower degree of CSF pulsation artifact. © 2017 by American Journal of Neuroradiology.

  10. IVIM diffusion-weighted imaging of the liver at 3.0 T: Comparison with 1.5 T

    PubMed Central

    Cui, Yong; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Taouli, Bachir

    2015-01-01

    Purpose To compare intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver between 1.5 T and 3.0 T in terms of parameter quantification and inter-platform reproducibility. Materials and methods In this IRB approved prospective study, 19 subjects (17 patients with chronic liver disease and 2 healthy volunteers) underwent two repeat scans at 1.5 T and 3.0 T. Each scan included IVIM DWI using 16 b values from 0 to 800 s/mm2. A single observer measured IVIM parameters for each platform and estimated signal to noise ratio (eSNR) at b0, 200, 400 and 800 s/mm2. Wilcoxon paired tests were used to compare liver eSNR and IVIM parameters. Inter-platform reproducibility was assessed by calculating within-subject coefficient of variation (CV) and Bland–Altman limits of agreement. An ice water phantom was used to test ADC variability between the two MRI systems. Results The mean invitro difference in ADC between the two platforms was 6.8%. eSNR was significantly higher at 3.0T for all selected b values (p = 0.006–0.020), except for b0 (p = 0.239). Liver IVIM parameters were significantly different between 1.5 T and 3.0 T (p = 0.005–0.044), except for ADC (p = 0.748). The inter-platform reproducibility of true diffusion coefficient (D) and ADC were good, with mean CV of 10.9% and 11.1%, respectively. Perfusion fraction (PF) and pseudodiffusion coefficient (D*) showed more limited inter-platform reproducibility (mean CV of 22.6% for PF and 46.9% for D*). Conclusion Liver D and ADC values showed good reproducibility between 1.5 T and 3.0 T platforms; while there was more variability in PF, and large variability in D* parameters between the two platforms. These findings may have implications for drug trials assessing the role of IVIM DWI in tumor response and liver fibrosis. PMID:26393236

  11. Comparison of 7T and 3T MRI in patients with moyamoya disease.

    PubMed

    Oh, Byeong Ho; Moon, Hyeong Cheol; Baek, Hyeon Man; Lee, Youn Joo; Kim, Sang Woo; Jeon, Young Jai; Lee, Gun Seok; Kim, Hong Rae; Choi, Jai Ho; Min, Kyung Soo; Lee, Mou Seop; Kim, Young Gyu; Kim, Dong Ho; Kim, Won Seop; Park, Young Seok

    2017-04-01

    Magnetic resonance imaging and magnetic resonance angiography (MRI/MRA) are widely used for evaluating the moyamoya disease (MMD). This study compared the diagnostic accuracy of 7Tesla (T) and 3T MRI/MRA in MMD. In this case control study, 12 patients [median age: 34years; range (10-66years)] with MMD and 12 healthy controls [median age: 25years; range (22-59years)] underwent both 7T and 3T MRI/MRA. To evaluate the accuracy of MRI/MRA in MMD, five criteria were compared between imaging systems of 7T and 3T: Suzuki grading system, internal carotid artery (ICA) diameter, ivy sign, flow void of the basal ganglia on T2-weighted images, and high signal intensity areas of the basal ganglia on time-of-flight (TOF) source images. No difference was observed between 7T and 3T MRI/MRA in Suzuki stage, ICA diameter, and ivy sign score; while, 7T MRI/MRA showed a higher detection rate in the flow void on T2-weighted images and TOF source images (p<0.001). Receiver operating characteristic curves of both T2 and TOF criteria showed that 7T MRI/MRA had higher sensitivity and specificity than 3T MRI/MRA. Our findings indicate that 7T MRI/MRA is superior to 3T MRI/MRA for the diagnosis of MMD in point of detecting the flow void in basal ganglia by T2-weighted and TOF images. Copyright © 2016. Published by Elsevier Inc.

  12. Reconstruction of 7T-Like Images From 3T MRI

    PubMed Central

    Bahrami, Khosro; Shi, Feng; Zong, Xiaopeng; Shin, Hae Won; An, Hongyu

    2016-01-01

    In the recent MRI scanning, ultra-high-field (7T) MR imaging provides higher resolution and better tissue contrast compared to routine 3T MRI, which may help in more accurate and early brain diseases diagnosis. However, currently, 7T MRI scanners are more expensive and less available at clinical and research centers. These motivate us to propose a method for the reconstruction of images close to the quality of 7T MRI, called 7T-like images, from 3T MRI, to improve the quality in terms of resolution and contrast. By doing so, the post-processing tasks, such as tissue segmentation, can be done more accurately and brain tissues details can be seen with higher resolution and contrast. To do this, we have acquired a unique dataset which includes paired 3T and 7T images scanned from same subjects, and then propose a hierarchical reconstruction based on group sparsity in a novel multi-level Canonical Correlation Analysis (CCA) space, to improve the quality of 3T MR image to be 7T-like MRI. First, overlapping patches are extracted from the input 3T MR image. Then, by extracting the most similar patches from all the aligned 3T and 7T images in the training set, the paired 3T and 7T dictionaries are constructed for each patch. It is worth noting that, for the training, we use pairs of 3T and 7T MR images from each training subject. Then, we propose multi-level CCA to map the paired 3T and 7T patch sets to a common space to increase their correlations. In such space, each input 3T MRI patch is sparsely represented by the 3T dictionary and then the obtained sparse coefficients are used together with the corresponding 7T dictionary to reconstruct the 7T-like patch. Also, to have the structural consistency between adjacent patches, the group sparsity is employed. This reconstruction is performed with changing patch sizes in a hierarchical framework. Experiments have been done using 13 subjects with both 3T and 7T MR images. The results show that our method outperforms previous

  13. Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

    DOE PAGES

    Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; ...

    2015-02-05

    The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

  14. T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles.

    PubMed

    Xiao, Ning; Gu, Wei; Wang, Hao; Deng, Yunlong; Shi, Xin; Ye, Ling

    2014-03-01

    To overcome the negative contrast limitations of iron oxide-based contrast agents and to improve the biocompatibility of Gd-chelate contrast agents, PEGylated Gd-doped iron oxide (PEG-GdIO) NPs as a T1-T2 dual-modal contrast agent were synthesized by the polyol method. The transverse relaxivity (r2) and longitudinal relaxivity (r1) of PEG-GdIO were determined to be 66.9 and 65.9 mM(-1) s(-1), respectively. The high r1 value and low r2/r1 ratio make PEG-GdIO NPs suitable as a T1-T2 dual-modal contrast agent. The in vivo MRI demonstrated a brighter contrast enhancement in T1-weighted image and a simultaneous darken effect in T2-weighted MR image compared to the pre-contrast image in the region of glioma. Furthermore, the biocompatibility of PEG-GdIO NPs was confirmed by the in vitro MTT cytotoxicity and in vivo histological analyses (H&E). Therefore, PEG-GdIO NPs hold great potential in T1-T2 dual-modal imaging for the diagnosis of brain glioma. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression.

    PubMed

    Callaerts-Vegh, Zsuzsanna; Moechars, Diederik; Van Acker, Nathalie; Daneels, Guy; Goris, Ilse; Leo, Sandra; Naert, Arne; Meert, Theo; Balschun, Detlef; D'Hooge, Rudi

    2013-05-15

    The excitatory neurotransmitter l-glutamate is transported into synaptic vesicles by vesicular glutamate transporters (VGluTs) to transmit glutamatergic signals. Changes in their expression have been linked to various brain disorders including schizophrenia, Parkinson's, and Alzheimer's disease. Deleting either the VGluT1 or VGluT2 gene leads to profound developmental and neurological complications and early death, but mice heterozygous for VGluT1 or VGluT2 are viable and thrive. Acquisition, retention and extinction of conditioned visuospatial and emotional responses were compared between VGluT1(+/-) and VGluT2(+/-) mice, and their wildtype littermates, using different water maze procedures, appetitive scheduled conditioning, and conditioned fear protocols. The distinct brain expression profiles of the VGluT1 and -2 isoforms particularly in telencephalic structures, such as neocortex, hippocampus and striatum, are reflected in very specific behavioral changes. VGluT2(+/-) mice were unimpaired in spatial learning tasks and fear extinction. Conversely, VGluT1(+/-) mice displayed spatial extinction learning deficits and markedly impaired fear extinction. These data indicate that VGluT1, but not VGluT2, plays a role in the neural processes underlying inhibitory learning. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Knee Cartilage Thickness, T1ρ and T2 Relaxation Time Are Related to Articular Cartilage Loading in Healthy Adults

    PubMed Central

    Van Rossom, Sam; Smith, Colin Robert; Zevenbergen, Lianne; Thelen, Darryl Gerard; Vanwanseele, Benedicte; Van Assche, Dieter; Jonkers, Ilse

    2017-01-01

    Cartilage is responsive to the loading imposed during cyclic routine activities. However, the local relation between cartilage in terms of thickness distribution and biochemical composition and the local contact pressure during walking has not been established. The objective of this study was to evaluate the relation between cartilage thickness, proteoglycan and collagen concentration in the knee joint and knee loading in terms of contact forces and pressure during walking. 3D gait analysis and MRI (3D-FSE, T1ρ relaxation time and T2 relaxation time sequence) of fifteen healthy subjects were acquired. Experimental gait data was processed using musculoskeletal modeling to calculate the contact forces, impulses and pressure distribution in the tibiofemoral joint. Correlates to local cartilage thickness and mean T1ρ and T2 relaxation times of the weight-bearing area of the femoral condyles were examined. Local thickness was significantly correlated with local pressure: medial thickness was correlated with medial condyle contact pressure and contact force, and lateral condyle thickness was correlated with lateral condyle contact pressure and contact force during stance. Furthermore, average T1ρ and T2 relaxation time correlated significantly with the peak contact forces and impulses. Increased T1ρ relaxation time correlated with increased shear loading, decreased T1ρ and T2 relaxation time correlated with increased compressive forces and pressures. Thicker cartilage was correlated with higher condylar loading during walking, suggesting that cartilage thickness is increased in those areas experiencing higher loading during a cyclic activity such as gait. Furthermore, the proteoglycan and collagen concentration and orientation derived from T1ρ and T2 relaxation measures were related to loading. PMID:28076431

  17. Yang-Baxter deformations of W2,4 × T1,1 and the associated T-dual models

    NASA Astrophysics Data System (ADS)

    Sakamoto, Jun-ichi; Yoshida, Kentaroh

    2017-08-01

    Recently, for principal chiral models and symmetric coset sigma models, Hoare and Tseytlin proposed an interesting conjecture that the Yang-Baxter deformations with the homogeneous classical Yang-Baxter equation are equivalent to non-abelian T-dualities with topological terms. It is significant to examine this conjecture for non-symmetric (i.e., non-integrable) cases. Such an example is the W2,4 ×T 1 , 1 background. In this note, we study Yang-Baxter deformations of type IIB string theory defined on W2,4 ×T 1 , 1 and the associated T-dual models, and show that this conjecture is valid even for this case. Our result indicates that the conjecture would be valid beyond integrability.

  18. Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

    PubMed

    Henninger, B; Kremser, C; Rauch, S; Eder, R; Zoller, H; Finkenstedt, A; Michaely, H J; Schocke, M

    2012-11-01

    To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms +  n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

  19. Synthesis and structure of the extended phosphazane ligand [(1,4-C6H4){N(μ-PN(t)Bu)2N(t)Bu}2](4).

    PubMed

    Sevilla, Raquel; Less, Robert J; García-Rodríguez, Raúl; Bond, Andrew D; Wright, Dominic S

    2016-02-07

    The reaction of the phenylene-bridged precursor (1,4-C6H4)[N(PCl2)2]2 with (t)BuNH2 in the presence of Et3N gives the new ligand precursor (1,4-C6H4)[N(μ-N(t)Bu)2(PNH(t)Bu)2]2, deprotonation of which with Bu2Mg gives the novel tetraanion [(1,4-C6H4){N(μ-N(t)Bu)2(PN(t)Bu)2}2](4-).

  20. Combination L-T3 and L-T4 therapy for hypothyroidism.

    PubMed

    Wartofsky, Leonard

    2013-10-01

    Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population. Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment. Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.

  1. 3.0 T plaque imaging.

    PubMed

    Hinton-Yates, Denise P; Cury, Ricardo C; Wald, Lawrence L; Wiggins, Graham C; Keil, Boris; Seethmaraju, Ravi; Gangadharamurthy, Dakshinamurthy; Ogilvy, Christopher S; Dai, Guangping; Houser, Stuart L; Stone, James R; Furie, Karen L

    2007-10-01

    The aim of this article is to evaluate 3.0 T magnetic resonance imaging for characterization of vessel morphology and plaque composition. Emphasis is placed on early and moderate stages of carotid atherosclerosis, where increases in signal-to-noise (SNR) and contrast-to-noise (CNR) ratios compared with 1.5 T are sought. Comparison of in vivo 3.0 T imaging to histopathology is performed for validation. Parallel acceleration methods applied with an 8-channel carotid array are investigated as well as higher field ex vivo imaging to explore even further gains. The overall endeavor is to improve prospective assessment of atherosclerosis stage and stability for reduction of atherothrombotic event risk. A total of 10 male and female subjects ranging in age from 22 to 72 years (5 healthy and 5 with cardiovascular disease) participated. Custom-built array coils were used with endogenous and exogenous multicontrast bright and black-blood protocols for 3.0 T carotid imaging. Comparisons were performed to 1.5 T, and ex vivo plaque was stained with hematoxylin and eosin for histology. Imaging (9.4 T) was also performed on intact specimens. The factor of 2 gain in signal-to-noise SNR is realized compared with 1.5 T along with improved wall-lumen and plaque component CNR. Post-contrast black-blood imaging within 5-10 minutes of gadolinium injection is optimal for detection of the necrotic lipid component. In a preliminary 18-month follow-up study, this method provided measurement of a 50% reduction in lipid content with minimal change in plaque size in a subject receiving aggressive statin therapy. Parallel imaging applied with signal averaging further improves 3.0 T black-blood vessel wall imaging. The use of 3.0 T for carotid plaque imaging has demonstrated increases in SNR and CNR compared with 1.5 T. Quantitative prospective studies of moderate and early plaques are feasible at 3.0 T. Continued improvements in coil arrays, 3-dimensional pulse sequences, and the use of novel

  2. Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T.

    PubMed

    Martin-Vaquero, Paula; da Costa, Ronaldo C; Echandi, Rita L; Sammet, Christina L; Knopp, Michael V; Sammet, Steffen

    2012-08-01

    The purpose of this study was to evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) to study the concentration of metabolites in the brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0 T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained showed that all dogs had excellent quality spectra for a small (1 cm3) and large (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable method to study metabolite concentrations in the canine brain. The development of more advanced water suppression techniques is necessary to improve the results at 7.0 T. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Incidental pT2-T3 gallbladder cancer after a cholecystectomy: outcome of staging at 3 months prior to a radical resection

    PubMed Central

    Ausania, Fabio; Tsirlis, Theodoris; White, Steven A; French, Jeremy J; Jaques, Bryon C; Charnley, Richard M; Manas, Derek M

    2013-01-01

    Introduction Patients with incidental pT2-T3 gallbladder cancer (IGC) after a cholecystectomy may benefit from a radical re-resection although their optimal treatment strategy is not well defined. In this Unit, such patients undergo delayed staging at 3 months after a cholecystectomy to assess the evidence of a residual tumour, extra hepatic spread and the biological behaviour of the tumour. The aim of this study was to evaluate the outcome of patients who had delayed staging at 3 months after a cholecystectomy. Methods From July 2003 to July 2011, 56 patients with T2-T3 gallbladder cancer were referred to this Unit of which 49 were diagnosed incidentally on histology after a cholecystectomy. All 49 patients underwent delayed pre-operative staging using multi-detector computed tomography (MDCT) followed selectively by laparoscopy at 3 months after a cholecystectomy. Data were collected from a prospectively held database. The peri-operative and long-term outcomes of patients were analysed. SPSS software was used for statistical analysis. Results There were 38 pT2 and 11 pT3 tumours. After delayed staging, 24/49 (49%) patients underwent a radical resection, 24/49 (49%) were found to be inoperable on pre-operative assessment and 1/49 (2%) patient underwent an exploratory laparotomy and were found to be unresectable. The overall median survival from referral was 20.7 months (54.8 months for the group who had a radical re-resection versus 9.7 months for the group who had unresectable disease, P < 0.001). These results compare favourably with the reported outcome of fast-track management for incidental pT2-T3 gallbladder cancer from other major series in the literature. Conclusion Delayed staging in patients with incidental T2-T3 gallbladder cancer after a cholecystectomy is a useful strategy to select patients who will benefit from a resection and avoid unnecessary major surgery. PMID:23458168

  4. The Attentional Blink Is Not Affected by Backward Masking of T2, T2-Mask SOA, or Level of T2 Impoverishment

    ERIC Educational Resources Information Center

    Jannati, Ali; Spalek, Thomas M.; Lagroix, Hayley E. P.; Di Lollo, Vincent

    2012-01-01

    Identification of the second of two targets (T2) is impaired when presented shortly after the first (T1). This "attentional blink" (AB) is thought to arise from a delay in T2 processing during which T2 is vulnerable to masking. Conventional studies have measured T2 accuracy which is constrained by the 100% ceiling. We avoided this problem by using…

  5. Isotropic morphometry and multicomponent T1 ρ mapping of human knee articular cartilage in vivo at 3T.

    PubMed

    Baboli, Rahman; Sharafi, Azadeh; Chang, Gregory; Regatte, Ravinder R

    2018-05-02

    The progressive loss of hyaline articular cartilage due to osteoarthritis (OA) changes the functional and biochemical properties of cartilage. Measuring the T 1 ρ along with the morphological assessment can potentially be used as noninvasive biomarkers in detecting early-stage OA. To correlate the biochemical and morphological data, submillimeter isotropic resolution for both studies is required. To implement a high spatial resolution 3D-isotropic-MRI sequence for simultaneous assessment of morphological and biexponential T 1 ρ relaxometry of human knee cartilage in vivo. Prospective. Ten healthy volunteers with no known inflammation, trauma, or pain in the knee. Standard FLASH sequence and customized Turbo-FLASH sequence to acquire 3D-isotropic-T 1 ρ-weighted images on a 3T MRI scanner. The mean volume and thickness along with mono- and biexponential T 1 ρ relaxations were assessed in the articular cartilage of 10 healthy volunteers. Nonparametric rank-sum tests. Bland-Altman analysis and coefficient of variation. The mean monoexponential T 1 ρ relaxation was 40.7 ± 4.8 msec, while the long and short components were 58.2 ± 3.9 msec and 6.5 ± 0.6 msec, respectively. The mean fractions of long and short T 1 ρ relaxation components were 63.7 ± 5.9% and 36.3 ± 5.9%, respectively. Statistically significant (P ≤ 0.03) differences were observed in the monoexponential and long components between some of the regions of interest (ROIs). No gender differences between biexponential components were observed (P > 0.05). Mean cartilage volume and thickness were 25.9 ± 6.4 cm 3 and 2.2 ± 0.7 mm, respectively. Cartilage volume (P = 0.01) and thickness (P = 0.03) were significantly higher in male than female participants across all ROIs. Bland-Altman analysis showed agreement between two morphological methods with limits of agreement between -1000 mm 3 and +1100 mm 3 for volume, and -0.78 mm and +0.46 mm for

  6. Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis.

    PubMed

    Di, Lie; Srivastava, Shekhar; Zhdanova, Olga; Ding, Yi; Li, Zhai; Wulff, Heike; Lafaille, Maria; Skolnik, Edward Y

    2010-01-26

    The calcium-activated K(+) channel KCa3.1 plays an important role in T lymphocyte Ca(2+) signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca(2+) influx. To assess the role of KCa3.1 channels in lymphocyte activation in vivo, we studied T cell function in KCa3.1(-/-) mice. CD4 T helper (i.e., Th0) cells isolated from KCa3.1(-/-) mice lacked KCa3.1 channel activity, which resulted in decreased T cell receptor-stimulated Ca(2+) influx and IL-2 production. Although loss of KCa3.1 did not interfere with CD4 T cell differentiation, both Ca(2+) influx and cytokine production were impaired in KCa3.1(-/-) Th1 and Th2 CD4 T cells, whereas T-regulatory and Th17 function were normal. We found that inhibition of KCa3.1(-/-) protected mice from developing severe colitis in two mouse models of inflammatory bowel disease, which were induced by (i) the adoptive transfer of mouse naïve CD4 T cells into rag2(-/-) recipients and (ii) trinitrobenzene sulfonic acid. Pharmacologic inhibitors of KCa3.1 have already been shown to be safe in humans. Thus, if these preclinical studies continue to show efficacy, it may be possible to rapidly test whether KCa3.1 inhibitors are efficacious in patients with inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.

  7. Short-term stability of T1 and T2 relaxation measures in multiple sclerosis normal appearing white matter.

    PubMed

    Liang, Alice L W; Vavasour, Irene M; Mädler, Burkhard; Traboulsee, Anthony L; Lang, Donna J; Li, David K B; MacKay, Alex L; Laule, Cornelia

    2012-06-01

    The presence of diffuse and widespread abnormalities within the 'normal appearing' white matter (NAWM) of multiple sclerosis (MS) brain has been established. T(1) histogram analysis has revealed increased T(1) (related to water content) in segmented NAWM, while quantitative assessment of T(2) relaxation measures has demonstrated decreased myelin water fraction (MWF, related to myelin content) and increased geometric mean T(2) (GMT(2)) of the intra/extracellular water pool. Previous studies with follow-up periods of 1-5 years have demonstrated longitudinal changes in T(1) histogram metrics over time; however, longitudinal changes in MWF and GMT(2) of segmented NAWM have not been examined. We examined the short-term evolution of MWF, GMT(2) and T(1) in MS NAWM based on monthly scanning over 6 months in 18 relapsing remitting (RR) MS subjects. Histogram metrics demonstrated short-term stability of T(1), MWF and remitting (RR) MS subjects. We observed no change in MWF, GMT(2) or T(1) histogram metrics in NAWM in RRMS over the course of 6 months. Longer follow-up periods may be required to establish demonstrable changes in NAWM based on of MWF, GMT(2) and T(1) metrics.

  8. Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor

    PubMed Central

    Assadi-Porter, Fariba M.; Maillet, Emeline L.; Radek, James T.; Quijada, Jeniffer; Markley, John L.; Max, Marianna

    2010-01-01

    The sweet protein brazzein activates the human sweet receptor, a heterodimeric G-protein coupled receptor (GPCR) composed of subunits T1R2 and T1R3. In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by the in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: Site 1 (Loop43), Site 2 (N- and C-terminus and adjacent Glu36, Loop33), and Site 3 (Loop9–19). Basic residues in Site 1 and acidic residues in Site 2 were essential for positive responses from each assay. Mutation of Y39A (Site 1) greatly reduced positive responses. A bulky side chain at position 54 (Site 2), rather than a side chain with hydrogen bonding potential, was required for positive responses as was the presence of the native disulfide bond in Loop 9–19 (Site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus fly trap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in the brazzein response. The exception, hT1R2:R217A-hT1R3, which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase the positive cooperativity of binding by multiple ligands proposed to bind both T1R subunits (brazzein, monellin, and sucralose) but not those that bind to a single subunit (neotame and cyclamate), we suggest that this site in involved in subunit-subunit interaction rather than direct

  9. Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial.

    PubMed

    Zeidan, Youssef H; Habib, Joyce G; Ameye, Lieveke; Paesmans, Marianne; de Azambuja, Evandro; Gelber, Richard D; Campbell, Ian; Nordenskjöld, Bo; Gutiérez, Jorge; Anderson, Michael; Lluch, Ana; Gnant, Michael; Goldhirsch, Aron; Di Leo, Angelo; Joseph, David J; Crown, John; Piccart-Gebhart, Martine; Francis, Prudence A

    2018-06-01

    To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P = .005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P = .02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Our analysis of the BIG 02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. 26 CFR 1.103(n)-3T - Private activity bond limit (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Private activity bond limit (temporary). 1.103(n)-3T Section 1.103(n)-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....103(n)-3T Private activity bond limit (temporary). Q-1: What is the “State ceiling”? A-1: In general...

  11. 26 CFR 1.103(n)-3T - Private activity bond limit (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Private activity bond limit (temporary). 1.103(n)-3T Section 1.103(n)-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....103(n)-3T Private activity bond limit (temporary). Q-1: What is the “State ceiling”? A-1: In general...

  12. The association between MR T1ρ and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction.

    PubMed

    Su, F; Pedoia, V; Teng, H-L; Kretzschmar, M; Lau, B C; McCulloch, C E; Link, T M; Ma, C B; Li, X

    2016-07-01

    To determine if cartilage T1ρ and T2 relaxation time measures after ACL injury and prior to reconstruction (baseline) are associated with patient-reported outcomes at baseline, 6-months, and 1-year after surgery. Fifty-four ACL-injured participants were scanned in both knees at baseline using 3T MR T1ρ and T2 mapping. Participants also completed Knee-injury and Osteoarthritis Outcome Score (KOOS) and Marx activity level questionnaires at baseline, 6-months, and 1-year after reconstruction. The difference between cartilage T1ρ or T2 of the injured and contralateral knee (side-to-side difference, SSD) was calculated to account for physiological variations among patients. Linear regression models were built to evaluate the association between the baseline SSD T1ρ or T2 and KOOS or Marx at all time points. Higher baseline SSD T1ρ posterolateral tibia (pLT) was associated with worse KOOS in all subscales except symptoms at baseline, worse KOOS pain at 6-months, and worse KOOS in all subscales except sports function at 1-year. Higher baseline SSD T2 femoral trochlea (TrF) was associated with worse KOOS activities of daily living (ADL) at 1-year. Higher baseline SSD T1ρ pLT was associated with lower Marx activity level at 1-year. More severe cartilage lesions, as assessed by Whole-Organ MRI Scoring (WORMS), was significantly associated with worse KOOS pain at 6-months and 1-year. T1ρ and T2 of cartilage after ACL injury were associated with KOOS after injury and both KOOS and Marx after reconstruction. Such associations may help clinicians stratify outcomes post-injury, and thus, improve patient management. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  13. Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

    PubMed Central

    Righart, Ruthger; Biberacher, Viola; Jonkman, Laura E.; Klaver, Roel; Schmidt, Paul; Buck, Dorothea; Berthele, Achim; Kirschke, Jan S.; Zimmer, Claus; Hemmer, Bernhard; Geurts, Jeroen J. G.

    2017-01-01

    Objective In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Methods Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Results Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. Interpretation The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529 PMID:28833433

  14. Hydrogels incorporating GdDOTA: towards highly efficient dual T1/T2 MRI contrast agents.

    PubMed

    Courant, Thomas; Roullin, Valérie Gaëlle; Cadiou, Cyril; Callewaert, Maïté; Andry, Marie Christine; Portefaix, Christophe; Hoeffel, Christine; de Goltstein, Marie Christine; Port, Marc; Laurent, Sophie; Elst, Luce Vander; Muller, Robert; Molinari, Michaël; Chuburu, Françoise

    2012-09-03

    Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles (GdDOTA NPs) exhibited high relaxivity (r(1) =101.7 s(-1) mM(-1) per Gd(3+) ion at 37 °C and 20 MHz). This high relaxation rate is due to efficient Gd loading, reduced tumbling of the Gd complex, and the hydrogel nature of the nanoparticles. The efficacy of the nanoparticles as a T(1)/T(2) dual-mode contrast agent was studied in C6 cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Controlling Magnetism via Transition Metal Exchange in the Series of Intermetallics Eu( T1, T2)5In ( T = Cu, Ag, Au)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mudring, Anja -Verena; Smetana, Volodymyr; Pecharsky, Vitalij K.

    Three series of intermetallic compounds Eu( T1, T2) 5In (T = Cu, Ag, Au) have been investigated in full compositional ranges. Single crystals of all compounds have been obtained by self-flux and were analyzed by single X-ray diffraction revealing the representatives to fall into two structure types: CeCu 6 ( oP28, Pnma, a = 8.832(3)–9.121(2) Å, b = 5.306(2)–5.645(1) Å, c = 11.059(4)–11.437(3) Å, V = 518.3(3)–588.9(2) Å 3) and YbMo2Al4 ( t I14, I4/ mmm, a = 5.417(3)–5.508(1) Å, c = 7.139(2)– 7.199(2) Å, V = 276.1(2)–285.8(1) Å 3). The structural preference was found to depend on the cation/anionmore » size ratio, while the positional preference within the CeCu 6 type structure shows an apparent correlation with the anion size. Chemical compression, hence, a change in cell volume, which occurs upon anion substitution appears to be the main driving force for the change of magnetic ordering. While EuAg 5In shows antiferromagnetic behavior at low temperatures, mixing Cu and Au within the same type of structure results in considerable changes in the magnetism. The Eu(Cu,Au) 5In alloys with CeCu 6 structure show complex magnetic behaviors and strong magnetic field-induced spin-reorientation transition with the critical field of the transition being dependent on Cu/Au ratio. The alloys adopting the YbMo 2Al 4 type structure are ferromagnets exhibiting unusually high magnetic moments. The heat capacity of EuAu 2.66Cu 2.34In reveals a double-peak structure evolving with the magnetic field. Furthermore, low-temperature X-ray powder diffraction does not show a structural transition.« less

  16. Controlling Magnetism via Transition Metal Exchange in the Series of Intermetallics Eu( T1, T2)5In ( T = Cu, Ag, Au)

    DOE PAGES

    Mudring, Anja -Verena; Smetana, Volodymyr; Pecharsky, Vitalij K.; ...

    2017-11-24

    Three series of intermetallic compounds Eu( T1, T2) 5In (T = Cu, Ag, Au) have been investigated in full compositional ranges. Single crystals of all compounds have been obtained by self-flux and were analyzed by single X-ray diffraction revealing the representatives to fall into two structure types: CeCu 6 ( oP28, Pnma, a = 8.832(3)–9.121(2) Å, b = 5.306(2)–5.645(1) Å, c = 11.059(4)–11.437(3) Å, V = 518.3(3)–588.9(2) Å 3) and YbMo2Al4 ( t I14, I4/ mmm, a = 5.417(3)–5.508(1) Å, c = 7.139(2)– 7.199(2) Å, V = 276.1(2)–285.8(1) Å 3). The structural preference was found to depend on the cation/anionmore » size ratio, while the positional preference within the CeCu 6 type structure shows an apparent correlation with the anion size. Chemical compression, hence, a change in cell volume, which occurs upon anion substitution appears to be the main driving force for the change of magnetic ordering. While EuAg 5In shows antiferromagnetic behavior at low temperatures, mixing Cu and Au within the same type of structure results in considerable changes in the magnetism. The Eu(Cu,Au) 5In alloys with CeCu 6 structure show complex magnetic behaviors and strong magnetic field-induced spin-reorientation transition with the critical field of the transition being dependent on Cu/Au ratio. The alloys adopting the YbMo 2Al 4 type structure are ferromagnets exhibiting unusually high magnetic moments. The heat capacity of EuAu 2.66Cu 2.34In reveals a double-peak structure evolving with the magnetic field. Furthermore, low-temperature X-ray powder diffraction does not show a structural transition.« less

  17. Magnetic resonance fingerprinting using echo-planar imaging: Joint quantification of T1 and T2∗ relaxation times.

    PubMed

    Rieger, Benedikt; Zimmer, Fabian; Zapp, Jascha; Weingärtner, Sebastian; Schad, Lothar R

    2017-11-01

    To develop an implementation of the magnetic resonance fingerprinting (MRF) paradigm for quantitative imaging using echo-planar imaging (EPI) for simultaneous assessment of T 1 and T2∗. The proposed MRF method (MRF-EPI) is based on the acquisition of 160 gradient-spoiled EPI images with rapid, parallel-imaging accelerated, Cartesian readout and a measurement time of 10 s per slice. Contrast variation is induced using an initial inversion pulse, and varying the flip angles, echo times, and repetition times throughout the sequence. Joint quantification of T 1 and T2∗ is performed using dictionary matching with integrated B1+ correction. The quantification accuracy of the method was validated in phantom scans and in vivo in 6 healthy subjects. Joint T 1 and T2∗ parameter maps acquired with MRF-EPI in phantoms are in good agreement with reference measurements, showing deviations under 5% and 4% for T 1 and T2∗, respectively. In vivo baseline images were visually free of artifacts. In vivo relaxation times are in good agreement with gold-standard techniques (deviation T 1 : 4 ± 2%, T2∗: 4 ± 5%). The visual quality was comparable to the in vivo gold standard, despite substantially shortened scan times. The proposed MRF-EPI method provides fast and accurate T 1 and T2∗ quantification. This approach offers a rapid supplement to the non-Cartesian MRF portfolio, with potentially increased usability and robustness. Magn Reson Med 78:1724-1733, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  18. Three-dimensional T1 and T2* mapping of human lung parenchyma using interleaved saturation recovery with dual echo ultrashort echo time imaging (ITSR-DUTE).

    PubMed

    Gai, Neville D; Malayeri, Ashkan A; Bluemke, David A

    2017-04-01

    To develop and assess a new technique for three-dimensional (3D) full lung T1 and T2* mapping using a single free breathing scan during a clinically feasible time. A 3D stack of dual-echo ultrashort echo time (UTE) radial acquisition interleaved with and without a WET (water suppression enhanced through T1 effects) saturation pulse was used to map T1 and T2* simultaneously in a single scan. Correction for modulation due to multiple views per segment was derived. Bloch simulations were performed to study saturation pulse excitation profile on lung tissue. Optimization of the saturation delay time (for T1 mapping) and echo time (for T2* mapping) was performed. Monte Carlo simulation was done to predict accuracy and precision of the sequence with signal-to-noise ratio of in vivo images used in the simulation. A phantom study was carried out using the 3D interleaved saturation recovery with dual echo ultrashort echo time imaging (ITSR-DUTE) sequence and reference standard inversion recovery spin echo sequence (IR-SE) to compare accuracy of the sequence. Nine healthy volunteers were imaged and mean (SD) of T1 and T2* in lung parenchyma at 3T were estimated through manually assisted segmentation. 3D lung coverage with a resolution of 2.5 × 2.5 × 6 mm 3 was performed and nominal scan time was recorded for the scans. Repeatability was assessed in three of the volunteers. Regional differences in T1/T2* values were also assessed. The phantom study showed accuracy of T1 values to be within 2.3% of values obtained from IR-SE. Mean T1 value in lung parenchyma was 1002 ± 82 ms while T2* was 0.85 ± 0.1 ms. Scan time was ∼10 min for volunteer scans. Mean coefficient of variation (CV) across slices was 0.057 and 0.09, respectively. Regional variation along the gravitational direction and between right and left lung were not significant (P = 0.25 and P = 0.06, respectively) for T1. T2* showed significant variation (P = 0.03) along the

  19. Advantages of T2 Weighted Three Dimensional and T1 Weighted Three Dimensional Contrast Medium Enhanced Magnetic Resonance Urography in Examination of the Child Population.

    PubMed

    Sehic, Adnan; Julardzija, Fuad; Vegar-Zubovic, Sandra; Sefic-Pasic, Irmina

    2017-03-01

    The aim of this study is to prove the advantages of combined use of T2 weighted three dimensional (T2 W 3D) and T1 weighted three dimensional contrast medium enhanced (T1 W 3D CE) magnetic resonance (MR) urography in displaying urinary tract in child population. Total of 120 patients were included in the study, 71 (59%) male patients and 49 (41%) female patients. The study was conducted on the Radiology clinic, University of Sarajevo Clinical Center, during the period from February to November 2016. Patients were examined on the 1.5T and 3T MRI, with standard protocol which includes T2 W 3D and T1 W 3D contrast medium enhanced MR urography. In the post procesing quantitative measurement of signal intensity and evaluation of the display quality in the area of renal pelvis, middle of ureter and the mouth of the ureter were done. Measurement was concluded on Syngo software B13. Analyzing the acquired data and statistically processing them we got results which have shown higher signal intensity of measured structures on T1 W 3D contrast medium enhanced MR urography on the level p<0.01 and p<0.05 compared to T2 W 3D MR urography in patients that had normal dynamics of contrast medium secretion. However, in kidneys with decreased function, T2 W 3D MR urography provided higher signal intensity and better display compared to T1 W 3D contrast medium enhanced MR urography on the level p<0.05 and p<0.01. T2 W3D MR urography is useful in imaging nonfunctional kidney as well as in patients prone to allergic reactions, where as T1 W3D CE MR urography is at an advantage over T2 W 3D MR urography in imaging the kidney functionality, kidney dynamics measurement, it provides higher MRI signal intensity required for clear 3D reconstructions.

  20. Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to triiodothyronine (T3) in chicken thyroids.

    PubMed

    Lin, Shi-lei; Wang, Cong-wu; Tan, Si-ran; Liang, Yang; Yao, Hai-dong; Zhang, Zi-wei; Xu, Shi-wen

    2014-12-01

    Selenium (Se) influences the metabolism of thyroid hormones in mammals. However, the role of Se deficiency in the regulation of thyroid hormones in chickens is not well known. In the present study, we examined the levels of thyroidal triiodothyronine (T3), thyroidal thyroxine (T4), free triiodothyronine, free thyroxine (FT4), and thyroid-stimulating hormone in the serum and the mRNA expression levels of 25 selenoproteins in chicken thyroids. Then, principal component analysis (PCA) was performed to analyze the relationships between the selenoproteins. The results indicated that Se deficiency influenced the conversion of T4 to T3 and induced the accumulation of T4 and FT4. In addition, the mRNA expression levels of the selenoproteins were generally decreased by Se deficiency. The PCA showed that eight selenoproteins (deiodinase 1 (Dio1), Dio2, Dio3, thioredoxin reductase 2 (Txnrd2), selenoprotein i (Seli), selenoprotein u (Selu), glutathione peroxidase 1 (Gpx1), and Gpx2) have similar trends, which indicated that they may play similar roles in the metabolism of thyroid hormones. The results showed that Se deficiency inhibited the conversion of T4 to T3 and decreased the levels of the crucial metabolic enzymes of the thyroid hormones, Dio1, Dio2, and Dio3, in chickens. In addition, the decreased selenoproteins (Dio1, Dio2, Dio3, Txnrd2, Seli, Selu, Gpx1, and Gpx2) induced by Se deficiency may indirectly limit the conversion of T4 to T3 in chicken thyroids. The information presented in this study is helpful to understand the role of Se in the thyroid function of chickens.

  1. IDEAL 3D spoiled gradient echo of the articular cartilage of the knee on 3.0 T MRI: a comparison with conventional 3.0 T fast spin-echo T2 fat saturation image.

    PubMed

    Han, Chul Hee; Park, Hee Jin; Lee, So Yeon; Chung, Eun Chul; Choi, Seon Hyeong; Yun, Ji Sup; Rho, Myung Ho

    2015-12-01

    Many two-dimensional (2D) morphologic cartilage imaging sequences have disadvantages such as long acquisition time, inadequate spatial resolution, suboptimal tissue contrast, and image degradation secondary to artifacts. IDEAL imaging can overcome these disadvantages. To compare sound-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and quality of two different methods of imaging that include IDEAL 3D SPGR and 3.0-T FSE T2 fat saturation (FS) imaging and to evaluate the utility of IDEAL 3D SPGR for knee joint imaging. SNR and CNR of the patellar and femoral cartilages were measured and calculated. Two radiologists performed subjective scoring of all images for three measures: general image quality, FS, and cartilage evaluation. SNR and CNR values were compared by paired Student's t-tests. Mean SNRs of patellar and femoral cartilages were 90% and 66% higher, respectively, for IDEAL 3D SPGR. CNRs of patellar cartilages and joint fluids were 2.4 times higher for FSE T2 FS, and CNR between the femoral cartilage and joint fluid was 2.2 times higher for FSE T2 FS. General image quality and FS were superior using FSE T2 FS compared to those of IDEAL 3D SPGR imaging according to both readers, while cartilage evaluation was superior using IDEAL 3D SPGR. Additionally, cartilage injuries were more prominent in IDEAL 3D SPGR than in FSE T2FS according to both readers. IDEAL 3D SPGR images show excellent visualization of patellar and femoral cartilages in 3.0 T and can compensate for the weaknesses of FSE T2 FS in the evaluation of cartilage injuries. © The Foundation Acta Radiologica 2014.

  2. Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

    PubMed Central

    Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

    2015-01-01

    Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. Conclusion Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis

  3. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group.

    PubMed

    Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2015-03-01

    The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ=0.737 and ρ=0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Maximizing T2-exchange in Dy3+DOTA-(amide)X chelates: Fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI

    PubMed Central

    Soesbe, Todd C.; Ratnakar, S. James; Milne, Mark; Zhang, Shanrong; Do, Quyen N.; Kovacs, Zoltan; Sherry, A. Dean

    2014-01-01

    Purpose The water molecule exchange rates in a series of DyDOTA-(amide)X chelates were fine-tuned to maximize the effects of T2-exchange line broadening and improve T2 contrast. Methods Four DyDOTA-(amide)X chelates having a variable number of glycinate side-arms were prepared and characterized as T2-exchange agents. The non-exchanging DyTETA chelate was also used to measure the bulk water T2 reduction due solely to T2*. The total transverse relaxivity (r2tot) at 22, 37, and 52 °C for each chelate was measured in vitro at 9.4 T (400 MHz) by fitting plots of total T21 versus concentration. The water molecule exchange rates for each complex were measured by fitting 17O line-width versus temperature data taken at 9.4 T (54.3 MHz). Results The measured transverse relaxivities due to water molecule exchange (r2ex) and bound water lifetimes (τM) were in excellent agreement with Swift-Connick theory, with DyDOTA-(gly)3 giving the largest r2ex = 11.8 s−1 mM−1 at 37 °C. Conclusion By fine-tuning the water molecule exchange rate at 37 °C, the transverse relaxivity has been increased by 2 to 30 times compared to previously studied Dy3+-based chelates. Polymerization or dendrimerization of the optimal chelate could yield a highly sensitive, molecule-sized T2 contrast agent for improved molecular imaging applications. PMID:24390729

  5. Does fat suppression via chemically selective saturation affect R2*-MRI for transfusional iron overload assessment? A clinical evaluation at 1.5T and 3T.

    PubMed

    Krafft, Axel J; Loeffler, Ralf B; Song, Ruitian; Bian, Xiao; McCarville, M Beth; Hankins, Jane S; Hillenbrand, Claudia M

    2016-08-01

    Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat-water oscillations in multiecho gradient echo (mGRE) R2*-MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. We investigated the effect of CHESS on R2* and developed a heuristic correction for the observed CHESS-induced R2* changes. Eighty patients [female, n = 49; male, n = 31; mean age (± standard deviation), 18.3 ± 11.7 y] with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at 1.5T and 3T. Mean liver R2* values were evaluated using three published fitting approaches. Measured and model-corrected R2* values were compared and statistically analyzed. At 1.5T, CHESS led to a systematic R2* reduction (P < 0.001 for all fitting algorithms) especially toward higher R2*. Our model described the observed changes well and reduced the CHESS-induced R2* bias after correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2* reductions were found at 3T. The CHESS-induced R2* bias at 1.5T needs to be considered when applying R2*-LIC biopsy calibrations for clinical LIC assessment, which were established without FS at 1.5T. The proposed model corrects the R2* bias and could therefore improve clinical iron overload assessment based on linear R2*-LIC calibrations. Magn Reson Med 76:591-601, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. βig-h3 Represses T-Cell Activation in Type 1 Diabetes.

    PubMed

    Patry, Maeva; Teinturier, Romain; Goehrig, Delphine; Zetu, Cornelia; Ripoche, Doriane; Kim, In-San; Bertolino, Philippe; Hennino, Ana

    2015-12-01

    βig-h3/TGF-βi is a secreted protein capable of binding to both extracellular matrix and cells. Human genetic studies recently revealed that in the tgfbi gene encoding for βig-h3, three single nucleotide polymorphisms were significantly associated with type 1 diabetes (T1D) risk. Pancreatic islets express βig-h3 in physiological conditions, but this expression is reduced in β-cell insult in T1D. Since the integrity of islets is destroyed by autoimmune T lymphocytes, we thought to investigate the impact of βig-h3 on T-cell activation. We show here that βig-h3 inhibits T-cell activation markers as well as cytotoxic molecule production as granzyme B and IFN-γ. Furthermore, βig-h3 inhibits early T-cell receptor signaling by repressing the activation of the early kinase protein Lck. Moreover, βig-h3-treated T cells are unable to induce T1D upon transfer in Rag2 knockout mice. Our study demonstrates for the first time that T-cell activation is modulated by βig-h3, an islet extracellular protein, in order to efficiently avoid autoimmune response. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Performance Comparison of 1.5 T Endorectal Coil MRI with Non-Endorectal Coil 3.0 T MRI in Patients with Prostate Cancer

    PubMed Central

    Shah, Zarine K.; Elias, Saba N.; Abaza, Ronney; Zynger, Debra L.; DeRenne, Lawrence A.; Knopp, Michael V.; Guo, Beibei; Schurr, Ryan; Heymsfield, Steven B.; Jia, Guang

    2015-01-01

    Rationale and Objectives To compare prostate morphology, image quality, and diagnostic performance of 1.5 T endorectal coil MRI and 3.0 T non-endorectal coil MRI in patients with prostate cancer. Materials and Methods MR images obtained of 83 patients with prostate cancer using 1.5 T MRI systems with an endorectal coil were compared to images collected from 83 patients with a 3.0 T MRI system. Prostate diameters were measured and image quality was evaluated by one ABR-certified radiologist (Reader 1) and one ABR-certified diagnostic medical physicist (Reader 2). The likelihood of the peripheral zone cancer presence in each sextant and local extent were rated and compared with histopathologic findings. Results Prostate anterior-posterior diameter measured by both readers was significantly shorter with 1.5 T endorectal MRI than with 3.0 T MRI. The overall image quality score difference was significant only for Reader 1. Both readers found that the two MRI systems provided similar diagnostic accuracy in cancer localization, extraprostatic extension, and seminal vesicle involvement. Conclusion Non-endorectal coil 3.0 T MRI provides prostate images that are natural in shape and that have comparable image quality to those obtained at 1.5 T with an endorectal coil, but not superior diagnostic performance. These findings suggest an opportunity exists for improving technical aspects of 3.0 T prostate MRI. PMID:25579637

  8. Quantitative Mapping of Human Cartilage at 3.0T

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Rationale and Objectives The objectives of this study were to measure the parallel changes of transverse relaxation times (T2), spin-lattice relaxation time in the rotating frame (T1ρ), and the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)-T1 mapping of human knee cartilage in detecting cartilage degeneration at 3.0T. Materials and Methods Healthy volunteers (n = 10, mean age 35.6 years) and patients (n = 10, mean age 65 years) with early knee osteoarthritis (OA) were scanned at 3.0T MR using an 8-channel phased array knee coil (transmit–receive). Quantitative assessment of T2, T1ρ, and dGEMRIC-T1 values (global and regional) were correlated between asymptomatic subjects and patients with OA. Results The average T2 (39 ± 2 milliseconds [mean ± standard deviation] vs. 47 ± 6 milliseconds, P < .0007) and T1ρ (48 ± 3 vs. 62 ± 8 milliseconds, P < .0002) values were all markedly increased in all patients with OA when compared to healthy volunteers. The average dGEMRIC-T1 (1244 ± 134 vs. 643 ± 227 milliseconds, P < .000002) value was sharply decreased after intravenous administration of gadolinium contrast agent in all patients with OA. Conclusions The research results showed that all the T2, T1ρ, and dGEMRIC-T1 relaxation times varied with the cartilage degeneration. The dGEMRIC-T1 and T1ρ relaxation times seem to be more sensitive than T2 in detecting early cartilage degeneration. The preliminary study demonstrated that the early biochemical changes in knee osteoarthritic patients could be detected noninvasively in in vivo using T1ρ and dGEMRIC-T1 mapping. PMID:24594416

  9. Temperature- and Phase-Dependent Phonon Renormalization in 1T'-MoS2.

    PubMed

    Tan, Sherman Jun Rong; Sarkar, Soumya; Zhao, Xiaoxu; Luo, Xin; Luo, Yong Zheng; Poh, Sock Mui; Abdelwahab, Ibrahim; Zhou, Wu; Venkatesan, Thirumalai; Chen, Wei; Quek, Su Ying; Loh, Kian Ping

    2018-05-22

    Polymorph engineering of 2H-MoS 2 , which can be achieved by alkali metal intercalation to obtain either the mixed 2H/1T' phases or a homogeneous 1T' phase, has received wide interest recently, since this serves as an effective route to tune the electrical and catalytic properties of MoS 2 . As opposed to an idealized single crystal-to-single crystal phase conversion, the 2H to 1T' phase conversion results in crystal domain size reduction as well as strained lattices, although how these develop with composition is not well understood. Herein, the evolution of the phonon modes in Li-intercalated 1T'-MoS 2 (Li x MoS 2 ) are investigated as a function of different 1T'-2H compositions. We observed that the strain evolution in the mixed phases is revealed by the softening of four Raman modes, B g ( J 1 ), A g ( J 3 ), E 1 2g , and A 1g , with increasing 1T' phase composition. Additionally, the first-order temperature coefficients of the 1T' phonon mode vary linearly with increasing 1T' composition, which is explained by increased electron-phonon and strain-phonon coupling.

  10. Measurement of T1 of human arterial and venous blood at 7T.

    PubMed

    Rane, Swati D; Gore, John C

    2013-04-01

    Techniques for measuring cerebral perfusion require accurate longitudinal relaxation (T1) of blood, an MRI parameter that is field dependent. T1 of arterial and venous human blood was measured at 7T using three different sources - pathology laboratory, blood bank and in vivo. The T1 of venous blood was measured from sealed samples from a pathology lab and in vivo. Samples from a blood bank were oxygenated and mixed to obtain different physiological concentrations of hematocrit and oxygenation. T1 relaxation times were estimated using a three-point fit to a simple inversion recovery equation. At 37°C, the T1 of blood at arterial pO2 was 2.29±0.1s and 2.07±0.12 at venous pO2. The in vivo T1 of venous blood, in three subjects, was slightly longer at 2.45±0.11s. T1 of arterial and venous blood at 7T was measured and found to be significantly different. The T1 values were longer in vivo than in vitro. While the exact cause for the discrepancy is unknown, the additives in the blood samples, degradation during experiment, oxygenation differences, and the non-stagnant nature of blood in vivo could be potential contributors to the lower values of T1 in the venous samples. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Validation of in vivo 2D displacements from spiral cine DENSE at 3T.

    PubMed

    Wehner, Gregory J; Suever, Jonathan D; Haggerty, Christopher M; Jing, Linyuan; Powell, David K; Hamlet, Sean M; Grabau, Jonathan D; Mojsejenko, Walter Dimitri; Zhong, Xiaodong; Epstein, Frederick H; Fornwalt, Brandon K

    2015-01-30

    Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. Due to the stimulated echo, the signal is inherently low and fades through the cardiac cycle. To compensate, a spiral acquisition has been used at 1.5T. This spiral sequence has not been validated at 3T, where the increased signal would be valuable, but field inhomogeneities may result in measurement errors. We hypothesized that spiral cine DENSE is valid at 3T and tested this hypothesis by measuring displacement errors at both 1.5T and 3T in vivo. Two-dimensional spiral cine DENSE and tagged imaging of the left ventricle were performed on ten healthy subjects at 3T and six healthy subjects at 1.5T. Intersection points were identified on tagged images near end-systole. Displacements from the DENSE images were used to project those points back to their origins. The deviation from a perfect grid was used as a measure of accuracy and quantified as root-mean-squared error. This measure was compared between 3T and 1.5T with the Wilcoxon rank sum test. Inter-observer variability of strains and torsion quantified by DENSE and agreement between DENSE and harmonic phase (HARP) were assessed by Bland-Altman analyses. The signal to noise ratio (SNR) at each cardiac phase was compared between 3T and 1.5T with the Wilcoxon rank sum test. The displacement accuracy of spiral cine DENSE was not different between 3T and 1.5T (1.2 ± 0.3 mm and 1.2 ± 0.4 mm, respectively). Both values were lower than the DENSE pixel spacing of 2.8 mm. There were no substantial differences in inter-observer variability of DENSE or agreement of DENSE and HARP between 3T and 1.5T. Relative to 1.5T, the SNR at 3T was greater by a factor of 1.4 ± 0.3. The spiral cine DENSE acquisition that has been used at 1.5T to measure cardiac displacements can be applied at 3T with equivalent accuracy. The inter-observer variability and agreement of DENSE-derived peak strains and

  12. Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells

    PubMed Central

    2013-01-01

    Background The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. Methods To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0–2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Results Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. Conclusions These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway

  13. Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells.

    PubMed

    Gwon, So Young; Ahn, Ji Yun; Jung, Chang Hwa; Moon, Bo Kyung; Ha, Tae Youl

    2013-08-06

    The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0-2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway during the early stages of adipogenesis.

  14. Reaction of the thermo-labile triazenide Na[tBu3SiNNNSiMe3] with CO2: formation of the imido carbonate (tBu3SiO)(Me3SiO)C[double bond, length as m-dash]N-SitBu3 and carbamine acid (tBu3SiO)CONH2.

    PubMed

    Lerner, H-W; Bolte, M; Wagner, M

    2017-07-11

    The thermo-labile triazenide Na[tBu 3 SiNNNSiMe 3 ] was prepared by the reaction of Me 3 SiN 3 with Na(thf) 2 [SitBu 3 ] in pentane at -78 °C. Treatment of Na[tBu 3 SiNNNSiMe 3 ] with an excess of carbon dioxide in pentane at -78 °C yielded the imido carbonate (tBu 3 SiO)(Me 3 SiO)C[double bond, length as m-dash]N-SitBu 3 and the carbamine acid (tBu 3 SiO)CONH 2 along with other products. From the reaction solution we could isolate the imido carbonate (tBu 3 SiO)(Me 3 SiO)C[double bond, length as m-dash]N-SitBu 3 and carbamine acid (tBu 3 SiO)CONH 2 . At first single crystals of the carbamine acid (tBu 3 SiO)CONH 2 (triclinic, space group P1[combining macron]) were grown from this solution at room temperature. A second crop of crystals were obtained by concentrating the solution. The second charge consisted of the imido carbonate (tBu 3 SiO)(Me 3 SiO)C[double bond, length as m-dash]N-SitBu 3 (monoclinic, space group P2 1 /n).

  15. [3T magnetic resonance T2 mapping for evaluation of cartilage repair after matrix-associated autologous chondrocyte transplantation].

    PubMed

    Zhang, Jun; Xu, Xian; Li, Xue; Chen, Min; Dong, Tian-Ming; Zuo, Pan-Li; An, Ning-Yu

    2015-01-01

    To assess the value of magnetic resonance imaging (MRI) T2 mapping in quantitative evaluation of cartilage repair following matrix-associated autologous chondrocyte transplantation (MACT). Six patients (with 9 plug cartilages) following MACT underwent MRI on a 3.0 Tesla MR scan system at 3, 6 and 12 months after the surgery. The full-thickness and zonal areas (deep and superficial layers) T2 values were calculated for the repaired cartilage and control cartilage. The mean T2 values of the repaired cartilage after MACT were significantly higher than that of the control cartilages at 3 and 6 months (P<0.05), but not at 12 months (P=0.063). At 6 and 12 months, the T2 values of the superficial layers were significantly higher than those of the deep layers in the repaired cartilages (P<0.05). The zonal (deep and superficial layers) T2 values of the repaired cartilages decreased significantly over time at 6 and 12 months as compared to those at 3 months after the surgery (P<0.05). MRI T2 mapping can serve as an important modality for assessing the repair of the articular cartilage following MACT.

  16. [Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers].

    PubMed

    Wang, Fu-long; Wan, De-sen; Lu, Zhen-hai; Fang, Yu-jing; Li, Li-ren; Chen, Gong; Wu, Xiao-jun; Ding, Pei-rong; Kong, Ling-heng; Lin, Jun-zhong; Pan, Zhi-zhong

    2013-04-01

    To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques. Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis. VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

  17. Accurate T1 mapping of short T2 tissues using a three-dimensional ultrashort echo time cones actual flip angle imaging-variable repetition time (3D UTE-Cones AFI-VTR) method.

    PubMed

    Ma, Ya-Jun; Lu, Xing; Carl, Michael; Zhu, Yanchun; Szeverenyi, Nikolaus M; Bydder, Graeme M; Chang, Eric Y; Du, Jiang

    2018-08-01

    To develop an accurate T 1 measurement method for short T 2 tissues using a combination of a 3-dimensional ultrashort echo time cones actual flip angle imaging technique and a variable repetition time technique (3D UTE-Cones AFI-VTR) on a clinical 3T scanner. First, the longitudinal magnetization mapping function of the excitation pulse was obtained with the 3D UTE-Cones AFI method, which provided information about excitation efficiency and B 1 inhomogeneity. Then, the derived mapping function was substituted into the VTR fitting to generate accurate T 1 maps. Numerical simulation and phantom studies were carried out to compare the AFI-VTR method with a B 1 -uncorrected VTR method, a B 1 -uncorrected variable flip angle (VFA) method, and a B 1 -corrected VFA method. Finally, the 3D UTE-Cones AFI-VTR method was applied to bovine bone samples (N = 6) and healthy volunteers (N = 3) to quantify the T 1 of cortical bone. Numerical simulation and phantom studies showed that the 3D UTE-Cones AFI-VTR technique provides more accurate measurement of the T 1 of short T 2 tissues than the B 1 -uncorrected VTR and VFA methods or the B 1 -corrected VFA method. The proposed 3D UTE-Cones AFI-VTR method showed a mean T 1 of 240 ± 25 ms for bovine cortical bone and 218 ± 10 ms for the tibial midshaft of human volunteers, respectively, at 3T. The 3D UTE-Cones AFI-VTR method can provide accurate T 1 measurements of short T 2 tissues such as cortical bone. Magn Reson Med 80:598-608, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  18. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping at 3T MRI of the wrist: Feasibility and clinical application.

    PubMed

    Rehnitz, Christoph; Klaan, Bastian; Burkholder, Iris; von Stillfried, Falko; Kauczor, Hans-Ulrich; Weber, Marc-André

    2017-02-01

    To assess the feasibility of delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T 2 mapping for biochemical imaging of the wrist at 3T. Seventeen patients with wrist pain (mean age, 41.4 ± 13.1 years) including a subgroup with chondromalacia (n = 11) and 15 healthy volunteers (26.0 ± 2.2 years) underwent dGEMRIC and T 2 mapping at 3T. For dGEMRIC, the optimum time window after contrast-injection (gadopentetate dimeglumine) was defined as the plateau of the T 1 curve of repeated measurements 15-90 minutes postinjection and assessed in all volunteers. Reference values of healthy-appearing cartilage from all individuals and values in areas of chondromalacia were assessed using region-of-interest analyses. Receiver-operating-characteristic analyses were applied to assess discriminatory ability between damaged and normal cartilage. The optimum time window was 45-90 minutes, and the 60-minute timepoint was subsequently used. In chondromalacia, dGEMRIC values were lower (551 ± 84 msec, P < 0.001), and T 2 values higher (63.9 ± 17.7, P = 0.001) compared to healthy-appearing cartilage of the same patient. Areas under the curve did not significantly differ between dGEMRIC (0.91) and T 2 mapping (0.99; P = 0.17). In healthy-appearing cartilage of volunteers and patients, mean dGEMRIC values were 731.3 ± 47.1 msec and 674.6 ± 72.1 msec (P = 0.01), and mean T 2 values were 36.5 ± 5 msec and 41.1 ± 3.2 msec (P = 0.009), respectively. At 3T, dGEMRIC and T 2 mapping are feasible for biochemical cartilage imaging of the wrist. Both techniques allow separation and biochemical assessment of thin opposing cartilage surfaces and can distinguish between healthy and damaged cartilage. 3 J. Magn. Reson. Imaging 2017;45:381-389. © 2016 International Society for Magnetic Resonance in Medicine.

  19. T1- or T2-weighted magnetic resonance imaging: what is the best choice to evaluate atrophy of the hippocampus?

    PubMed

    Fischbach-Boulanger, C; Fitsiori, A; Noblet, V; Baloglu, S; Oesterle, H; Draghici, S; Philippi, N; Duron, E; Hanon, O; Dietemann, J-L; Blanc, F; Kremer, S

    2018-05-01

    Magnetic resonance imaging is part of the diagnostic criteria for Alzheimer's disease (AD) through the evaluation of hippocampal atrophy. The objective of this study was to evaluate which sequence of T1-weighted (T1WI) and T2-weighted (T2WI) imaging allowed the best visual evaluation of hippocampal atrophy. Visual qualitative ratings of the hippocampus of 100 patients with mild cognitive impairment (MCI) and 50 patients with AD were made independently by four operators according to the medial temporal lobe atrophy score based either on T1WI or T2WI. These two evaluations were compared in terms of interobserver reproducibility, concordance with a quantitative volumetric measure, discrimination power between AD and MCI groups, and correlation with several neuropsychological tests. The medial temporal lobe atrophy score evaluated on either T1WI or T2WI exhibited similar interobserver variability and accordance with quantitative volumetric evaluation. However, the visual evaluation on T2WI seemed to provide better discrimination power between AD and MCI groups for both left (T1WI, P = 0.0001; T2WI, P = 7.072 × 10 -5 ) and right (T1WI, P = 0.008; T2WI, P = 0.001) hippocampus, and a higher overall correlation with neuropsychological tests. The present study suggests that T2WI provides a more adequate visual rating of hippocampal atrophy. © 2018 EAN.

  20. Cardiac MOLLI T1 mapping at 3.0 T: comparison of patient-adaptive dual-source RF and conventional RF transmission.

    PubMed

    Rasper, Michael; Nadjiri, Jonathan; Sträter, Alexandra S; Settles, Marcus; Laugwitz, Karl-Ludwig; Rummeny, Ernst J; Huber, Armin M

    2017-06-01

    To prospectively compare image quality and myocardial T 1 relaxation times of modified Look-Locker inversion recovery (MOLLI) imaging at 3.0 T (T) acquired with patient-adaptive dual-source (DS) and conventional single-source (SS) radiofrequency (RF) transmission. Pre- and post-contrast MOLLI T 1 mapping using SS and DS was acquired in 27 patients. Patient wise and segment wise analysis of T 1 times was performed. The correlation of DS MOLLI measurements with a reference spin echo sequence was analysed in phantom experiments. DS MOLLI imaging reduced T 1 standard deviation in 14 out of 16 myocardial segments (87.5%). Significant reduction of T 1 variance could be obtained in 7 segments (43.8%). DS significantly reduced myocardial T 1 variance in 16 out of 25 patients (64.0%). With conventional RF transmission, dielectric shading artefacts occurred in six patients causing diagnostic uncertainty. No according artefacts were found on DS images. DS image findings were in accordance with conventional T 1 mapping and late gadolinium enhancement (LGE) imaging. Phantom experiments demonstrated good correlation of myocardial T 1 time between DS MOLLI and spin echo imaging. Dual-source RF transmission enhances myocardial T 1 homogeneity in MOLLI imaging at 3.0 T. The reduction of signal inhomogeneities and artefacts due to dielectric shading is likely to enhance diagnostic confidence.

  1. Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting.

    PubMed

    Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

    2015-12-01

    Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T 1 and T 2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T 1 and T 2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T 1 and T 2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored.

  2. Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting

    PubMed Central

    Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

    2016-01-01

    Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T1 and T2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T1 and T2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T1 and T2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored. PMID:26824078

  3. Colorectal carcinoma: Ex vivo evaluation using 3-T high-spatial-resolution quantitative T2 mapping and its correlation with histopathologic findings.

    PubMed

    Yamada, Ichiro; Yoshino, Norio; Hikishima, Keigo; Miyasaka, Naoyuki; Yamauchi, Shinichi; Uetake, Hiroyuki; Yasuno, Masamichi; Saida, Yukihisa; Tateishi, Ukihide; Kobayashi, Daisuke; Eishi, Yoshinobu

    2017-05-01

    In this study, we aimed to evaluate the feasibility of determining the mural invasion depths of colorectal carcinomas using high-spatial-resolution (HSR) quantitative T2 mapping on a 3-T magnetic resonance (MR) scanner. Twenty colorectal specimens containing adenocarcinomas were imaged on a 3-T MR system equipped with a 4-channel phased-array surface coil. HSR quantitative T2 maps were acquired using a spin-echo sequence with a repetition time/echo time of 7650/22.6-361.6ms (16 echoes), 87×43.5-mm field of view, 2-mm section thickness, 448×224 matrix, and average of 1. HSR fast-spin-echo T2-weighted images were also acquired. Differences between the T2 values (ms) of the tumor tissue, colorectal wall layers, and fibrosis were measured, and the MR images and histopathologic findings were compared. In all specimens (20/20, 100%), the HSR quantitative T2 maps clearly depicted an 8-layer normal colorectal wall in which the T2 values of each layer differed from those of the adjacent layer(s) (P<0.001). Using this technique, fibrosis (73.6±9.4ms) and tumor tissue (104.2±6.4ms) could also be clearly differentiated (P<0.001). In 19 samples (95%), the HSR quantitative T2 maps and histopathologic data yielded the same findings regarding the tumor invasion depth. Our results indicate that 3-T HSR quantitative T2 mapping is useful for distinguishing colorectal wall layers and differentiating tumor and fibrotic tissues. Accordingly, this technique could be used to determine mural invasion by colorectal carcinomas with a high level of accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells

    PubMed Central

    Weiss, Jonathan M.; Bilate, Angelina M.; Gobert, Michael; Ding, Yi; Curotto de Lafaille, Maria A.; Parkhurst, Christopher N.; Xiong, Huizhong; Dolpady, Jayashree; Frey, Alan B.; Ruocco, Maria Grazia; Yang, Yi; Floess, Stefan; Huehn, Jochen; Oh, Soyoung; Li, Ming O.; Niec, Rachel E.; Rudensky, Alexander Y.; Dustin, Michael L.; Littman, Dan R.

    2012-01-01

    Foxp3 activity is essential for the normal function of the immune system. Two types of regulatory T (T reg) cells express Foxp3, thymus-generated natural T reg (nT reg) cells, and peripherally generated adaptive T reg (iT reg) cells. These cell types have complementary functions. Until now, it has not been possible to distinguish iT reg from nT reg cells in vivo based solely on surface markers. We report here that Neuropilin 1 (Nrp1) is expressed at high levels by most nT reg cells; in contrast, mucosa-generated iT reg and other noninflammatory iT reg cells express low levels of Nrp1. We found that Nrp1 expression is under the control of TGF-β. By tracing nT reg and iT reg cells, we could establish that some tumors have a very large proportion of infiltrating iT reg cells. iT reg cells obtained from highly inflammatory environments, such as the spinal cords of mice with spontaneous autoimmune encephalomyelitis (EAE) and the lungs of mice with chronic asthma, express Nrp1. In the same animals, iT reg cells in secondary lymphoid organs remain Nrp1low. We also determined that, in spontaneous EAE, iT reg cells help to establish a chronic phase of the disease. PMID:22966001

  5. Sustained Benefit Lasting One Year from T4 Instead of T3-T4 Sympathectomy for Isolated Axillary Hyperhidrosis

    PubMed Central

    Munia, Marco Antonio S.; Wolosker, Nelson; Kaufmann, Paulo; de Campos, José Ribas Milanes; Puech-Leão, Pedro

    2008-01-01

    INTRODUCTION Level T4 video-assisted thoracoscopic sympathectomy proved superior to T3-T4 treatment for controlling axillary hyperhidrosis at the initial and six-month follow-ups of these patients. OBJECTIVE To compare the results of two levels of sympathectomy (T3-T4 vs. T4) for treating axillary sudoresis over one year of follow-up. METHODS Sixty-four patients with axillary hyperhidrosis were randomized to denervation of T3-T4 or T4 alone and followed prospectively. All patients were examined preoperatively and were followed postoperatively for one year. Axillary hyperhidrosis treatment was evaluated, along with the presence, location, and severity of compensatory hyperhidrosis and self-reported quality of life. RESULTS According to patient reports after one year, all cases of axillary hyperhidrosis were successfully treated by surgery. There were no instances of treatment failure. After six months, compensatory hyperhidrosis was present in 27 patients of the T3-T4 group (87.1%) and in 16 patients of the T4 group (48.5%). After one year, all T3-T4 patients experienced some degree of compensatory hyperhidrosis, compared to only 14 patients in the T4 group (42.4%). In addition, compensatory hyperhidrosis was less severe in the T4 patients (p < 0.01). Quality of life was poor before surgery, and it improved in both groups at six months and one year of follow-up (p = 0.002). There were no cases of mortality, no significant postoperative complications, and no need for conversion to thoracotomy in either group. CONCLUSION Both techniques were effective for treating axillary hyperhidrosis, but the T4 group showed milder compensatory hyperhidrosis and greater patient satisfaction at the one-year follow-up. PMID:19060999

  6. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon.

    PubMed

    Kendig, Derek M; Hurst, Norman R; Bradley, Zachary L; Mahavadi, Sunila; Kuemmerle, John F; Lyall, Vijay; DeSimone, John; Murthy, Karnam S; Grider, John R

    2014-12-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5'-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1(-/-) mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. Copyright © 2014 the American Physiological Society.

  7. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

    PubMed Central

    Kendig, Derek M.; Hurst, Norman R.; Bradley, Zachary L.; Mahavadi, Sunila; Kuemmerle, John F.; Lyall, Vijay; DeSimone, John; Murthy, Karnam S.

    2014-01-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5′-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1−/− mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. PMID:25324508

  8. Treat-to-target (T2T) recommendations for gout.

    PubMed

    Kiltz, U; Smolen, J; Bardin, T; Cohen Solal, A; Dalbeth, N; Doherty, M; Engel, B; Flader, C; Kay, J; Matsuoka, M; Perez-Ruiz, F; da Rocha Castelar-Pinheiro, G; Saag, K; So, A; Vazquez Mellado, J; Weisman, M; Westhoff, T H; Yamanaka, H; Braun, J

    2017-04-01

    The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. NMR relaxation in natural soils: Fast Field Cycling and T1-T2 Determination by IR-MEMS

    NASA Astrophysics Data System (ADS)

    Haber-Pohlmeier, S.; Pohlmeier, A.; Stapf, S.; van Dusschoten, D.

    2009-04-01

    Soils are natural porous media of highest importance for food production and sustainment of water resources. For these functions, prominent properties are their ability of water retainment and transport, which are mainly controlled by pore size distribution. The latter is related to NMR relaxation times of water molecules, of which the longitudinal relaxation time can be determined non-invasively by fast-field cycling relaxometry (FFC) and both are obtainable by inversion recovery - multi-echo- imaging (IR-MEMS) methods. The advantage of the FFC method is the determination of the field dependent dispersion of the spin-lattice relaxation rate, whereas MRI at high field is capable of yielding spatially resolved T1 and T2 times. Here we present results of T1- relaxation time distributions of water in three natural soils, obtained by the analysis of FFC data by means of the inverse Laplace transformation (CONTIN)1. Kaldenkirchen soil shows relatively broad bimodal distribution functions D(T1) which shift to higher relaxation rates with increasing relaxation field. These data are compared to spatially resolved T1- and T2 distributions, obtained by IR-MEMS. The distribution of T1 corresponds well to that obtained by FFC.

  10. A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).

    PubMed

    Yoshida, Naohiro; Kinugasa, Tetsushi; Miyoshi, Hiroaki; Sato, Kensaku; Yuge, Kotaro; Ohchi, Takafumi; Fujino, Shinya; Shiraiwa, Sachiko; Katagiri, Mitsuhiro; Akagi, Yoshito; Ohshima, Koichi

    2016-03-01

    Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.

  11. T1 hyperintense disc in alkaptonuria.

    PubMed

    Sag, Alan A; Silbergleit, Richard; Olson, Rick E; Wilson, Jon; Krishnan, Anant

    2012-10-01

    Case report. To report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation. A 46-year-old man without previous diagnosis of alkaptonuria underwent evaluation for progressive back pain revealing a T1-hyperintense disc herniation at the L3-L4 level. Discectomy recovered a blackened disc that was pathologically confirmed to be nucleus pulposus with alkaptonuric involvement. The differential diagnosis of a T1-hyperintense, T2-hypointense disc on magnetic resonance imaging is discussed, with emphasis on the pathophysiology of alkaptonuria. A single patient is reported. Pathologically proven patient presentation with radiological and pathological images. We report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation.

  12. 7T MRI subthalamic nucleus atlas for use with 3T MRI.

    PubMed

    Milchenko, Mikhail; Norris, Scott A; Poston, Kathleen; Campbell, Meghan C; Ushe, Mwiza; Perlmutter, Joel S; Snyder, Abraham Z

    2018-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in most patients with Parkinson disease (PD), yet may produce untoward effects. Investigation of DBS effects requires accurate localization of the STN, which can be difficult to identify on magnetic resonance images collected with clinically available 3T scanners. The goal of this study is to develop a high-quality STN atlas that can be applied to standard 3T images. We created a high-definition STN atlas derived from seven older participants imaged at 7T. This atlas was nonlinearly registered to a standard template representing 56 patients with PD imaged at 3T. This process required development of methodology for nonlinear multimodal image registration. We demonstrate mm-scale STN localization accuracy by comparison of our 3T atlas with a publicly available 7T atlas. We also demonstrate less agreement with an earlier histological atlas. STN localization error in the 56 patients imaged at 3T was less than 1 mm on average. Our methodology enables accurate STN localization in individuals imaged at 3T. The STN atlas and underlying 3T average template in MNI space are freely available to the research community. The image registration methodology developed in the course of this work may be generally applicable to other datasets.

  13. Simultaneous Measurement of T2 and Apparent Diffusion Coefficient (T2+ADC) in the Heart With Motion-Compensated Spin Echo Diffusion-Weighted Imaging

    PubMed Central

    Aliotta, Eric; Moulin, Kévin; Zhang, Zhaohuan; Ennis, Daniel B.

    2018-01-01

    Purpose To evaluate a technique for simultaneous quantitative T2 and apparent diffusion coefficient (ADC) mapping in the heart (T2+ADC) using spin echo (SE) diffusion-weighted imaging (DWI). Theory and Methods T2 maps from T2+ADC were compared with single-echo SE in phantoms and with T2-prepared (T2-prep) balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps from T2+ADC were compared with conventional DWI in phantoms and in vivo. T2+ADC was also demonstrated in a patient with acute myocardial infarction (MI). Results Phantom T2 values from T2+ADC were closer to a single-echo SE reference than T2-prep bSSFP (−2.3 ± 6.0% vs 22.2 ± 16.3%; P < 0.01), and ADC values were in excellent agreement with DWI (0.28 ± 0.4%). In volunteers, myocardial T2 values from T2+ADC were significantly shorter than T2-prep bSSFP (35.8 ± 3.1 vs 46.8 ± 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.) different between T2+ADC and conventional motion-compensated DWI (1.39 ± 0.18 vs 1.38 ± 0.18 mm2/ms; P = N.S.). In the patient, T2 and ADC were both significantly elevated in the infarct compared with remote myocardium (T2: 40.4 ± 7.6 vs 56.8 ± 22.0; P < 0.01; ADC: 1.47 ± 0.59 vs 1.65 ± 0.65 mm2/ms; P < 0.01). Conclusion T2+ADC generated coregistered, free-breathing T2 and ADC maps in healthy volunteers and a patient with acute MI with no cost in accuracy, precision, or scan time compared with DWI. PMID:28516485

  14. Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio in the cerebral cortex.

    PubMed

    Ritchie, Jacob; Pantazatos, Spiro P; French, Leon

    2018-07-01

    Magnetic resonance (MR) images of the brain are of immense clinical and research utility. At the atomic and subatomic levels, the sources of MR signals are well understood. However, we lack a comprehensive understanding of the macromolecular correlates of MR signal contrast. To address this gap, we used genome-wide measurements to correlate gene expression with MR signal intensity across the cerebral cortex in the Allen Human Brain Atlas (AHBA). We focused on the ratio of T1-weighted and T2-weighted intensities (T1-w/T2-w ratio image), which is considered to be a useful proxy for myelin content. As expected, we found enrichment of positive correlations between myelin-associated genes and the ratio image, supporting its use as a myelin marker. Genome-wide, there was an association with protein mass, with genes coding for heavier proteins expressed in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly correlated with the T1-w/T2-w ratio, but this was not driven by myelin-associated genes. Mitochondrial genes exhibit the strongest relationship, showing higher expression in regions with low T1-w/T2-w ratio. This may be due to the pH gradient in mitochondria as genes up-regulated by pH in the brain were also highly correlated with the ratio. While we corroborate associations with myelin and synaptic plasticity, differences in the T1-w/T2-w ratio across the cortex are more strongly linked to molecule size, oligodendrocyte markers, mitochondria, and pH. We evaluate correlations between AHBA transcriptomic measurements and a group averaged T1-w/T2-w ratio image, showing agreement with in-sample results. Expanding our analysis to the whole brain results in strong positive T1-w/T2-w correlations for immune system, inflammatory disease, and microglia marker genes. Genes with negative correlations were enriched for neuron markers and synaptic plasticity genes. Lastly, our findings are similar when performed on T1-w or inverted T2-w intensities alone

  15. Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia.

    PubMed

    Nagel, Stefan; Pommerenke, Claudia; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G; MacLeod, Roderick A F

    2016-07-19

    Recently, we identified deregulated expression of the B-cell specific transcription factor MEF2C in T-cell acute lymphoid leukemia (T-ALL). Here, we performed sequence analysis of a regulatory upstream section of MEF2C in T-ALL cell lines which, however, proved devoid of mutations. Unexpectedly, we found strong conservation between the regulatory upstream region of MEF2C (located at chromosomal band 5q14) and an intergenic stretch at 7q11 located between STAG3L4 and AUTS2, covering nearly 20 kb. While the non-coding gene STAG3L4 was inconspicuously expressed, AUTS2 was aberrantly upregulated in 6% of T-ALL patients (public dataset GSE42038) and in 3/24 T-ALL cell lines, two of which represented very immature differentiation stages. AUTS2 expression was higher in normal B-cells than in T-cells, indicating lineage-specific activity in lymphopoiesis. While excluding chromosomal aberrations, examinations of AUTS2 transcriptional regulation in T-ALL cells revealed activation by IL7-IL7R-STAT5-signalling and MEF2C. AUTS2 protein has been shown to interact with polycomb repressor complex 1 subtype 5 (PRC1.5), transforming this particular complex into an activator. Accordingly, expression profiling and functional analyses demonstrated that AUTS2 activated while PCGF5 repressed transcription of NKL homeobox gene MSX1 in T-ALL cells. Forced expression and pharmacological inhibition of EZH2 in addition to H3K27me3 analysis indicated that PRC2 repressed MSX1 as well. Taken together, we found that AUTS2 and MEF2C, despite lying on different chromosomes, share strikingly similar regulatory upstream regions and aberrant expression in T-ALL subsets. Our data implicate chromatin complexes PRC1/AUTS2 and PRC2 in a gene network in T-ALL regulating early lymphoid differentiation.

  16. Breath-hold black-blood T1rho mapping improves liver T1rho quantification in healthy volunteers.

    PubMed

    Wáng, Yì Xiáng J; Deng, Min; Lo, Gladys G; Liang, Dong; Yuan, Jing; Chen, Weitian

    2018-03-01

    Background Recent researches suggest that T1rho may be a non-invasive and quantitative technique for detecting and grading liver fibrosis. Purpose To compare a multi-breath-hold bright-blood fast gradient echo (GRE) imaging and a single breath-hold single-shot fast spin echo (FSE) imaging with black-blood effect for liver parenchyma T1rho measurement and to study liver physiological T1rho value in healthy volunteers. Material and Methods The institutional Ethics Committee approved this study. 28 healthy participants (18 men, 10 women; age = 29.6 ± 5.1 years) underwent GRE liver T1rho imaging, and 20 healthy participants (10 men, 10 women; age = 36.9 ± 10.3 years) underwent novel black-blood FSE liver T1rho imaging, both at 3T with spin-lock frequency of 500 Hz. The FSE technique allows simultaneous acquisition of four spin lock times (TSLs; 1 ms, 10 ms, 30 ms, 50msec) in 10 s. Results For FSE technique the intra-scan repeatability intraclass correlation coefficient (ICC) was 0.98; while the inter-scan reproducibility ICC was 0.82 which is better than GRE technique's 0.76. Liver T1rho value in women tended to have a higher value than T1rho values in men (FSE: 42.28 ± 4.06 ms for women and 39.13 ± 2.12 ms for men; GRE: 44.44 ± 1.62 ms for women and 42.36 ± 2.00 ms for men) and FSE technique showed liver T1rho value decreased slightly as age increased. Conclusion Single breath-hold black-blood FSE sequence has better scan-rescan reproducibility than multi-breath-hold bright-blood GRE sequence. Gender and age dependence of liver T1rho in healthy participants is observed, with young women tending to have a higher T1rho measurement.

  17. Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory.

    PubMed

    Sindreu, Carlos; Palmiter, Richard D; Storm, Daniel R

    2011-02-22

    The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory.

  18. The effect of myostatin on proliferation and lipid accumulation in 3T3-L1 preadipocytes.

    PubMed

    Zhu, Hui Juan; Pan, Hui; Zhang, Xu Zhe; Li, Nai Shi; Wang, Lin Jie; Yang, Hong Bo; Gong, Feng Ying

    2015-06-01

    Myostatin is a critical negative regulator of skeletal muscle development, and has been reported to be involved in the progression of obesity and diabetes. In the present study, we explored the effects of myostatin on the proliferation and differentiation of 3T3-L1 preadipocytes by using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide spectrophotometry, intracellular triglyceride (TG) assays, and real-time quantitative RT-PCR methods. The results indicated that recombinant myostatin significantly promoted the proliferation of 3T3-L1 preadipocytes and the expression of proliferation-related genes, including Cyclin B2, Cyclin D1, Cyclin E1, Pcna, and c-Myc, and IGF1 levels in the medium of 3T3-L1 were notably upregulated by 35.2, 30.5, 20.5, 33.4, 51.2, and 179% respectively (all P<0.01) in myostatin-treated 3T3-L1 cells. Meanwhile, the intracellular lipid content of myostatin-treated cells was notably reduced as compared with the non-treated cells. Additionally, the mRNA levels of Pparγ, Cebpα, Gpdh, Dgat, Acs1, Atgl, and Hsl were significantly downregulated by 22-76% in fully differentiated myostatin-treated adipocytes. Finally, myostatin regulated the mRNA levels and secretion of adipokines, including Adiponectin, Resistin, Visfatin, and plasminogen activator inhibitor-1 (PAI-1) in 3T3-L1 adipocytes (all P<0.001). Above all, myostatin promoted 3T3-L1 proliferation by increasing the expression of cell-proliferation-related genes and by stimulating IGF1 secretion. Myostatin inhibited 3T3-L1 adipocyte differentiation by suppressing Pparγ and Cebpα expression, which consequently deceased lipid accumulation in 3T3-L1 cells by inhibiting the expression of critical lipogenic enzymes and by promoting the expression of lipolytic enzymes. Finally, myostatin modulated the expression and secretion of adipokines in fully differentiated 3T3-L1 adipocytes. © 2015 Society for Endocrinology.

  19. Breast MRI at 3.0 T in a high-risk familial breast cancer screening cohort: comparison with 1.5 T screening studies.

    PubMed

    Pickles, M D; Turnbull, L W

    2012-07-01

    The sensitivity of X-ray mammography for the detection of breast malignancy in younger females is lower than that of breast MRI; consequently, guidelines recommend annual MRI for patients with a significantly elevated lifetime risk. The improved signal-to-noise ratio obtainable at 3.0 T should result in data superior to those obtainable at 1.5 T. However, breast imaging on higher field strength systems poses specific problems. As a result, caution has been urged in the implementation of breast MRI at 3.0 T. The aim of this study was to determine if it is appropriate to use 3.0 T MRI in the screening of patients by comparing the summary statistics achieved by this 3.0 T MRI programme against the published results of 1.5 T screening studies. Over a 20-month period, 291 patients referred with an elevated familial risk of breast cancer were examined at 3.0 T. Resulting images were scored based on the Royal College of Radiologists Breast Group imaging classification. The reference standard was a combination of histology and follow-up imaging. Follow-up data were available in 267 patients. Analysis revealed positive and negative post-test probabilities of 28% [95% confidence intervals (CI); range, 10-60%] and 1% (95% CI; range, 0-2%), respectively. These results compared favourably against those of a recent meta-analysis [25.3% (95% CI; range, 18.4-33.8%) and 0.4% (95% CI; range, 0.2-0.9%), respectively]. Given the similar summary statistics between this work and the 1.5 T results, it would appear that screening of high-risk patients at 3.0 T has potential. Further studies should be undertaken to verify this result.

  20. APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome.

    PubMed

    Miller, Michael; Rhyne, Jeffrey; Chen, Hegang; Beach, Valerie; Ericson, Richard; Luthra, Kalpana; Dwivedi, Manjari; Misra, Anoop

    2007-05-01

    Despite the growing epidemic of the metabolic syndrome (MetS), few studies have evaluated genetic polymorphisms associated with the MetS phenotype. One candidate, APOC3, modulates lipid and lipoprotein metabolism and the promoter polymorphisms C-482T/T-455C are associated with loss of insulin downregulation. One hundred twenty two consecutive MetS cases were matched by age, sex and race in a 1:1 case-control design to evaluate the prevalence of common polymorphisms in the following candidate genes: APOC3, APOE, B3AR, FABP2, GNB3, LPL, and PPARalpha and PPARgamma. Compared to controls, MetS subjects exhibited a greater prevalence of APOC3 promoter polymorphisms. Specifically, the frequency of the variant C-482T and T-455C alleles was 70.5 and 81.9% of cases compared to 43.4 and 54.1% in controls, respectively (p <0.0001). Overall, APOC3 promoter variants were associated with a greater likelihood of MetS compared to wild type [C-482T (OR: 4.3; 95% CI: 2.2, 8.6 [p <0.0001]), T-455C (OR: 3.6; 95% CI: 2.0, 6.7 [p <0.0001])]. No material differences were identified between the other genetic variants tested and prevalence of MetS. These data, therefore, suggest that the APOC3 promoter polymorphisms C-482T and T-455C are associated with the MetS.

  1. Roles of Three Transporters, CbcXWV, BetT1, and BetT3, in Pseudomonas aeruginosa Choline Uptake for Catabolism ▿ †

    PubMed Central

    Malek, Adel A.; Chen, Chiliang; Wargo, Matthew J.; Beattie, Gwyn A.; Hogan, Deborah A.

    2011-01-01

    Pseudomonas aeruginosa uses the quaternary amine choline as a carbon source, osmoprotectant, and macromolecular precursor. The importance of choline in P. aeruginosa physiology is highlighted by the presence of multiple known and putative choline transporters encoded within its genome. This report describes the relative roles of three choline transporters, the ABC transporter CbcXWV and two symporters, BetT1 and BetT3, in P. aeruginosa growth on choline under osmotic conditions that are physiologically relevant to eukaryotic hosts. The increased lag phases exhibited by the ΔbetT1 and ΔbetT1 ΔbetT3 mutants relative to the wild type upon transfer to medium with choline as a sole carbon source suggested roles for BetT1 and BetT3 in cells newly exposed to choline. BetT3 and CbcXWV, but not BetT1, were sufficient to support growth on choline. betT1 and betT3 expression was regulated by the repressor BetI and choline, whereas cbcXWV expression was induced by the activator GbdR and glycine betaine. The data support a model in which, upon transfer to a choline-based medium, the glycine betaine derived from choline taken up by BetT1 and BetT3 promotes subsequent GbdR-mediated cbcXWV induction. Furthermore, growth data indicated that the relative contributions of each transporter varied under different conditions, as BetT1 and CbcXWV were the primary choline transporters under hypo-osmolar conditions whereas BetT3 was the major choline transporter under hyperosmolar conditions. This work represents the first systematic approach to unravel the mechanisms of choline uptake in P. aeruginosa, which has the most complex bacterial choline uptake systems characterized to date. PMID:21478341

  2. Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma

    PubMed Central

    Ome, Yusuke; Hashida, Kazuki; Yokota, Mitsuru; Nagahisa, Yoshio; Okabe, Michio; Kawamoto, Kazuyuki

    2017-01-01

    AIM To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC). METHODS We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach. RESULTS The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence. CONCLUSION LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results. PMID:28465640

  3. Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma.

    PubMed

    Ome, Yusuke; Hashida, Kazuki; Yokota, Mitsuru; Nagahisa, Yoshio; Okabe, Michio; Kawamoto, Kazuyuki

    2017-04-14

    To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC). We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach. The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence. LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results.

  4. Inhibitory effects of LPA1 on cell motile activities stimulated by hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone in fibroblast 3T3 cells.

    PubMed

    Hirane, Miku; Araki, Mutsumi; Dong, Yan; Honoki, Kanya; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

    2013-11-08

    Reactive oxygen species (ROS) are known to mediate a variety of biological responses, including cell motility. Recently, we indicated that lysophosphatidic acid (LPA) receptor-3 (LPA3) increased cell motile activity stimulated by hydrogen peroxide. In the present study, we assessed the role of LPA1 in the cell motile activity mediated by ROS in mouse fibroblast 3T3 cells. 3T3 cells were treated with hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) at concentrations of 0.1 and 1 μM for 48 h. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3 cells treated with hydrogen peroxide and DMNQ were significantly higher than those of untreated cells. 3T3 cells treated with hydrogen peroxide and DMNQ showed elevated expression levels of the Lpar3 gene, but not the Lpar1 and Lpar2 genes. To investigate the effects of LPA1 on the cell motile activity induced by hydrogen peroxide and DMNQ, Lpar1-overexpressing (3T3-a1) cells were generated from 3T3 cells and treated with hydrogen peroxide and DMNQ. The cell motile activities stimulated by hydrogen peroxide and DMNQ were markedly suppressed in 3T3-a1 cells. These results suggest that LPA signaling via LPA1 inhibits the cell motile activities stimulated by hydrogen peroxide and DMNQ in 3T3 cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Spectroscopic Studies of Perturbed T1 Cu Sites in the Multicopper Oxidases Saccharomyces Cerevisiae Fet3p And Rhus Vernicifera Laccase: Allosteric Coupling Between the T1 And Trinuclear Cu Sites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Augustine, A.J.; Kragh, M.E.; Sarangi, R.

    2009-04-30

    The multicopper oxidases catalyze the 4e{sup -} reduction of O{sub 2} to H{sub 2}O coupled to the 1e{sup -} oxidation of 4 equiv of substrate. This activity requires four Cu atoms, including T1, T2, and coupled binuclear T3 sites. The T2 and T3 sites form a trinuclear cluster (TNC) where O{sub 2} is reduced. The T1 is coupled to the TNC through a T1-Cys-His-T3 electron transfer (ET) pathway. In this study the two T3 Cu coordinating His residues which lie in this pathway in Fet3 have been mutated, H483Q, H483C, H485Q, and H485C, to study how perturbation at the TNCmore » impacts the T1 Cu site. Spectroscopic methods, in particular resonance Raman (rR), show that the change from His to Gln to Cys increases the covalency of the T1 Cu?S Cys bond and decreases its redox potential. This study of T1?TNC interactions is then extended to Rhus vernicifera laccase where a number of well-defined species including the catalytically relevant native intermediate (NI) can be trapped for spectroscopic study. The T1 Cu?S covalency and potential do not change in these species relative to resting oxidized enzyme, but interestingly the differences in the structure of the TNC in these species do lead to changes in the T1 Cu rR spectrum. This helps to confirm that vibrations in the cysteine side chain of the T1 Cu site and the protein backbone couple to the Cu?S vibration. These changes in the side chain and backbone provide a possible mechanism for regulating intramolecular T1 to TNC ET in NI and partially reduced enzyme forms for efficient turnover.« less

  6. T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

    PubMed

    Greulich, Simon; Mayr, Agnes; Kitterer, Daniel; Latus, Joerg; Henes, Joerg; Steubing, Hannah; Kaesemann, Philipp; Patrascu, Alexandru; Greiser, Andreas; Groeninger, Stefan; Braun, Niko; Alscher, M Dominik; Sechtem, Udo; Mahrholdt, Heiko

    2017-01-06

    Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

  7. Tuning the relaxation rates of dual-mode T1/T2 nanoparticle contrast agents: a study into the ideal system

    NASA Astrophysics Data System (ADS)

    Keasberry, Natasha A.; Bañobre-López, Manuel; Wood, Christopher; Stasiuk, Graeme. J.; Gallo, Juan; Long, Nicholas. J.

    2015-09-01

    Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in

  8. The influence of microvascular injury on native T1 and T2* relaxation values after acute myocardial infarction: implications for non-contrast-enhanced infarct assessment.

    PubMed

    Robbers, Lourens F H J; Nijveldt, Robin; Beek, Aernout M; Teunissen, Paul F A; Hollander, Maurits R; Biesbroek, P Stefan; Everaars, Henk; van de Ven, Peter M; Hofman, Mark B M; van Royen, Niels; van Rossum, Albert C

    2018-02-01

    Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI. Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium. Average T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p<0.001). The presence of MVI profoundly affects MOLLI-measured native T1 values. T2* mapping suggested that this may be the result of intramyocardial haemorrhage. These findings have important implications for the interpretation of native T1 values shortly after AMI. • Microvascular injury after acute myocardial infarction affects local T1 and T2* values. • Infarct zone T1 values are lower if microvascular injury is present. • T2* mapping suggests that low infarct T1 values are likely haemorrhage. • T1 and T2* values are complimentary for correctly assessing post-infarct myocardium.

  9. Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory

    PubMed Central

    Sindreu, Carlos; Palmiter, Richard D.; Storm, Daniel R.

    2011-01-01

    The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory. PMID:21245308

  10. Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application

    NASA Astrophysics Data System (ADS)

    Tegafaw, Tirusew; Xu, Wenlong; Wasi Ahmad, Md; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho

    2015-09-01

    A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd3+ (8S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy3+ (6H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd3+ and Dy3+ and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

  11. Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression.

    PubMed

    Li, Jin-Lian; Xiong, Kang-Hui; Dong, Yu-Lin; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

    2003-08-18

    Vesicular glutamate transporters are responsible for glutamate transport into synaptic vesicles. In the present study, we examined immunohistochemically the expression of vesicular glutamate transporters, VGluT1 and VGluT2, in trigeminal ganglion neurons of the rat. Immunohistochemistry for VGluT1 and VGluT2 indicated that more than 80% of trigeminal ganglion neurons express VGluT1 and/or VGluT2 in their cell bodies. It also indicated that large and small trigeminal ganglion neurons express VGluT2 more frequently than VGluT1. Dual immunofluorescence histochemistry for VGluT1 and VGluT2 indicated that trigeminal ganglion neurons express VGluT2 more frequently than VGluT1 and that more than 80% of VGluT-expressing trigeminal ganglion neurons express VGluT1 and VGluT2. Many axon terminals in the superficial layers of the medullary dorsal horn also showed VGluT1 and VGluT2 immunoreactivities. Some of these axon terminals were confirmed to form the central core of the synaptic glomerulus. These results indicated that VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most trigeminal ganglion neurons. Copyright 2003 Wiley-Liss, Inc.

  12. Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation.

    PubMed

    Guntur, Anyonya R; Gerencser, Akos A; Le, Phuong T; DeMambro, Victoria E; Bornstein, Sheila A; Mookerjee, Shona A; Maridas, David E; Clemmons, David E; Brand, Martin D; Rosen, Clifford J

    2018-06-01

    Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

  13. One-step synthesis of water-dispersible ultra-small Fe3O4 nanoparticles as contrast agents for T1 and T2 magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Wang, Guannan; Zhang, Xuanjun; Skallberg, Andreas; Liu, Yaxu; Hu, Zhangjun; Mei, Xifan; Uvdal, Kajsa

    2014-02-01

    Uniform, highly water-dispersible and ultra-small Fe3O4 nanoparticles were synthesized via a modified one-step coprecipitation approach. The prepared Fe3O4 nanoparticles not only show good magnetic properties, long-term stability in a biological environment, but also exhibit good biocompatibility in cell viability and hemolysis assay. Due to the ultra-small sized and highly water-dispersibility, they exhibit excellent relaxivity properties, the 1.7 nm sized Fe3O4 nanoparticles reveal a low r2/r1 ratio of 2.03 (r1 = 8.20 mM-1 s-1, r2 = 16.67 mM-1 s-1) and the 2.2 nm sized Fe3O4 nanoparticles also appear to have a low r2/r1 ratio of 4.65 (r1 = 6.15 mM-1 s-1, r2 = 28.62 mM-1 s-1). This demonstrates that the proposed ultra-small Fe3O4 nanoparticles have great potential as a new type of T1 magnetic resonance imaging contrast agents. Especially, the 2.2 nm sized Fe3O4 nanoparticles, have a competitive r1 value and r2 value compared to commercial contrasting agents such as Gd-DTPA (r1 = 4.8 mM-1 s -1), and SHU-555C (r2 = 69 mM-1 s-1). In vitro and in vivo imaging experiments, show that the 2.2 nm sized Fe3O4 nanoparticles exhibit great contrast enhancement, long-term circulation, and low toxicity, which enable these ultra-small sized Fe3O4 nanoparticles to be promising as T1 and T2 dual contrast agents in clinical settings.Uniform, highly water-dispersible and ultra-small Fe3O4 nanoparticles were synthesized via a modified one-step coprecipitation approach. The prepared Fe3O4 nanoparticles not only show good magnetic properties, long-term stability in a biological environment, but also exhibit good biocompatibility in cell viability and hemolysis assay. Due to the ultra-small sized and highly water-dispersibility, they exhibit excellent relaxivity properties, the 1.7 nm sized Fe3O4 nanoparticles reveal a low r2/r1 ratio of 2.03 (r1 = 8.20 mM-1 s-1, r2 = 16.67 mM-1 s-1) and the 2.2 nm sized Fe3O4 nanoparticles also appear to have a low r2/r1 ratio of 4.65 (r1 = 6.15 mM-1 s

  14. Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

    PubMed

    Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

    2014-07-01

    Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is

  15. Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoyong; Zhou, Zijian; Wang, Zhiyong; Xue, Yunxin; Zeng, Yun; Gao, Jinhao; Zhu, Lei; Zhang, Xianzhong; Liu, Gang; Chen, Xiaoyuan

    2013-08-01

    This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02797j

  16. SU-G-JeP2-12: Quantification of 3D Geometric Distortion for 1.5T and 3T MRI Scanners Used for Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stowe, M; Gupta, N; Raterman, B

    Purpose: To quantify the magnitude of geometric distortion for MRI scanners and provide recommendations for MRI imaging for radiation therapy Methods: A novel phantom, QUASAR MRID3D [Modus Medical Devices Inc.], was scanned to evaluate the level of 3D geometric distortion present in five MRI scanners used for radiation therapy in our department. The phantom was scanned using the body coil with 1mm image slice thickness to acquire 3D images of the phantom body. The phantom was aligned to its geometric center for each scan, and the field of view was set to visualize the entire phantom. The dependence of distortionmore » magnitude with distance from imaging isocenter and with magnetic field strength (1.5T and 3T) was investigated. Additionally, the characteristics of distortion for Siemens and GE machines were compared. The image distortion for each scanner was quantified in terms of mean, standard deviation (STD), maximum distortion, and skewness. Results: The 3T and 1.5T scans show a similar absolute distortion with a mean of 1.38mm (0.33mm STD) for 3T and 1.39mm (0.34mm STD) for 1.5T for a 100mm radius distance from isocenter. Some machines can have a distortion larger than 10mm at a distance of 200mm from the isocenter. The distortions are presented with plots of the x, y, and z directional components. Conclusion: The results indicate that quantification of MRI image distortion is crucial in radiation oncology for target and organ delineation and treatment planning. The magnitude of geometric distortion determines the margin needed for target contouring which is usually neglected in treatment planning process, especially for SRS/SBRT treatments. Understanding the 3D distribution of the MRI image distortion will improve the accuracy of target delineation and, hence, treatment efficacy. MRI imaging with proper patient alignment to the isocenter is vital to reducing the effects of MRI distortion in treatment planning.« less

  17. States of phage T3/T7 capsids: buoyant density centrifugation and cryo-EM.

    PubMed

    Serwer, Philip; Wright, Elena T; Demeler, Borries; Jiang, Wen

    2018-04-01

    Mature double-stranded DNA bacteriophages have capsids with symmetrical shells that typically resist disruption, as they must to survive in the wild. However, flexibility and associated dynamism assist function. We describe biochemistry-oriented procedures used to find previously obscure flexibility for capsids of the related phages, T3 and T7. The primary procedures are hydration-based buoyant density ultracentrifugation and purified particle-based cryo-electron microscopy (cryo-EM). We review the buoyant density centrifugation in detail. The mature, stable T3/T7 capsid is a shell flexibility-derived conversion product of an initially assembled procapsid (capsid I). During DNA packaging, capsid I expands and loses a scaffolding protein to form capsid II. The following are observations made with capsid II. (1) The in vivo DNA packaging of wild type T3 generates capsid II that has a slight (1.4%), cryo-EM-detected hyper-expansion relative to the mature phage capsid. (2) DNA packaging in some altered conditions generates more extensive hyper-expansion of capsid II, initially detected by hydration-based preparative buoyant density centrifugation in Nycodenz density gradients. (3) Capsid contraction sometimes occurs, e.g., during quantized leakage of DNA from mature T3 capsids without a tail.

  18. Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material.

    PubMed Central

    Nagai, H; Kuroda, A; Morioka, Y

    1986-01-01

    Eight autopsy cases of pancreatic cancer (duct cell adenocarcinoma) with T1 and T2 primary tumors were studied histologically to examine the exact extent of lymphatic and local spread. Six of them had microscopic metastasis in grossly negative lymph nodes near the primary tumor. In addition, four of them had a few metastatic nodes in the para-aortic region. In cases with lymphatic metastases, the extent of cancer infiltration within lymphatic vessels, nerves, and/or connective tissues was almost the same as that of lymph node metastasis. Major vascular involvement was found in four cases. There was no case in which multicentricity or marked intraductal spread of cancer cells was observed in the pancreas. It has been suggested that most of T1 and T2 pancreatic cancers have a fairly widespread microscopic extension, although extremely small T1 cancers have a very limited extension. Images FIG. 2. FIGS. 4a-c. FIGS. 5a-c. PMID:3015059

  19. ZnT-1 enhances the activity and surface expression of T-type calcium channels through activation of Ras-ERK signaling.

    PubMed

    Mor, Merav; Beharier, Ofer; Levy, Shiri; Kahn, Joy; Dror, Shani; Blumenthal, Daniel; Gheber, Levi A; Peretz, Asher; Katz, Amos; Moran, Arie; Etzion, Yoram

    2012-07-15

    Zinc transporter-1 (ZnT-1) is a putative zinc transporter that confers cellular resistance from zinc toxicity. In addition, ZnT-1 has important regulatory functions, including inhibition of L-type calcium channels and activation of Raf-1 kinase. Here we studied the effects of ZnT-1 on the expression and function of T-type calcium channels. In Xenopus oocytes expressing voltage-gated calcium channel (CaV) 3.1 or CaV3.2, ZnT-1 enhanced the low-threshold calcium currents (I(caT)) to 182 ± 15 and 167.95 ± 9.27% of control, respectively (P < 0.005 for both channels). As expected, ZnT-1 also enhanced ERK phosphorylation. Coexpression of ZnT-1 and nonactive Raf-1 blocked the ZnT-1-mediated ERK phosphorylation and abolished the ZnT-1-induced augmentation of I(caT). In mammalian cells (Chinese hamster ovary), coexpression of CaV3.1 and ZnT-1 increased the I(caT) to 166.37 ± 6.37% compared with cells expressing CaV3.1 alone (P < 0.01). Interestingly, surface expression measurements using biotinylation or total internal reflection fluorescence microscopy indicated marked ZnT-1-induced enhancement of CaV3.1 surface expression. The MEK inhibitor PD-98059 abolished the ZnT-1-induced augmentation of surface expression of CaV3.1. In cultured murine cardiomyocytes (HL-1 cells), transient exposure to zinc, leading to enhanced ZnT-1 expression, also enhanced the surface expression of endogenous CaV3.1 channels. Consistently, in these cells, endothelin-1, a potent activator of Ras-ERK signaling, enhanced the surface expression of CaV3.1 channels in a PD-98059-sensitive manner. Our findings indicate that ZnT-1 enhances the activity of CaV3.1 and CaV3.2 through activation of Ras-ERK signaling. The augmentation of CaV3.1 currents by Ras-ERK activation is associated with enhanced trafficking of the channel to the plasma membrane.

  20. Magnetic resonance transverse relaxation time T2 of knee cartilage in osteoarthritis at 3-T: a cross-sectional multicentre, multivendor reproducibility study.

    PubMed

    Balamoody, Sharon; Williams, Tomos G; Wolstenholme, Chris; Waterton, John C; Bowes, Michael; Hodgson, Richard; Zhao, Sha; Scott, Marietta; Taylor, Chris J; Hutchinson, Charles E

    2013-04-01

    The transverse relaxation time (T2) in MR imaging has been identified as a potential biomarker of hyaline cartilage pathology. This study investigates whether MR assessments of T2 are comparable between 3-T scanners from three different vendors. Twelve subjects with symptoms of knee osteoarthritis and one or more risk factors had their knee scanned on each of the three vendors' scanners located in three sites in the U.K. MR data acquisition was based on the United States National Institutes of Health Osteoarthritis Initiative protocol. Measures of cartilage T2 and R2 (inverse of T2) were computed for precision error assessment. Intrascanner reproducibility was also assessed with a phantom (all three scanners) and a cohort of 5 subjects (one scanner only). Whole-organ magnetic resonance (WORM) semiquantitative cartilage scores ranged from minimal to advanced degradation. Intrascanner R2 root-mean-square coefficients of variation (RMSCOV) were low, within the range 2.6 to 6.3% for femoral and tibial regions. For one scanner pair, mean T2 differences ranged from -1.2 to 2.8 ms, with no significant difference observed for the medial tibia and patella regions (p < 0.05). T2 values from the third scanner were systematically lower, producing interscanner mean T2 differences within the range 5.4 to 10.0 ms. Significant interscanner cartilage T2 differences were found and should be accounted for before data from scanners of different vendors are compared.

  1. Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2

    PubMed Central

    Crouthamel, Matthew H.; Lau, Wei Ling; Leaf, Elizabeth M.; Chavkin, Nick; Wallingford, Mary C.; Peterson, Danielle F.; Li, Xianwu; Liu, Yonggang; Chin, Michael T.; Levi, Moshe; Giachelli, Cecilia M.

    2014-01-01

    Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells. PMID:23968976

  2. [The effect of Foxc2 overexpression on the osteogenic properties of C3H10T1/2 cells].

    PubMed

    Wang, Min-Jiao; Si, Jia-Wen; Li, Hong-Liang; Ouyang, Ning-Juan; Shen, Guo-Fang

    2016-08-01

    To investigate the effect of Foxc2 overexpression on osteogenic and adipogenic differentiation of C3H10T1/2 cells. C3H10T1/2 cells were transfected with plenti-Foxc2 and selected with puromycin for stable clones. The expression of Foxc2 was determined by real-time PCR and Western blot. Cell proliferation was detected by CCK-8 kit. Cell cycle and apoptosis were detected by flow cytometry. The level of osteogenic biomarkers Runx2, OPN, OCN and adipogenic biomarker PPARγ were quantified by real-time PCR and Western blot. Alkaline phosphatase (ALP) staining and oil red staining were conducted to evaluate the effect of Foxc2 overexpression on osteogenic and adipogenic differentiation. Statistical analysis was performed using SPSS 17.0 software package. C3H10T1/2-Foxc2 cell line was successfully constructed and verified by direct sequencing and Foxc2 overexpression in vitro. Cell proliferation was reduced and cell cycle was blocked in G1/G0 phase. Enhanced ALP staining and reduced oil red staining were observed in C3H10T1/2-Foxc2 cells as compared with the control. Foxc2 overexpression up-regulated Runx2, OPN, OCN during osteogenic differentiation and down-regulated PPARγduring adipogenic differentiation. C3H10T1/2 cell line stably expressing Foxc2 gene was successfully established, cell proliferation was reduced, osteogenesis biomarkers were up-regulated during the osteogenesis by overexpression Foxc2, PPARγwas down-regulated during adipogenesis.

  3. Functional characterization of the heterodimeric sweet taste receptor T1R2 and T1R3 from a New World monkey species (squirrel monkey) and its response to sweet-tasting proteins

    PubMed Central

    Liu, Bo; Ha, Matthew; Meng, Xuan-Yu; Khaleduzzaman, Mohammed; Zhang, Zhe; Li, Xia; Cui, Meng

    2012-01-01

    The family C G protein-coupled receptor (GPCR) T1R2 and T1R3 heterodimer functions as a broadly acting sweet taste receptor. Perception of sweet taste is a species-dependent physiological process. It has been widely reported that New World monkeys and rodents can not perceive some of the artificial sweeteners and sweet-tasting proteins that can be perceived by humans, apes, and Old World monkeys. Until now, only the sweet receptors of humans, mice and rats have been functionally characterized. Here we report characterization of the sweet taste receptor (T1R2/T1R3) from a species of New World squirrel monkey. Our results show that the heterodimeric receptor of squirrel monkey does not respond to artificial sweeteners aspartame, neotame, cyclamate, saccharin and sweet-tasting protein monellin, but surprisingly, it does respond to thaumatin at high concentrations (>18 μM). This is the first report that New World monkey species can perceive some specific sweet-tasting proteins. Furthermore, the receptor responses to the sweeteners cannot be inhibited by the sweet inhibitor lactisole. We compared the response differences of the squirrel monkey and human receptors and found that the residues in T1R2 determine species-dependent sweet taste toward saccharin, while the residues in either T1R2 or T1R3 are responsible for the sweet taste difference between humans and squirrel monkeys toward monellin. Molecular models indicated that electrostatic properties of the receptors probably mediate the species-dependent response to sweet-tasting proteins. PMID:23000410

  4. Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain.

    PubMed

    Nakamura, Kouichi; Hioki, Hiroyuki; Fujiyama, Fumino; Kaneko, Takeshi

    2005-11-21

    Vesicular glutamate transporter 1 (VGluT1) and VGluT2 accumulate neurotransmitter glutamate into synaptic vesicles at presynaptic terminals, and their antibodies are thus considered to be a good marker for glutamatergic axon terminals. In the present study, we investigated the postnatal development and maturation of glutamatergic neuronal systems by single- and double-immunolabelings for VGluT1 and VGluT2 in mouse forebrain including the telencephalon and diencephalon. VGluT2 immunoreactivity was widely distributed in the forebrain, particularly in the diencephalon, from postnatal day 0 (P0) to adulthood, suggesting relatively early maturation of VGluT2-loaded glutamatergic axons. In contrast, VGluT1 immunoreactivity was intense only in the limbic regions at P0, and drastically increased in the other telencephalic and diencephalic regions during three postnatal weeks. Interestingly, VGluT1 immunoreactivity was frequently colocalized with VGluT2 immunoreactivity at single axon terminal-like profiles in layer IV of the primary somatosensory area from P5 to P10 and in the ventral posteromedial thalamic nucleus from P0 to P14. This was in sharp contrast to the finding that almost no colocalization was found in glomeruli of the olfactory bulb, patchy regions of the caudate-putamen, and the ventral posterolateral thalamic nucleus, where moderate to intense immunoreactivities for VGluT1 and VGluT2 were intermingled with each other in neuropil during postnatal development. The present results indicate that VGluT2-loaded glutamatergic axons maturate earlier than VGluT1-laden axons in the mouse telencephalic and diencephalic regions, and suggest that VGluT1 plays a transient developmental role in some glutamatergic systems that mainly use VGluT2 in the adulthood. (c) 2005 Wiley-Liss, Inc.

  5. Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues.

    PubMed

    Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

    2014-06-01

    In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3',5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. © 2014 The authors.

  6. The diagnostic performance of non-contrast 3-Tesla magnetic resonance imaging (3-T MRI) versus 1.5-Tesla magnetic resonance arthrography (1.5-T MRA) in femoro-acetabular impingement.

    PubMed

    Crespo-Rodríguez, Ana M; De Lucas-Villarrubia, Jose C; Pastrana-Ledesma, Miguel; Hualde-Juvera, Ana; Méndez-Alonso, Santiago; Padron, Mario

    2017-03-01

    The aim of this study was to evaluate the diagnostic accuracy of 3-T non-contrast MRI versus 1.5-T MRA for assessing labrum and articular cartilage lesions in patients with clinical suspicion of femoro-acetabular impingement (FAI). Fifty patients (thirty men and twenty women, mean age 42.5 years) underwent 1.5-T MRA, 3-T MRI and arthroscopy on the same hip. An optimized high-resolution proton density spin echo pulse sequence was included in the 3-T non-contrast MRI protocol. The 3-T non-contrast MRI identified forty-two of the forty-three arthroscopically proven tears at the labral-chondral transitional zone (sensitivity, 97.7%; specificity, 100%; positive predictive value (PPV), 100%; negative predictive value (NPV), 87.5%; accuracy 98%). With 1.5-T MRA, forty-four tears were diagnosed. However, there was one false positive (sensitivity, 100%; specificity, 85.7%; PPV, 97.7%; NPV, 100%; accuracy 98%). Agreement between arthroscopy and MRI, whether 3-T non-contrast MRI or 1.5-T MRA, as to the degree of chondral lesion in the acetabulum was reached in half of the patients and in the femur in 76% of patients. Non-invasive assessment of the hip is possible with 3-T MR magnet. 3-T non-contrast MRI could replace MRA as the workhorse technique for assessing hip internal damage. MRA would then be reserved for young adults with a strong clinical suspicion of FAI but normal findings on 3-T non-contrast MRI. When compared with 1.5-T MRA, optimized sequences with 3-T non-contrast MRI help in detecting normal variants and in diagnosing articular cartilage lesions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Improved l1-SPIRiT using 3D walsh transform-based sparsity basis.

    PubMed

    Feng, Zhen; Liu, Feng; Jiang, Mingfeng; Crozier, Stuart; Guo, He; Wang, Yuxin

    2014-09-01

    l1-SPIRiT is a fast magnetic resonance imaging (MRI) method which combines parallel imaging (PI) with compressed sensing (CS) by performing a joint l1-norm and l2-norm optimization procedure. The original l1-SPIRiT method uses two-dimensional (2D) Wavelet transform to exploit the intra-coil data redundancies and a joint sparsity model to exploit the inter-coil data redundancies. In this work, we propose to stack all the coil images into a three-dimensional (3D) matrix, and then a novel 3D Walsh transform-based sparsity basis is applied to simultaneously reduce the intra-coil and inter-coil data redundancies. Both the 2D Wavelet transform-based and the proposed 3D Walsh transform-based sparsity bases were investigated in the l1-SPIRiT method. The experimental results show that the proposed 3D Walsh transform-based l1-SPIRiT method outperformed the original l1-SPIRiT in terms of image quality and computational efficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Efficient CRISPR/Cas9-mediated gene editing in Arabidopsis thaliana and inheritance of modified genes in the T2 and T3 generations.

    PubMed

    Jiang, WenZhi; Yang, Bing; Weeks, Donald P

    2014-01-01

    The newly developed CRISPR/Cas9 system for targeted gene knockout or editing has recently been shown to function in plants in both transient expression systems as well as in primary T1 transgenic plants. However, stable transmission of genes modified by the Cas9/single guide RNA (sgRNA) system to the T2 generation and beyond has not been demonstrated. Here we provide extensive data demonstrating the efficiency of Cas9/sgRNA in causing modification of a chromosomally integrated target reporter gene during early development of transgenic Arabidopsis plants and inheritance of the modified gene in T2 and T3 progeny. Efficient conversion of a nonfunctional, out-of-frame GFP gene to a functional GFP gene was confirmed in T1 plants by the observation of green fluorescent signals in leaf tissues as well as the presence of mutagenized DNA sequences at the sgRNA target site within the GFP gene. All GFP-positive T1 transgenic plants and nearly all GFP-negative plants examined contained mutagenized GFP genes. Analyses of 42 individual T2 generation plants derived from 6 different T1 progenitor plants showed that 50% of T2 plants inherited a single T-DNA insert. The efficiency of the Cas9/sgRNA system and stable inheritance of edited genes point to the promise of this system for facile editing of plant genes.

  9. A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells.

    PubMed

    Mao, Yujia; Yin, Shanshan; Zhang, Jianmin; Hu, Yu; Huang, Bo; Cui, Lianxian; Kang, Ning; He, Wei

    2016-03-01

    Interleukin 4 (IL-4) has a variety of immune functions, including helper T-cell (Th-cell) differentiation and innate immune-response processes. However, the impact of IL-4 on gamma delta (γδ) T cells remains unclear. In this study, we investigate the effects of IL-4 on the activation and proliferation of γδ T cells and the balance between variable delta 1 (Vδ1) and Vδ2 T cells in humans. The results show that IL-4 inhibits the activation of γδ T cells in the presence of γδ T-cell receptor (TCR) stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated γδ T cells and increased the levels of Vδ1 T cells, which in turn inhibited Vδ2 T-cell growth via significant IL-10 secretion. Vδ1 T cells secreted significantly less interferon gamma (IFNγ) and more IL-10 relative to Vδ2. Furthermore, Vδ1 T cells showed relatively low levels of Natural Killer Group 2D (NKG2D) expression in the presence of IL-4, suggesting that Vδ1 T cells weaken the γδ T cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in γδ T cell-mediated anti-tumor immunity.

  10. Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop*

    PubMed Central

    Monteil, Arnaud; Chausson, Patrick; Boutourlinsky, Katia; Mezghrani, Alexandre; Huc-Brandt, Sylvaine; Blesneac, Iulia; Bidaud, Isabelle; Lemmers, Céline; Leresche, Nathalie; Lambert, Régis C.; Lory, Philippe

    2015-01-01

    Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser423–Pro542) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. PMID:25931121

  11. Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-α secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes

    PubMed Central

    Rui, Yehua; Tong, Lingxia; Cheng, Jinbo; Wang, Guiping; Qin, Liqiang; Wan, Zhongxiao

    2017-01-01

    ABSTRACT Background: Rosmarinic acid (RA) is a natural phenol carboxylic acid with many promising biological effects. It may be a suitable candidate for improving obesity-related adipose tissue dysfunction. Objective: We aimed to investigate the therapeutic use of RA as an anti-obesity agent by measuring its effects on adipogenesis, lipolysis, and messenger RNA (mRNA) expression of major adipokines in 3T3-L1 adipocytes; and its effects on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) secretion in macrophages and inflammatory mediators in 3T3-L1 adipocytes incubated with macrophage-conditioned medium (MCM). Methods: 3T3-L1 preadipocytes were used to explore how RA affects adipogenesis, as well as the involvement of phosphorylated extracellular signal-regulated kinase-1/2 (p-ERK1/2) and mothers against decapentaplegic homolog 3 (p-Smad3). 3T3-L1 preadipocytes were also differentiated into mature adipocytes to explore how RA affects basal and isoproterenol- and forskolin-stimulated lipolysis; and how RA affects key adipokines’ mRNA expression. RAW 264.7 macrophages were stimulated with LPS in the absence or presence of RA to explore RA’s effects on TNF-α secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA’s effects on interleukin-6 (IL-6), IL-1β, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression. Results: During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein-α, and activated p-ERK1/2 and p-Smad3; inhibition of adipogenesis by RA was partially restored following treatment with p-ERK1/2 and p-Smad3 inhibitors. In mature adipocytes, RA inhibited basal lipolysis; phosphodiesterase-3 inhibitor reversed this. RA also inhibited isoproterenol- and forskolin-stimulated glycerol and free fatty acid release, and the phosphorylation of hormone-sensitive lipase and perilipin. RA had no effects on leptin

  12. 26 CFR 1.860G-2T - Other rules (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Other rules (temporary). 1.860G-2T Section 1.860G-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Real Estate Investment Trusts § 1.860G-2T Other rules (temporary). (a...

  13. 26 CFR 1.860G-2T - Other rules (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Other rules (temporary). 1.860G-2T Section 1.860G-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Real Estate Investment Trusts § 1.860G-2T Other rules (temporary). (a...

  14. Challenges of T3 and T4 Translational Research

    ERIC Educational Resources Information Center

    Vukotich, Charles J., Jr.

    2016-01-01

    Translational research is a new and important way of thinking about research. It is a major priority of the National Institutes of Health (NIH) in the United States. NIH has created the Clinical and Translational Science Awards to promote this priority. NIH has defined T1 and T2 phases of translational research in the medical field, in order to…

  15. KM3NeT

    NASA Astrophysics Data System (ADS)

    de Jong, M.

    2015-07-01

    KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure has started. The prospects of the different phases of the implementation of KM3NeT are summarised.

  16. CO2-assisted fabrication of novel heterostructures of h-MoO3/1T-MoS2 for enhanced photoelectrocatalytic performance

    NASA Astrophysics Data System (ADS)

    Zhu, Chuanhui; Xu, Qun; Liu, Wei; Ren, Yumei

    2017-12-01

    Combining the peculiar properties of different ingredients in one ultimate material is an efficient route to achieve the desired functional materials. Compared to 2H-MoS2, 1T-MoS2 nanosheets display the perfect performance of hydrogen evolution reaction (HER) because of the excellent electronic conductivity. However, how to further realize HER in the visual and near-infrared (NIR) region is a great challenge. Herein, we develop an efficient method to locally pattern h-MoO3 on the ultrathin metallic 1T-MoS2 nanosheets and obtain the novel heterostructures of h-MoO3/1T-MoS2. The enhanced photoelectrochemical performance of the as-prepared heterostructures has been demonstrated. Our study indicates it is originated from the synergistic effect between h-MoO3 and 1T-MoS2, i.e., the strong optical absorption of h-MoO3 in the visible and NIR region, the excellent electronic conductivity of 1T-MoS2 and as well as the efficient separation of the photo-induced carriers from the heterostructures.

  17. Aberrant activity of NKL homeobox gene NKX3-2 in a T-ALL subset

    PubMed Central

    Meyer, Corinna; Kaufmann, Maren; Zaborski, Margarete; MacLeod, Roderick A. F.; Drexler, Hans G.

    2018-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1. Here, we describe a novel member of the NKL homeobox gene subclass, NKX3-2 (BAPX1), which is aberrantly activated in 18% of pediatric T-ALL patients analyzed while being normally expressed in developing spleen. Identification of NKX3-2 expression in T-ALL cell line CCRF-CEM qualified these cells to model its deregulation and function in a leukemic context. Genomic and chromosomal analyses demonstrated normal configuration of the NKX3-2 locus at chromosome 4p15, thus excluding cytogenetic dysregulation. Comparative expression profiling analysis of NKX3-2 patient data revealed deregulated activity of BMP- and MAPK-signalling. These candidate pathways were experimentally confirmed to mediate aberrant NKX3-2 expression. We also show that homeobox gene SIX6, plus MIR17HG and GATA3 are downstream targets of NKX3-2 and plausibly contribute to the pathogenesis of this malignancy by suppressing T-cell differentiation. Finally, NKL homeobox gene NKX2-5 was activated by NKX3-2 in CCRF-CEM and by FOXG1 in PEER, representing mutually inhibitory activators of this translocated oncogene. Together, our findings reveal a novel oncogenic NKL homeobox gene subclass member which is aberrantly expressed in a large subset of T-ALL patients and participates in a deregulated gene network likely to arise in developing spleen. PMID:29746601

  18. Aberrant activity of NKL homeobox gene NKX3-2 in a T-ALL subset.

    PubMed

    Nagel, Stefan; Meyer, Corinna; Kaufmann, Maren; Zaborski, Margarete; MacLeod, Roderick A F; Drexler, Hans G

    2018-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1. Here, we describe a novel member of the NKL homeobox gene subclass, NKX3-2 (BAPX1), which is aberrantly activated in 18% of pediatric T-ALL patients analyzed while being normally expressed in developing spleen. Identification of NKX3-2 expression in T-ALL cell line CCRF-CEM qualified these cells to model its deregulation and function in a leukemic context. Genomic and chromosomal analyses demonstrated normal configuration of the NKX3-2 locus at chromosome 4p15, thus excluding cytogenetic dysregulation. Comparative expression profiling analysis of NKX3-2 patient data revealed deregulated activity of BMP- and MAPK-signalling. These candidate pathways were experimentally confirmed to mediate aberrant NKX3-2 expression. We also show that homeobox gene SIX6, plus MIR17HG and GATA3 are downstream targets of NKX3-2 and plausibly contribute to the pathogenesis of this malignancy by suppressing T-cell differentiation. Finally, NKL homeobox gene NKX2-5 was activated by NKX3-2 in CCRF-CEM and by FOXG1 in PEER, representing mutually inhibitory activators of this translocated oncogene. Together, our findings reveal a novel oncogenic NKL homeobox gene subclass member which is aberrantly expressed in a large subset of T-ALL patients and participates in a deregulated gene network likely to arise in developing spleen.

  19. [A comparison between 3.0 T MRI and histopathology for preoperative T staging of potentially resectable esophageal cancer].

    PubMed

    Wang, Z Q; Zhang, F G; Guo, J; Zhang, H K; Qin, J J; Zhao, Y; Ding, Z D; Zhang, Z X; Zhang, J B; Yuan, J H; Li, H L; Qu, J R

    2017-03-21

    Objective: To explore the value of 3.0 T MRI using multiple sequences (star VIBE+ BLADE) in evaluating the preoperative T staging for potentially resectable esophageal cancer (EC). Methods: Between April 2015 and March 2016, a total of 66 consecutive patients with endoscopically proven resectable EC underwent 3.0T MRI in the Affiliated Cancer Hospital of Zhengzhou University.Two independent readers were assigned a T staging on MRI according to the 7th edition of UICC-AJCC TNM Classification, the results of preoperative T staging were compared and analyzed with post-operative pathologic confirmation. Results: The MRI T staging of two readers were highly consistent with histopathological findings, and the sensitivity, specificity and accuracy of preoperative T staging MR imaging were also very high. Conclusion: 3.0 T MRI using multiple sequences is with high accuracy for patients of potentially resectable EC in T staging. The staging accuracy of T1, T2 and T3 is better than that of T4a. 3.0T MRI using multiple sequences could be used as a noninvasive imaging method for pre-operative T staging of EC.

  20. Isoflavone Malonyltransferases GmIMaT1 and GmIMaT3 Differently Modify Isoflavone Glucosides in Soybean (Glycine max) under Various Stresses

    PubMed Central

    Ahmad, Muhammad Z.; Li, Penghui; Wang, Junjie; Rehman, Naveed Ur; Zhao, Jian

    2017-01-01

    Malonylated isoflavones are the major forms of isoflavonoids in soybean plants, the genes responsible for their biosyntheses are not well understood, nor their physiological functions. Here we report a new benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, deacetylvindoline 4-O-acetyltransferase (BAHD) family isoflavone glucoside malonyltransferase GmIMaT1, and GmIMaT3, which is allelic to the previously characterized GmMT7 and GmIF7MaT. Biochemical studies showed that recombinant GmIMaT1 and GmIMaT3 enzymes used malonyl-CoA and several isoflavone 7-O-glucosides as substrates. The Km values of GmIMaT1 for glycitin, genistin, and daidzin were 13.11, 23.04, and 36.28 μM, respectively, while these of GmIMaT3 were 12.94, 26.67, and 30.12 μM, respectively. Transgenic hairy roots overexpressing both GmIMaTs had increased levels of malonyldaidzin and malonylgenistin, and contents of daidzin and glycitin increased only in GmIMaT1-overexpression lines. The increased daidzein and genistein contents were detected only in GmIMaT3-overexpression lines. Knockdown of GmIMaT1 and GmIMaT3 reduced malonyldaidzin and malonylgenistin contents, and affected other isoflavonoids differently. GmIMaT1 is primarily localized to the endoplasmic reticulum while GmIMaT3 is primarily in the cytosol. By examining their transcript changes corresponding to the altered isoflavone metabolic profiles under various environmental and hormonal stresses, we probed the possible functions of GmIMaTs. Two GmIMaTs displayed distinct tissue expression patterns and respond differently to various factors in modifying isoflavone 7-O-glucosides under various stresses. PMID:28559900

  1. Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of the Short T2 Components in White Matter of the Brain Using a Clinical 3T Scanner

    PubMed Central

    Du, Jiang; Ma, Guolin; Li, Shihong; Carl, Michael; Szeverenyi, Nikolaus M; VandenBerg, Scott; Corey-Bloom, Jody; Bydder, Graeme M

    2014-01-01

    White matter of the brain contains a majority of long T2 components as well as a minority of short T2 components. These are not detectable using clinical magnetic resonance imaging (MRI) sequences with conventional echo times (TEs). In this study we used ultrashort echo time (UTE) sequences to investigate the ultrashort T2 components in white matter of the brain and quantify their T2*s and relative proton densities (RPDs) (relative to water with a proton density of 100%) using a clinical whole body 3T scanner. An adiabatic inversion recovery prepared dual echo UTE (IR-dUTE) sequence was used for morphological imaging of the ultrashort T2 components in white matter. IR-dUTE acquisitions at a constant TR of 1000 ms and a series of TIs were performed to determine the optimal TI which corresponded to the minimum signal to noise ratio (SNR) in white matter of the brain on the second echo image. T2*s of the ultrashort T2 components were quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of TEs. RPD was quantified by comparing IR-dUTE signal of the ultrashort T2 components with that of a rubber phantom. Nine healthy volunteers were studied. The IR-dUTE sequence provided excellent image contrast for the ultrashort T2 components in white matter of the brain with a mean signal to noise ratio of 18.7 ± 3.7 and a contrast to noise ratio of 14.6 ± 2.4 between the ultrashort T2 white matter and gray matter in a 4.4 min scan time with a nominal voxel size of 1.25×1.25×5.0 mm3. On average a T2* value of 0.42 ± 0.08 ms and a RPD of 4.05 ± 0.88% were demonstrated for the ultrashort T2 components in white matter of the brain of healthy volunteers at 3T. PMID:24188809

  2. Structural, vibrational, and electrical properties of 1 T -TiT e2 under hydrostatic pressure: Experiments and theory

    NASA Astrophysics Data System (ADS)

    Rajaji, V.; Dutta, Utpal; Sreeparvathy, P. C.; Sarma, Saurav Ch.; Sorb, Y. A.; Joseph, B.; Sahoo, Subodha; Peter, Sebastian C.; Kanchana, V.; Narayana, Chandrabhas

    2018-02-01

    We report the structural, vibrational, and electrical transport properties up to ˜16 GPa of 1 T -TiT e2 , a prominent layered 2D system. We clearly show signatures of two isostructural transitions at ˜2 GPa and ˜4 GPa obtained from the minima in c /a ratio concomitant with the phonon linewidth anomalies of Eg and A1 g modes around the same pressures, providing a strong indication of unusual electron-phonon coupling associated with these transitions. Resistance measurements present nonlinear behavior over similar pressure ranges shedding light on the electronic origin of these pressure-driven isostructural transitions. These multiple indirect signatures of an electronic transition at ˜2 GPa and ˜4 GPa are discussed in connection with the recent theoretical proposal for 1 T -TiT e2 and also the possibility of an electronic topological transition from our electronic Fermi surface calculations. Between 4 GPa and ˜8 GPa , the c /a ratio shows a plateau suggesting a transformation from an anisotropic 2D layer to a quasi-3D crystal network. First-principles calculations suggest that the 2D to quasi-3D evolution without any structural phase transitions is mainly due to the increased interlayer Te-Te interactions (bridging) via the charge density overlap. In addition, we observed a first-order structural phase transition from the trigonal (P 3 ¯m 1 ) to monoclinic (C 2 /m ) phase at higher pressure regions. We estimate the start of this structural phase transition to be ˜8 GPa and also the coexistence of two phases [trigonal (P 3 ¯m 1 ) and monoclinic (C 2 /m )] was observed from ˜8 GPa to ˜16 GPa .

  3. One-Electron Oxidation of [M(P(t) Bu3 )2 ] (M=Pd, Pt): Isolation of Monomeric [Pd(P(t) Bu3 )2 ](+) and Redox-Promoted C-H Bond Cyclometalation.

    PubMed

    Troadec, Thibault; Tan, Sze-Yin; Wedge, Christopher J; Rourke, Jonathan P; Unwin, Patrick R; Chaplin, Adrian B

    2016-03-07

    Oxidation of zero-valent phosphine complexes [M(P(t) Bu3 )2 ] (M=Pd, Pt) has been investigated in 1,2-difluorobenzene solution using cyclic voltammetry and subsequently using the ferrocenium cation as a chemical redox agent. In the case of palladium, a mononuclear paramagnetic Pd(I) derivative was readily isolated from solution and fully characterized (EPR, X-ray crystallography). While in situ electrochemical measurements are consistent with initial one-electron oxidation, the heavier congener undergoes C-H bond cyclometalation and ultimately affords the 14 valence-electron Pt(II) complex [Pt(κ(2) PC -P(t) Bu2 CMe2 CH2 )(P(t) Bu3 )](+) with concomitant formation of [Pt(P(t) Bu3 )2 H](+) . © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  4. Bilateral cartilage T2 mapping 9 years after Mega-OATS implantation at the knee: a quantitative 3T MRI study.

    PubMed

    Jungmann, P M; Brucker, P U; Baum, T; Link, T M; Foerschner, F; Minzlaff, P; Banke, I J; Saier, T; Imhoff, A B; Rummeny, E J; Bauer, J S

    2015-12-01

    To evaluate morphological and quantitative MR findings 9 years after autograft transfer of the posterior femoral condyle (Mega-OATS) and to correlate these findings with clinical outcomes. Quantitative MR measurements were also obtained of the contralateral knee and the utility as reference standard was investigated. Both knees of 20 patients with Mega-OATS osteochondral repair at the medial femoral condyle (MFC) were studied using 3T MRI 9 years after the procedure. MR-sequences included morphological sequences and a 2D multislice multiecho (MSME) spin echo (SE) sequence for quantitative cartilage T2 mapping. Cartilage segmentation was performed at the cartilage repair site and six additional knee compartments. Semi-quantitative MR observation of cartilage repair tissue (MOCART) scores and clinical Lysholm scores were obtained. Paired t-tests and Spearman correlations were used for statistical analysis. Global T2-values were significantly higher at ipsilateral knees compared to contralateral knees (42.1 ± 3.0 ms vs 40.4 ± 2.6 ms, P = 0.018). T2-values of the Mega-OATS site correlated significantly with MOCART scores (R = -0.64, P = 0.006). The correlations between MOCART and Lysholm scores and between absolute T2-values and Lysholm scores were not significant (P > 0.05). However, higher T2 side-to-side differences at the femoral condyles correlated significantly with more severe clinical symptoms (medial, R = -0.53, P = 0.030; lateral, R = -0.51, P = 0.038). Despite long-term survival, 9 years after Mega-OATS procedures, T2-values of the grafts were increased compared to contralateral knees. Clinical scores correlated best with T2 side-to-side differences of the femoral condyles, indicating that intraindividual adjustment may be beneficial for outcome evaluation. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  5. Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko

    2010-05-28

    In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, bothmore » DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.« less

  6. The Vγ9Vδ2 T Cell Antigen Receptor and Butyrophilin-3 A1: Models of Interaction, the Possibility of Co-Evolution, and the Case of Dendritic Epidermal T Cells

    PubMed Central

    Karunakaran, Mohindar M.; Herrmann, Thomas

    2014-01-01

    Most circulating human gamma delta T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains show a Vγ9-JP (Vγ2-Jγ1.2) rearrangement and are paired with Vδ2-containing δ-chains, a dominant TCR configuration, which until recently seemed to occur in primates only. Vγ9Vδ2 T cells respond to phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. A prerequisite for PAg-induced activation is the contact of Vγ9Vδ2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will first critically review models of how BTN3 might act in PAg-mediated Vγ9Vδ2 T cell activation and then address putative co-evolution of Vγ9, Vδ2, and BTN3 genes. In those rodent and lagomorphs used as animal models, all three genes are lost but a data-base analysis showed that they emerged together with placental mammals. A strong concomitant conservation of functional Vγ9, Vδ2, and BTN3 genes in other species suggests co-evolution of these three genes. A detailed analysis was performed for the new world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a non-primate species with presumably functional Vγ9Vδ2 T cells since TCR rearrangements share features characteristic for PAg-reactive primate Vγ9Vδ2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved. Finally, we analyze the possible functional relationship between the butyrophilin-family member Skint1 and the γδ TCR-V genes used by murine dendritic epithelial T cells (DETC). Among placental mammals, we identify five rodents, the cow, a bat, and the cape golden mole as the only species concomitantly possessing potentially functional homologs of murine Vγ3, Vδ4 genes, and Skint1 gene and suggest to search for DETC like cells in these

  7. Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer's disease cortex.

    PubMed

    Sokolow, Sophie; Luu, Sanh H; Nandy, Karabi; Miller, Carol A; Vinters, Harry V; Poon, Wayne W; Gylys, Karen H

    2012-01-01

    Amyloid-beta (Aβ) is thought to play a central role in synaptic dysfunction (e.g. neurotransmitter release) and synapse loss. Glutamatergic dysfunction is involved in the pathology of Alzheimer's disease (AD) and perhaps plays a central role in age-related cognitive impairment. Yet, it is largely unknown whether Aβ accumulates in excitatory boutons. To assess the possibility that glutamatergic terminals are lost in AD patients, control and AD synaptosomes were immunolabeled for the most abundant vesicular glutamate transporters (VGluT1 and VGluT2) and quantified by flow cytometry and immunoblot methods. In post-mortem parietal cortex from aged control subjects, glutamatergic boutons are fairly abundant as approximately 40% were immunoreactive for VGluT1 (37%) and VGluT2 (39%). However, the levels of these specific markers of glutamatergic synapses were not significantly different among control and AD cases. To test the hypothesis that Aβ is associated with excitatory terminals, AD synaptosomes were double-labeled for Aβ and for VGluT1 and VGluT2, and analyzed by flow cytometry and confocal microscopy. Our study demonstrated that Aβ immunoreactivity (IR) was present in glutamatergic terminals of AD patients. Quantification of Aβ and VGluT1 in a large population of glutamatergic nerve terminals was performed by flow cytometry, showing that 42% of VGluT1 synaptosomes were immunoreactive for Aβ compared to 9% of VGluT1 synaptosomes lacking Aβ-IR. Percentage of VGluT2 synaptosomes immunoreactive for Aβ (21%) was significantly higher than VGluT2 synaptosomes lacking Aβ-IR (9%). Moreover, Aβ preferentially affects VGluT1 (42% positive) compared to VGluT2 terminals (21%). These data represent the first evidence of high levels of Aβ in excitatory boutons in AD cortex and support the hypothesis that Aβ may play a role in modulating glutamate transmission in AD terminals. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. KM3NeT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jong, M. de; Leiden Institute of Physics, Leiden University, Leiden; Collaboration: KM3NeT Collaboration

    2015-07-15

    KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure hasmore » started. The prospects of the different phases of the implementation of KM3NeT are summarised.« less

  9. T11TS immunotherapy repairs PI3K-AKT signaling in T-cells: Clues toward enhanced T-cell survival in rat glioma model.

    PubMed

    Chaudhuri, Suhnrita; Singh, Manoj K; Bhattacharya, Debanjan; Datta, Ankur; Hazra, Iman; Mondal, Somnath; Faruk Sk Md, Omar; Ronsard, Larance; Ghosh, Tushar K; Chaudhuri, Swapna

    2018-02-01

    Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats. This lead to investigations whether such T-cell activation upon T11TS therapy translates into activation of downstream PI3K/AKT signals which may be related to observed blockade of T-cell apoptosis. For the purpose, we assessed by flowcytometry and immunoblotting, expressions of PI3K, PDK1, AKT, p-AKT, and PTEN in splenic T-cells of normal, experimentally-induced glioma-bearing rats and glioma-bearing rats receiving first, second and third doses of T11TS. We also determined comparative nuclear translocation of NF-κB across groups. We found significant increases in T-cell expressions of PDK1, PI3K, and p-AKT in T11TS-treated animal groups compared to sharp downregulations in glioma. AKT levels remained unchanged across groups. PTEN levels declined sharply after T11TS immunotherapy. T11TS also caused enhanced NF-κB translocation to the T-cell nucleus compared to glioma group. Results showed heightened activation of the PI3K-AKT pathway in glioma-bearing rats following T11TS immunotherapy. These results illustrate the novel role of T11TS immunotherapy in ameliorating the PI3K pathway in T-cells in glioma-bearing animals to enhance T-cell survival, according greater defense against glioma. The study thus has far-reaching clinical outcomes. © 2017 Wiley Periodicals, Inc.

  10. Utility approach to decision-making in extended T1 and limited T2 glottic carcinoma.

    PubMed

    van Loon, Yda; Stiggelbout, Anne M; Hakkesteegt, Marieke M; Langeveld, Ton P M; de Jong, Rob J Baatenburg; Sjögren, Elisabeth V

    2017-04-01

    It is still undecided if endoscopic laser surgery or radiotherapy is the preferable treatment in extended T1 and limited T2 glottic tumors. Health utilities assessed from patients can aid in decision-making. Patients treated for extended T1 or limited T2 glottic carcinoma by laser surgery (n = 12) or radiotherapy (n = 14) assigned health utilities using a visual analog scale (VAS), time tradeoff (TTO) technique and scored their voice handicap using the Voice Handicap Index (VHI). VAS and TTO scores were slightly lower for the laser group compared to the radiotherapy group, however, not significantly so. The VHI showed a correlation with the VAS score, which was very low in both groups and can be considered (near) normal. Patients show no clear preference for the outcomes of laser surgery or radiotherapy from a quality of life (QOL) or voice handicap point of view. These data can now be incorporated into decision-making models. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 © 2016 Wiley Periodicals, Inc. Head Neck 39: 779-785, 2017. © 2017 Wiley Periodicals, Inc.

  11. In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain metabolites at 3T.

    PubMed

    Wyss, Patrik O; Bianchini, Claudio; Scheidegger, Milan; Giapitzakis, Ioannis A; Hock, Andreas; Fuchs, Alexander; Henning, Anke

    2018-08-01

    The transverse relaxation times T 2 of 17 metabolites in vivo at 3T is reported and region specific differences are addressed. An echo-time series protocol was applied to one, two, or three volumes of interest with different fraction of white and gray matter including a total number of 106 healthy volunteers and acquiring a total number of 128 spectra. The data were fitted with the 2D fitting tool ProFit2, which included individual line shape modeling for all metabolites and allowed the T 2 calculation of 28 moieties of 17 metabolites. The T 2 of 10 metabolites and their moieties have been reported for the first time. Region specific T 2 differences in white and gray matter enriched tissue occur in 16 of 17 metabolites examined including single resonance lines and coupled spin systems. The relaxation time T 2 is regions specific and has to be considered when applying tissue composition correction for internal water referencing. Magn Reson Med 80:452-461, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  12. Reproducibility of MR-Based Liver Fat Quantification Across Field Strength: Same-Day Comparison Between 1.5T and 3T in Obese Subjects

    PubMed Central

    Artz, Nathan S.; Haufe, William M.; Hooker, Catherine A.; Hamilton, Gavin; Wolfson, Tanya; Campos, Guilherme M.; Gamst, Anthony C.; Schwimmer, Jeffrey B.; Sirlin, Claude B.; Reeder, Scott B.

    2016-01-01

    Purpose To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths. Materials and Methods This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38–53 kg/m2) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths. Results 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R2 values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = −1.4 [−2.4, −0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [−0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R2 = 0.98 (m = 1.1 [1.02, 1.16], b = −1.8 [−2.8, −1.1]) at 1.5T, and R2 = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. Conclusion This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods. PMID:25620624

  13. Reproducibility of MR-based liver fat quantification across field strength: Same-day comparison between 1.5T and 3T in obese subjects.

    PubMed

    Artz, Nathan S; Haufe, William M; Hooker, Catherine A; Hamilton, Gavin; Wolfson, Tanya; Campos, Guilherme M; Gamst, Anthony C; Schwimmer, Jeffrey B; Sirlin, Claude B; Reeder, Scott B

    2015-09-01

    To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths. This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38-53 kg/m(2) ) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths. 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R(2) values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = -1.4 [-2.4, -0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [-0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R(2)  = 0.98 (m = 1.1 [1.02, 1.16], b = -1.8 [-2.8, -1.1]) at 1.5T, and R(2)  = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods. © 2015 Wiley Periodicals, Inc.

  14. Routine clinical knee MR reports: comparison of diagnostic performance at 1.5 T and 3.0 T for assessment of the articular cartilage.

    PubMed

    Mandell, Jacob C; Rhodes, Jeffrey A; Shah, Nehal; Gaviola, Glenn C; Gomoll, Andreas H; Smith, Stacy E

    2017-11-01

    Accurate assessment of knee articular cartilage is clinically important. Although 3.0 Tesla (T) MRI is reported to offer improved diagnostic performance, literature regarding the clinical impact of MRI field strength is lacking. The purpose of this study is to compare the diagnostic performance of clinical MRI reports for assessment of cartilage at 1.5 and 3.0 T in comparison to arthroscopy. This IRB-approved retrospective study consisted of 300 consecutive knees in 297 patients who had routine clinical MRI and arthroscopy. Descriptions of cartilage from MRI reports of 165 knees at 1.5 T and 135 at 3.0 T were compared with arthroscopy. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade of the arthroscopic grading were calculated for each articular surface at 1.5 and 3.0 T. Agreement between MRI and arthroscopy was calculated with the weighted-kappa statistic. Significance testing was performed utilizing the z-test after bootstrapping to obtain the standard error. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade were 61.4%, 82.7%, 62.2%, and 77.5% at 1.5 T and 61.8%, 80.6%, 59.5%, and 75.6% at 3.0 T, respectively. The weighted kappa statistic was 0.56 at 1.5 T and 0.55 at 3.0 T. There was no statistically significant difference in any of these parameters between 1.5 and 3.0 T. Factors potentially contributing to the lack of diagnostic advantage of 3.0 T MRI are discussed.

  15. T1ρ Dispersion in Articular Cartilage

    PubMed Central

    Besier, Thor F.; Pauly, John M.; Smith, R. Lane; Delp, Scott L.; Beaupre, Gary S.; Gold, Garry E.

    2015-01-01

    Objective This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? Design Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. Results Cartilage initial elastic modulus, E0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). Conclusions T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water–protein interactions, are dependent on the cartilage structure, and were correlated in this study. PMID:26069714

  16. Cell-Cell Communication Between Fibroblast and 3T3-L1 Cells Under Co-culturing in Oxidative Stress Condition Induced by H2O2.

    PubMed

    Subramaniyan, Sivakumar Allur; Kim, Sidong; Hwang, Inho

    2016-10-01

    The present study was carried out to understand the interaction between fibroblast and 3T3-L1 preadipocyte cells under H 2 O 2 -induced oxidative stress condition. H 2 O 2 (40 μM) was added in co-culture and monoculture of fibroblast and 3T3-L1 cell. The cells in the lower well were harvested for analysis and the process was carried out for both cells. The cell growth, oxidative stress markers, and antioxidant enzymes were analyzed. Additionally, the mRNA expressions of caspase-3 and caspase-7 were selected for analysis of apoptotic pathways and TNF-α and NF-κB were analyzed for inflammatory pathways. The adipogenic marker such as adiponectin and PPAR-γ and collagen synthesis markers such as LOX and BMP-1 were analyzed in the co-culture of fibroblast and 3T3-L1 cells. Cell viability and antioxidant enzymes were significantly increased in the co-culture compared to the monoculture under stress condition. The apoptotic, inflammatory, adipogenic, and collagen-synthesized markers were significantly altered in H 2 O 2 -induced co-culture of fibroblast and 3T3-L1 cells when compared with the monoculture of H 2 O 2 -induced fibroblast and 3T3-L1 cells. In addition, the confocal microscopical investigation indicated that the co-culture of H 2 O 2 -induced 3T3-L1 and fibroblast cells increases collagen type I and type III expression. From our results, we suggested that co-culture of fat cell (3T3-L1) and fibroblast cells may influence/regulate each other and made the cells able to withstand against oxidative stress and aging. It is conceivable that the same mechanism might have been occurring from cell to cell while animals are stressed by various environmental conditions.

  17. Gaining insight into the T _2^*-T2 relationship in surface NMR free-induction decay measurements

    NASA Astrophysics Data System (ADS)

    Grombacher, Denys; Auken, Esben

    2018-05-01

    One of the primary shortcomings of the surface nuclear magnetic resonance (NMR) free-induction decay (FID) measurement is the uncertainty surrounding which mechanism controls the signal's time dependence. Ideally, the FID-estimated relaxation time T_2^* that describes the signal's decay carries an intimate link to the geometry of the pore space. In this limit the parameter T_2^* is closely linked to a related parameter T2, which is more closely linked to pore-geometry. If T_2^* ˜eq {T_2} the FID can provide valuable insight into relative pore-size and can be used to make quantitative permeability estimates. However, given only FID measurements it is difficult to determine whether T_2^* is linked to pore geometry or whether it has been strongly influenced by background magnetic field inhomogeneity. If the link between an observed T_2^* and the underlying T2 could be further constrained the utility of the standard surface NMR FID measurement would be greatly improved. We hypothesize that an approach employing an updated surface NMR forward model that solves the full Bloch equations with appropriately weighted relaxation terms can be used to help constrain the T_2^*-T2 relationship. Weighting the relaxation terms requires estimating the poorly constrained parameters T2 and T1; to deal with this uncertainty we propose to conduct a parameter search involving multiple inversions that employ a suite of forward models each describing a distinct but plausible T_2^*-T2 relationship. We hypothesize that forward models given poor T2 estimates will produce poor data fits when using the complex-inversion, while forward models given reliable T2 estimates will produce satisfactory data fits. By examining the data fits produced by the suite of plausible forward models, the likely T_2^*-T2 can be constrained by identifying the range of T2 estimates that produce reliable data fits. Synthetic and field results are presented to investigate the feasibility of the proposed technique.

  18. An imaging surface plasmon resonance biosensor assay for the detection of T-2 toxin and masked T-2 toxin-3-glucoside in wheat

    USDA-ARS?s Scientific Manuscript database

    A sensitive, rapid, and reproducible imaging surface plasmon resonance (iSPR) biosensor assay was developed to detect T-2 toxin and T-2 toxin-3-glucoside (T2-G) in wheat. In this competitive assay, an amplification strategy was used after conjugating a secondary antibody (Ab2) with gold nanoparticle...

  19. Do Cartilage Repair Procedures Prevent Degenerative Meniscus Changes? Longitudinal T1ρ and Morphological Evaluation at 3.0T

    PubMed Central

    Jungmann, Pia M.; Li, Xiaojuan; Nardo, Lorenzo; Subburaj, Karupppasamy; Lin, Wilson; Ma, C. Benjamin; Majumdar, Sharmila; Link, Thomas M.

    2014-01-01

    Background Cartilage repair (CR) procedures are widely accepted for treatment of isolated cartilage defects at the knee joint. However, it is not well known whether these procedures prevent degenerative joint disease. Hypothesis/Purpose CR procedures prevent accelerated qualitative and quantitative progression of meniscus degeneration in individuals with focal cartilage defects. Study Design Cohort Study; Level of evidence 2b Methods A total of 94 subjects were studied. CR procedures were performed on 34 patients (n=16 osteochondral transplantation, n=18 microfracture); 34 controls were matched. An additional 13 patients received CR and anterior cruciate ligament (ACL) reconstruction (CR&ACL) and 13 patients received only ACL reconstruction. 3.0T MRI with T1ρ mapping and sagittal fat-saturated intermediate-weighted fast spin echo (FSE) sequences was performed to analyze menisci quantitatively and qualitatively (Whole-Organ Magnetic Resonance Imaging Score, WORMS). CR and CR&ACL patients were examined 4 months (n=34; n=13), 1 (n=21; n=8) and 2 (n=9; n=5) years post CR. Control subjects were scanned at baseline and after 1 and 2 years, ACL patients after 1 and 2 years. Results At baseline, global meniscus T1ρ values were higher in individuals with CR (14.2±0.6ms; P=0.004) and in individuals with CR&ACL (17.1±0.9ms; P<0.001) when compared to controls (12.8±0.6ms). After two years, there was a statistical difference between T1ρ at the overlying meniscus above cartilage defects (16.4±1.0ms) and T1ρ of the subgroup of control knees without cartilage defects (12.1±0.8ms; P<0.001) and a statistical trend to the CR group (13.3±1.0 ms; P=0.088). At baseline, 35% of subjects with CR showed morphological meniscus tears at the overlying meniscus; 10% of CR subjects showed an increase of WORMS meniscus score within the first year, none progressed in the second year. Control subjects with (without) cartilage defects showed meniscus tears in 30% (5%) at baseline; 38% (19

  20. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.

    PubMed

    Wauson, Eric M; Guerra, Marcy L; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M; Cobb, Melanie H

    2015-08-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that G(I) is not central to either pathway. Although glucagon-like peptide 1, an agonist for a G(s-)coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca(2+) entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective G(q) inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for G(q). Inhibition of G(12/13) by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways.

  1. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells

    PubMed Central

    Wauson, Eric M.; Guerra, Marcy L.; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M.

    2015-01-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that Gi is not central to either pathway. Although glucagon-like peptide 1, an agonist for a Gs-coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca2+ entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective Gq inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for Gq. Inhibition of G12/13 by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways. PMID:26168033

  2. Incorporation of excess wild-type and mutant tRNA(3Lys) into human immunodeficiency virus type 1.

    PubMed Central

    Huang, Y; Mak, J; Cao, Q; Li, Z; Wainberg, M A; Kleiman, L

    1994-01-01

    Human immunodeficiency virus (HIV) particles produced in COS-7 cells transfected with HIV type 1 (HIV-1) proviral DNA contain 8 molecules of tRNA(3Lys) per 2 molecules of genomic RNA and 12 molecules of tRNA1,2Lys per 2 molecules of genomic RNA. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a human tRNA3Lys gene, there is a large increase in the amount of cytoplasmic tRNA3Lys per microgram of total cellular RNA, and the tRNA3Lys content in the virus increases from 8 to 17 molecules per 2 molecules of genomic RNA. However, the total number of tRNALys molecules per 2 molecules of genomic RNA remains constant at 20; i.e., the viral tRNA1,2Lys content decreases from 12 to 3 molecules per 2 molecules of genomic RNA. All detectable tRNA3Lys is aminoacylated in the cytoplasm of infected cells and deacylated in the virus. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a mutant amber suppressor tRNA3Lys gene (in which the anticodon is changed from TTT to CTA), there is also a large increase in the relative concentration of cytoplasmic tRNA3Lys, and the tRNA3Lys content in the virus increases from 8 to 15 molecules per 2 molecules of genomic RNA, with a decrease in viral tRNA1,2Lys from 12 to 5 molecules per 2 molecules of genomic RNA. Thus, the total number of molecules of tRNALys in the virion remains at 20. The alteration of the anticodon has little effect on the viral packaging of this mutant tRNA in spite of the fact that it no longer contains the modified base mcm 5s2U at position 34, and its ability to be aminoacylated is significantly impaired compared with that of wild-type tRNA3Lys. Viral particles which have incorporated either excess wild-type tRNA3Lys or mutant suppressor tRNA3Lys show no differences in viral infectivity compared with wild-type HIV-1. Images PMID:7966556

  3. Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer’s disease cortex

    PubMed Central

    Sokolow, Sophie; Luu, Sanh H.; Nandy, Karabi; Miller, Carol A.; Vinters, Harry V.; Poon, Wayne W.; Gylys, Karen H.

    2011-01-01

    Amyloid-beta (Aβ) is thought to play a central role in synaptic dysfunction (e.g. neurotransmitter release) and synapse loss. Glutamatergic dysfunction is involved in the pathology of Alzheimer’s disease (AD) and perhaps plays a central role in age-related cognitive impairment. Yet, it is largely unknown whether Aβ accumulates in excitatory boutons. To assess the possibility that glutamatergic terminals are lost in AD patients, control and AD synaptosomes were immunolabeled for the most abundant vesicular glutamate transporters (VGluT1 and VGluT2) and quantified by flow cytometry and immunoblot methods. In post-mortem parietal cortex from aged control subjects, glutamatergic boutons are fairly abundant as approximately 40% were immunoreactive for VGluT1 (37%) and VGluT2 (39%). However, the levels of these specific markers of glutamatergic synapses were not significantly different among control and AD cases. To test the hypothesis that Aβ is associated with excitatory terminals, AD synaptosomes were double-labeled for Aβ and for VGluT1 and VGluT2, and analyzed by flow cytometry and confocal microscopy. Our study demonstrated that Aβ immunoreactivity (IR) was present in glutamatergic terminals of AD patients. Quantification of Aβ and VGluT1 in a large population of glutamatergic nerve terminals was performed by flow cytometry, showing that 42% of VGluT1 synaptosomes were immunoreactive for Aβ compared to 9% of VGluT1 synaptosomes lacking Aβ-IR. Percentage of VGluT2 synaptosomes immunoreactive for Aβ (21%) was significantly higher than VGluT2 synaptosomes lacking Aβ-IR (9%). Moreover, Aβ preferentially affects VGluT1 (42% positive) compared to VGluT2 terminals (21%). These data represent the first evidence of high levels of Aβ in excitatory boutons in AD cortex and support the hypothesis that Aβ may play a role in modulating glutamate transmission in AD terminals. PMID:21914482

  4. Dectin-1 diversifies Aspergillus fumigatus–specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation

    PubMed Central

    Hohl, Tobias M.; Collins, Nichole; Leiner, Ingrid; Gallegos, Alena; Saijo, Shinobu; Coward, Jesse W.; Iwakura, Yoichiro

    2011-01-01

    Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus–infected wild-type mice reduces IFN-γ and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-γ or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus–infected mice. Transient deletion of monocyte-derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus–specific CD4 T cells. Our findings indicate that Dectin-1–mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-γ in innate cells, thereby decreasing T-bet expression in A. fumigatus–specific CD4 T cells and enabling Th17 differentiation. PMID:21242294

  5. 26 CFR 1.469-3T - Passive activity credit (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Passive activity credit (temporary). 1.469-3T... TAX (CONTINUED) INCOME TAXES Taxable Year for Which Deductions Taken § 1.469-3T Passive activity credit (temporary). (a) Computation of passive activity credit. The taxpayer's passive activity credit...

  6. 26 CFR 1.469-3T - Passive activity credit (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Passive activity credit (temporary). 1.469-3T... TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxable Year for Which Deductions Taken § 1.469-3T Passive activity credit (temporary). (a) Computation of passive activity credit. The taxpayer's passive activity...

  7. Investigation of Regional Influence of Magic-Angle Effect on T2 in Human Articular Cartilage with Osteoarthritis at 3 T

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Rationale and Objectives The objectives of this research study were to determine the magic-angle effect on different subregions of in vivo human femoral cartilage through the quantitative assessment of the effect of static magnetic field orientation (B0) on transverse (T2) relaxation time at 3.0 T. Materials and Methods Healthy volunteers (n = 5l; mean age, 36.4 years) and clinical patients (n = 5; mean age, 64 years) with early osteoarthritis (OA) were scanned at 3.0-T magnetic resonance using an 8-channel phased-array knee coil (transmit-receive). Results The T2 maps revealed significantly greater values in ventral than in dorsal regions. When the cartilage regions were oriented at 55° to B0 (magic angle), the longest T2 values were detected in comparison with the neighboring regions oriented 90° and 180° (0°) to B0. The subregions oriented 180° (0°) to B0 showed the lowest T2 values. Conclusions The differences in T2 values of different subregions suggest that magic-angle effect needs to be considered when interpreting cartilage abnormalities in OA patients. PMID:25481517

  8. 26 CFR 1.103(n)-2T - Private activity bond defined (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...(n)-2T Section 1.103(n)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....103(n)-2T Private activity bond defined (temporary). Q-1: What is the definition of the term “private activity bond”? A-1: In general, for purposes of §§ 1.103(n)-1T through 1.103(n)-6T, the term “private...

  9. Capacitance of Ti 3C 2T x MXene in Ionic Liquid Electrolyte

    DOE PAGES

    Lin, Zifeng; Barbara, Daffos; Taberna, Pierre-Louis; ...

    2016-04-14

    Ti 3C 2T x MXene, a two-dimensional (2D) early transition metal carbide, has shown an extremely high volumetric capacitance in aqueous electrolytes, but in a narrow voltage window (less than 1.23 V). The utilization of MXene materials in ionic liquid electrolytes with a large voltage window has never been addressed. Here, we report the preparation of the Ti 3C 2T x MXene ionogel film by vacuum filtration for use as supercapacitor electrodes operating in 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMI-TFSI) neat ionic liquid electrolyte. Due to the disordered structure of the Ti 3C 2T x hydrogel film and a stable spacing after vacuummore » drying, achieved through ionic liquid electrolyte immersion of the Ti 3C 2T x hydrogel film, the Ti 3C 2T x surface became accessible to EMI + and TFSI - ions. A capacitance of 70 F g -1 together with a large voltage window of 3 V was obtained at a scan rate of 20 mV s -1 in neat EMI-TFSI electrolyte. The electrochemical signature indicates a capacitive behavior even at a high scan rate (500 mV s -1) and a high power performance. This work opens up the possibilities of using MXene materials with various ionic liquid electrolytes.« less

  10. Non-contrast T1-mapping detects acute myocardial edema with high diagnostic accuracy: a comparison to T2-weighted cardiovascular magnetic resonance

    PubMed Central

    2012-01-01

    Background T2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR. Methods We investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium. Results All patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls (1113 ± 94 ms, 1029 ± 59 ms and 944 ± 17 ms, respectively; p < 0.001). T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls (all p < 0.02). Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium (AUC = 0.58-0.89; p < 0.03). A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %. Conclusions Non-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing

  11. Synthesis and characterization of T[Ni(CN){sub 4}].2pyz with T=Fe, Ni; pyz=pyrazine: Formation of T-pyz-Ni bridges

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lemus-Santana, A.A.; Rodriguez-Hernandez, J.; Institute of Materials Science and Technology, University of Havana

    2011-08-15

    The formation of T-pyz-Ni bridges (pyz=pyrazine) in the T[Ni(CN){sub 4}].2pyz series is known for T=Mn, Zn, Cd and Co but not with T=Fe, Ni. In this contribution the existence of such bridges also for T=Fe, Ni is discussed. The obtained pillared solids, T[Ni(CN){sub 4}].2pyz, were characterized from XRD, TG, UV-Vis, IR, Raman, Moessbauer and magnetic data. Their crystal structures were refined in the orthorhombic Pmna space group from XRD powder patterns. The structural behavior of these solids on cooling down to 77 K was also studied. In the 180-200 K temperature range the occurrence of a structural transition to amore » monoclinic structure (P2{sub 1}/c space group) was observed. No temperature induced spin transition was observed for Fe[Ni(CN){sub 4}].2pyz. The iron (II) was found to be in high spin electronic state and this configuration is preserved on cooling down to 2 K. The magnetic data indicate the occurrence of a low temperature weak anti-ferromagnetic interaction between T metal centers within the T[Ni(CN){sub 4}] layer. In the paramagnetic region for Ni[Ni(CN){sub 4}].2pyz, a reversible temperature induced spin transition for the inner Ni atom was detected. - Graphical abstract: Rippled sheets structure for the pillared solids T[Ni(CN){sub 4}].2pyz. The pyrazine molecule is found forming T-pyz-Ni bridges between neighboring layers. Highlights: > Pillared 2D solids. > Inorganic-organic solids. > Assembling of molecular blocks. > From 1D and 2D building blocks to 3D solids.« less

  12. ErbB2 and EGFR are downmodulated during the differentiation of 3T3-L1 preadipocytes.

    PubMed

    Pagano, Eleonora; Calvo, Juan Carlos

    2003-10-15

    The expression of receptors belonging to the epidermal growth factor receptor subfamily has been largely studied these last years in epithelial cells mainly as involved in cell proliferation and malignant progression. Although much work has focused on the role of these growth factor receptors in the differentiation of a variety of tissues, there is little information in regards to normal stromal cells. We investigated erbB2 expression in the murine fibroblast cell line Swiss 3T3L1, which naturally or hormonally induced undergoes adipocyte differentiation. We found that the Swiss 3T3-L1 fibroblasts express erbB2, in addition to EGFR, and in a quantity comparable to or even greater than the breast cancer cell line T47D. Proliferating cells increased erbB2 and EGFR levels when reaching confluence up to 4- and 10-fold, respectively. This expression showed a significant decrease when growth-arrested cells were stimulated to differentiate with dexamethasone and isobutyl-methylxanthine. Differentiated cells presented a decreased expression of both erbB2 and EGFR regardless of whether the cells were hormonally or spontaneously differentiated. EGF stimulation of serum-starved cells increased erbB2 tyrosine phosphorylation and retarded erbB2 migration in SDS-PAGE, suggesting receptor association and activation. Heregulin-alpha1 and -beta1, two EGF related factors, had no effect on erbB2 or EGFR phosphorylation. Although 3T3-L1 cells expressed heregulin, its specific receptors, erbB3 and erbB4, were not found. This is the first time in which erbB2 is reported to be expressed in an adipocytic cell line which does not depend on non EGF family growth factors (thyroid hormone, growth hormone, etc.) to accomplish adipose differentiation. Since erbB2 and EGFR expression were downmodulated as differentiation progressed it is conceivable that a mechanism of switching from a mitogenic to a differentiating signaling pathway may be involved, through regulation of the expression of these

  13. Hyperglycemia and advanced glycation end products (AGEs) suppress the differentiation of 3T3-L1 preadipocytes.

    PubMed

    Chang, Chia-Chu; Chen, Chen-Yu; Chang, Geen-Dong; Chen, Ting-Huan; Chen, Woan-Ling; Wen, Hui-Chin; Huang, Chih-Yang; Chang, Chung-Ho

    2017-08-15

    Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα. Levels or activities of Src, PDK1, Akt, and NF-κB were higher in AGEs- and high glucose-treated cells than those in 3T3-L1 cells. Levels of Bcl-2 were elevated in AGEs- and high glucose-treated cells, and were attenuated by inhibitors of PI3-kinase, Akt and NF-κB. Moreover, adipogenesis was attenuated in 3T3-L1 cells stably expressing Bcl-2 or YAP. These results suggest that chronic AGEs and high glucose treatments up-regulate Bcl-2 and YAP via the Akt-NF-κB pathway and impair adipogenesis.

  14. Hyperglycemia and advanced glycation end products (AGEs) suppress the differentiation of 3T3-L1 preadipocytes

    PubMed Central

    Chang, Geen-Dong; Chen, Ting-Huan; Chen, Woan-Ling; Wen, Hui-Chin; Huang, Chih-Yang; Chang, Chung-Ho

    2017-01-01

    Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα. Levels or activities of Src, PDK1, Akt, and NF-κB were higher in AGEs- and high glucose-treated cells than those in 3T3-L1 cells. Levels of Bcl-2 were elevated in AGEs- and high glucose-treated cells, and were attenuated by inhibitors of PI3-kinase, Akt and NF-κB. Moreover, adipogenesis was attenuated in 3T3-L1 cells stably expressing Bcl-2 or YAP. These results suggest that chronic AGEs and high glucose treatments up-regulate Bcl-2 and YAP via the Akt-NF-κB pathway and impair adipogenesis. PMID:28903400

  15. Recent thymic emigrants are biased against the T-helper type 1 and toward the T-helper type 2 effector lineage.

    PubMed

    Hendricks, Deborah W; Fink, Pamela J

    2011-01-27

    After intrathymic development, T cells exit the thymus and join the peripheral T-cell pool. Such recent thymic emigrants (RTEs) undergo both phenotypic and functional maturation during the first 3 weeks they reside in the periphery. Using a well-controlled in vitro polarization scheme, we now show that CD4(+) RTEs are defective in T-helper (Th) type 0 (Th0), Th1, Th17, and regulatory T-cell lineage commitment, with dampened cytokine production and transcription factor expression. In contrast, CD4(+) RTES are biased toward the Th2 lineage both in vitro and in vivo, with more robust interleukin-4, interleukin-5, and interleukin-13 production than their mature naive counterparts. Coculture experiments demonstrate that mature naive T cells influence neighboring RTEs in their Th responses. In adoptive hosts, CD4(+) RTEs drive production of the Th2-associated antibody isotype immunoglobulin G1 and mediate airway inflammatory disease. This bias in RTEs likely results from dampened negative regulation of the Th2 lineage by diminished levels of T-bet, a key Th1 transcription factor. CD4(+) RTEs thus represent a transitional population with a distinct interpretation of, and response to, immunologic cues. These characteristics may be beneficial during the postthymic maturation period by leading to the avoidance of inappropriate immune responses, particularly in lymphopenic neonates and adults.

  16. Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.

    PubMed

    Kim, Young-Woo; Eom, Bang Wool; Kook, Myeong-Cherl; Kim, Han-Seong; Kim, Mi-Kyung; Hwang, Hai-Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae-Soo; Bae, Chang-Dae; Ro, Jungsil; Hong, Kyeong-Man

    2015-11-06

    Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.

  17. T1 weighted brain images at 7 Tesla unbiased for Proton Density, T2* contrast and RF coil receive B1 sensitivity with simultaneous vessel visualization.

    PubMed

    Van de Moortele, Pierre-François; Auerbach, Edwards J; Olman, Cheryl; Yacoub, Essa; Uğurbil, Kâmil; Moeller, Steen

    2009-06-01

    At high magnetic field, MR images exhibit large, undesirable signal intensity variations commonly referred to as "intensity field bias". Such inhomogeneities mostly originate from heterogeneous RF coil B(1) profiles and, with no appropriate correction, are further pronounced when utilizing rooted sum of square reconstruction with receive coil arrays. These artifacts can significantly alter whole brain high resolution T(1)-weighted (T(1)w) images that are extensively utilized for clinical diagnosis, for gray/white matter segmentation as well as for coregistration with functional time series. In T(1) weighted 3D-MPRAGE sequences, it is possible to preserve a bulk amount of T(1) contrast through space by using adiabatic inversion RF pulses that are insensitive to transmit B(1) variations above a minimum threshold. However, large intensity variations persist in the images, which are significantly more difficult to address at very high field where RF coil B(1) profiles become more heterogeneous. Another characteristic of T(1)w MPRAGE sequences is their intrinsic sensitivity to Proton Density and T(2)(*) contrast, which cannot be removed with post-processing algorithms utilized to correct for receive coil sensitivity. In this paper, we demonstrate a simple technique capable of producing normalized, high resolution T(1)w 3D-MPRAGE images that are devoid of receive coil sensitivity, Proton Density and T(2)(*) contrast. These images, which are suitable for routinely obtaining whole brain tissue segmentation at 7 T, provide higher T(1) contrast specificity than standard MPRAGE acquisitions. Our results show that removing the Proton Density component can help in identifying small brain structures and that T(2)(*) induced artifacts can be removed from the images. The resulting unbiased T(1)w images can also be used to generate Maximum Intensity Projection angiograms, without additional data acquisition, that are inherently registered with T(1)w structural images. In addition

  18. Genes that characterize T3-predominant Graves' thyroid tissues.

    PubMed

    Matsumoto, Chisa; Ito, Mitsuru; Yamada, Hiroya; Yamakawa, Noriko; Yoshida, Hiroshi; Date, Arisa; Watanabe, Mikio; Hidaka, Yoh; Iwatani, Yoshinori; Miyauchi, Akira; Takano, Toru

    2013-02-01

    3,5,3'-Triiodothyronine (T(3))-predominant Graves' disease is characterized by the increasing volume of thyroid goiter resulting in poor prognosis. Although type 1 and type 2 iodothyronine deiodinases (DIO1 and DIO2 respectively) are known to be overexpressed in the thyroid tissues of T(3)-predominant Graves' disease, the pathogenesis of this disease is still unclear. The aim of our study is to identify genes that characterize T(3)-predominant Graves' disease tissue in order to clarify the molecular mechanism of this disease. mRNAs from two thyroid tissues of both typical T(3)-predominant and common-type Graves' disease were analyzed with DNA microarrays with probes for 28 869 genes. Genes identified to be differentially expressed between the two groups were further analyzed in the second and third screenings using 70 Graves' thyroid tissues by real-time quantitative RT-PCR. Twenty-three candidate genes were selected as being differentially expressed in the first screening with microarrays. Among these, seven genes, leucine-rich repeat neuronal 1 (LRRN1), bone morphogenetic protein 8a (BMP8A), N-cadherin (CDH2), phosphodiesterase 1A (PDE1A), creatine kinase mitochondrial 2 (CKMT2), integrin beta-3 (ITGB3), and protein tyrosine phosphatase non-receptor type 4 (PTPN4), were confirmed to be differentially expressed in DIO1 or DIO2 over- and underexpressing Graves' tissues. These genes are related to the characteristics of T(3)-predominant Graves' disease, such as high titer level of serum anti-TSH receptor antibody, high free T(3) to free thyroxine ratio, and a large goiter size. They might play a role in the pathogenesis of T(3)-predominant Graves' disease.

  19. SU-F-R-35: Repeatability of Texture Features in T1- and T2-Weighted MR Images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mahon, R; Weiss, E; Karki, K

    Purpose: To evaluate repeatability of lung tumor texture features from inspiration/expiration MR image pairs for potential use in patient specific care models and applications. Repeatability is a desirable and necessary characteristic of features included in such models. Methods: T1-weighted Volumetric Interpolation Breath-Hold Examination (VIBE) and/or T2-weighted MRI scans were acquired for 15 patients with non-small cell lung cancer before and during radiotherapy for a total of 32 and 34 same session inspiration-expiration breath-hold image pairs respectively. Bias correction was applied to the VIBE (VIBE-BC) and T2-weighted (T2-BC) images. Fifty-nine texture features at five wavelet decomposition ratios were extracted from themore » delineated primary tumor including: histogram(HIST), gray level co-occurrence matrix(GLCM), gray level run length matrix(GLRLM), gray level size zone matrix(GLSZM), and neighborhood gray tone different matrix (NGTDM) based features. Repeatability of the texture features for VIBE, VIBE-BC, T2-weighted, and T2-BC image pairs was evaluated by the concordance correlation coefficient (CCC) between corresponding image pairs, with a value greater than 0.90 indicating repeatability. Results: For the VIBE image pairs, the percentage of repeatable texture features by wavelet ratio was between 20% and 24% of the 59 extracted features; the T2-weighted image pairs exhibited repeatability in the range of 44–49%. The percentage dropped to 10–20% for the VIBE-BC images, and 12–14% for the T2-BC images. In addition, five texture features were found to be repeatable in all four image sets including two GLRLM, two GLZSM, and one NGTDN features. No single texture feature category was repeatable among all three image types; however, certain categories performed more consistently on a per image type basis. Conclusion: We identified repeatable texture features on T1- and T2-weighted MRI scans. These texture features should be further investigated

  20. The XENON1T dark matter experiment

    NASA Astrophysics Data System (ADS)

    Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Antunes, B.; Arneodo, F.; Balata, M.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breskin, A.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Chiarini, A.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Corrieri, R.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; Gangi, P. Di; Giovanni, A. Di; Diglio, S.; Disdier, J.-M.; Doets, M.; Duchovni, E.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Franco, D.; Front, D.; Fulgione, W.; Rosso, A. Gallo; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Giboni, K.-L.; Goetzke, L. W.; Grandi, L.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Huhmann, C.; Itay, R.; James, A.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Maier, R.; Manfredini, A.; Maris, I.; Undagoitia, T. Marrodán; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morå, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Orlandi, D.; Othegraven, R.; Pakarha, P.; Parlati, S.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; García, D. Ramírez; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Santos, J. M. F. dos; Saldanha, R.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Lavina, L. Scotto; Selvi, M.; Shagin, P.; Shockley, E.; Silva, M.; Simgen, H.; Sivers, M. v.; Stern, M.; Stein, A.; Tatananni, D.; Tatananni, L.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Upole, N.; Vargas, M.; Wack, O.; Walet, R.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wittweg, C.; Wulf, J.; Ye, J.; Zhang, Y.

    2017-12-01

    The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.

  1. Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice.

    PubMed

    Sclafani, Anthony; Glass, Damien S; Margolskee, Robert F; Glendinning, John I

    2010-12-01

    Most mammals prefer the sweet taste of sugars, which is mediated by the heterodimeric T1R2+T1R3 taste receptor. Sugar appetite is also enhanced by the post-oral reinforcing actions of the nutrient in the gut. Here, we examined the contribution of gut T1R3 (either alone or as part of the T1R3+T1R3 receptor) to post-oral sugar reinforcement using a flavor-conditioning paradigm. We trained mice to associate consumption of a flavored solution (CS+) with intragastric (IG) infusions of a sweetener, and a different flavored solution (CS-) with IG infusions of water (23 h/day); then, we measured preference in a CS+ vs. CS- choice test. In experiment 1, we predicted that if activation of gut T1R3 mediates sugar reinforcement, then IG infusions of a nutritive (sucrose) or nonnutritive (sucralose) ligand for this receptor should condition a preference for the CS+ in B6 wild-type (WT) mice. While the mice that received IG sucrose infusions developed a strong preference for the CS+, those that received IG sucralose infusions developed a weak avoidance of the CS+. In experiment 2, we used T1R3 knockout (KO) mice to examine the necessity of gut T1R2+T1R3 receptors for conditioned flavor preferences. If intact gut T1R3 (or T1R2+T1R3) receptors are necessary for flavor-sugar conditioning, then T1R3 KO mice should not develop a sugar-conditioned flavor preference. We found that T1R3 KO mice, like WT mice, acquired a strong preference for the CS+ paired with IG sucrose infusions. The KO mice were also like WT mice in avoiding a CS+ flavor paired with IG sucralose infusions These findings provide clear evidence that gut T1R3 receptors are not necessary for sugar-conditioned flavor preferences or sucralose-induced flavor avoidance in mice.

  2. High-resolution 3D-constructive interference in steady-state MR imaging and 3D time-of-flight MR angiography in neurovascular compression: a comparison between 3T and 1.5T.

    PubMed

    Garcia, M; Naraghi, R; Zumbrunn, T; Rösch, J; Hastreiter, P; Dörfler, A

    2012-08-01

    High-resolution MR imaging is useful for diagnosis and preoperative planning in patients with NVC. Because high-field MR imaging promises higher SNR and resolution, the aim of this study was to determine the value of high-resolution 3D-CISS and 3D-TOF MRA at 3T compared with 1.5T in patients with NVC. Forty-seven patients with NVC, trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia were examined at 1.5T and 3T, including high-resolution 3D-CISS and 3D-TOF MRA sequences. Delineation of anatomic structures, overall image quality, severity of artifacts, visibility of NVC, and assessment of the SNR and CNR were compared between field strengths. SNR and CNR were significantly higher at 3T (P < .001). Significantly better anatomic conspicuity, including delineation of CNs, nerve branches, and assessment of small vessels, was obtained at 3T (P < .02). Severity of artifacts was significantly lower at 3T (P < .001). Consequently, overall image quality was significantly higher at 3T. NVC was significantly better delineated at 3T (P < .001). Six patients in whom NVC was not with certainty identifiable at 1.5T were correctly diagnosed at 3T. Patients with NVC may benefit from the higher resolution and greater sensitivity of 3T for preoperative assessment of NVC, and 3T may be of particular value when 1.5T is equivocal.

  3. The GEM-T2 gravitational model

    NASA Technical Reports Server (NTRS)

    Marsh, J. G.; Lerch, F. J.; Putney, B. H.; Felsentreger, T. L.; Sanchez, B. V.; Klosko, S. M.; Patel, G. B.; Robbins, J. W.; Williamson, R. G.; Engelis, T. E.

    1989-01-01

    The GEM-T2 is the latest in a series of Goddard Earth Models of the terrestrial field. It was designed to bring modeling capabilities one step closer towards ultimately determining the TOPEX/Poseidon satellite's radial position to an accuracy of 10-cm RMS (root mean square). It also improves models of the long wavelength geoid to support many oceanographic and geophysical applications. The GEM-T2 extends the spherical harmonic field to include more than 600 coefficients above degree 36 (which was the limit for its predecessor, GEM-T1). Like GEM-T1, it was produced entirely from satellite tracking data, but it now uses nearly twice as many satellites (31 vs. 17), contains four times the number of observations (2.4 million), has twice the number of data arcs (1132), and utilizes precise laser tracking from 11 satellites. The estimation technique for the solution has been augmented to include an optimum data weighting procedure with automatic error calibration for the gravitational parameters. Results for the GEM-T2 error calibration indicate significant improvement over previous satellite-only models. The error of commission in determining the geoid has been reduced from 155 cm in GEM-T1 to 105 cm for GEM-T2 for the 36 x 36 portion of the field, and 141 cm for the entire model. The orbital accuracies achieved using GEM-T2 are likewise improved. Also, the projected radial error on the TOPEX satellite orbit indicates 9.4 cm RMS for GEM-T2, compared to 24.1 cm for GEM-T1.

  4. T2 mapping in patellar chondromalacia.

    PubMed

    Ruiz Santiago, Fernando; Pozuelo Calvo, Rocío; Almansa López, Julio; Guzmán Álvarez, Luis; Castellano García, María Del Mar

    2014-06-01

    To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia. This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16-45 years). MRI of 97 knees were performed in these patients at 1.5T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet-proximal-lateral (EPL), external facet-proximal-central (EPC), internal facet-proximal-central (IPC), internal facet-proximal-medial (IPM), 4 in the middle section (external facet-middle-lateral (EML), external facet-middle-central (EMC), internal facet-middle-central (IMC), internal facet-middle-medial (IMM) and 4 distal (external facet-distal-lateral (EDL), external facet-distal-central (EDC), internal facet-distal-central (IDC), internal facet-distal-medial (IDM). T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p<0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p<0.05). Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased. Copyright © 2014 Elsevier

  5. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lai, Peng-Yeh; Tsai, Chong-Bin; Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCRmore » analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.« less

  6. Simultaneous Quantitative MRI Mapping of T1, T2* and Magnetic Susceptibility with Multi-Echo MP2RAGE

    PubMed Central

    Kober, Tobias; Möller, Harald E.; Schäfer, Andreas

    2017-01-01

    The knowledge of relaxation times is essential for understanding the biophysical mechanisms underlying contrast in magnetic resonance imaging. Quantitative experiments, while offering major advantages in terms of reproducibility, may benefit from simultaneous acquisitions. In this work, we demonstrate the possibility of simultaneously recording relaxation-time and susceptibility maps with a prototype Multi-Echo (ME) Magnetization-Prepared 2 RApid Gradient Echoes (MP2RAGE) sequence. T1 maps can be obtained using the MP2RAGE sequence, which is relatively insensitive to inhomogeneities of the radio-frequency transmit field, B1+. As an extension, multiple gradient echoes can be acquired in each of the MP2RAGE readout blocks, which permits the calculation of T2* and susceptibility maps. We used computer simulations to explore the effects of the parameters on the precision and accuracy of the mapping. In vivo parameter maps up to 0.6 mm nominal resolution were acquired at 7 T in 19 healthy volunteers. Voxel-by-voxel correlations and the test-retest reproducibility were used to assess the reliability of the results. When using optimized paramenters, T1 maps obtained with ME-MP2RAGE and standard MP2RAGE showed excellent agreement for the whole range of values found in brain tissues. Simultaneously obtained T2* and susceptibility maps were of comparable quality as Fast Low-Angle SHot (FLASH) results. The acquisition times were more favorable for the ME-MP2RAGE (≈ 19 min) sequence as opposed to the sum of MP2RAGE (≈ 12 min) and FLASH (≈ 10 min) acquisitions. Without relevant sacrifice in accuracy, precision or flexibility, the multi-echo version may yield advantages in terms of reduced acquisition time and intrinsic co-registration, provided that an appropriate optimization of the acquisition parameters is performed. PMID:28081157

  7. Rotation relaxation splitting for optimizing parallel RF excitation pulses with T1 - and T2 -relaxations in MRI

    NASA Astrophysics Data System (ADS)

    Majewski, Kurt

    2018-03-01

    Exact solutions of the Bloch equations with T1 - and T2 -relaxation terms for piecewise constant magnetic fields are numerically challenging. We therefore investigate an approximation for the achieved magnetization in which rotations and relaxations are split into separate operations. We develop an estimate for its accuracy and explicit first and second order derivatives with respect to the complex excitation radio frequency voltages. In practice, the deviation between an exact solution of the Bloch equations and this rotation relaxation splitting approximation seems negligible. Its computation times are similar to exact solutions without relaxation terms. We apply the developed theory to numerically optimize radio frequency excitation waveforms with T1 - and T2 -relaxations in several examples.

  8. T1ρ MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration

    PubMed Central

    Witschey, Walter RT; Borthakur, Arijitt; Fenty, Matt; Kneeland, J Bruce; Lonner, Jess H; McArdle, Erin L.; Sochor, Matt; Reddy, Ravinder

    2010-01-01

    9 asymptomatic subjects and 6 patients underwent T1ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 23 months post-arthroscopy using sagittal T1-weighted and axial and coronal T1ρ MRI from which spatial T1ρ relaxation maps were calculated from segmented T1-weighted images. Median T1ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (p < 0.001) and median T1ρ exceeded asymptomatic articular cartilage median T1ρ by 2.5 to 9.2 ms. In 8 observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1ρ was elevated in 5, but in all observations, large foci of increased T1ρ were observed. It was determined that T1ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. PMID:20432308

  9. Biochemical magnetic resonance imaging of knee articular cartilage: T1rho and T2 mapping as cartilage degeneration biomarkers.

    PubMed

    Le, Jenna; Peng, Qi; Sperling, Karen

    2016-11-01

    Osteoarthritis (OA) is a disease whose hallmark is the degeneration of articular cartilage. There is a worsening epidemic of OA in the United States today, with considerable economic costs. In order to develop more effective treatments for OA, noninvasive biomarkers that permit early diagnosis and treatment monitoring are necessary. T1rho and T2 mapping are two magnetic resonance imaging techniques that have shown great promise as noninvasive biomarkers of cartilage degeneration. Each of the two techniques is endowed with advantages and disadvantages: T1rho can discern earlier biochemical changes of OA than T2 mapping, while T2 mapping is more widely available and can be incorporated into existing imaging protocols in a more time-efficient manner than T1rho. Both techniques have been applied in numerous instances to study how cartilage is affected by OA risk factors, such as age and exercise. Additionally, both techniques have been repeatedly applied to the study of posttraumatic OA in patients with torn anterior cruciate ligaments. © 2016 New York Academy of Sciences.

  10. Spherically symmetric vacuum in covariant F (T )=T +α/2 T2+O (Tγ) gravity theory

    NASA Astrophysics Data System (ADS)

    DeBenedictis, Andrew; Ilijić, Saša

    2016-12-01

    Recently, a fully covariant version of the theory of F (T ) torsion gravity has been introduced by M. Kršśák and E. Saridakis [Classical Quantum Gravity 33, 115009 (2016)]. In covariant F (T ) gravity, the Schwarzschild solution is not a vacuum solution for F (T )≠T , and therefore determining the spherically symmetric vacuum is an important open problem. Within the covariant framework, we perturbatively solve the spherically symmetric vacuum gravitational equations around the Schwarzschild solution for the scenario with F (T )=T +(α /2 )T2 , representing the dominant terms in theories governed by Lagrangians analytic in the torsion scalar. From this, we compute the perihelion shift correction to solar system planetary orbits as well as perturbative gravitational effects near neutron stars. This allows us to set an upper bound on the magnitude of the coupling constant, α , which governs deviations from general relativity. We find the bound on this nonlinear torsion coupling constant by specifically considering the uncertainty in the perihelion shift of Mercury. We also analyze a bound from a similar comparison with the periastron orbit of the binary pulsar PSR J0045-7319 as an independent check for consistency. Setting bounds on the dominant nonlinear coupling is important in determining if other effects in the Solar System or greater universe could be attributable to nonlinear torsion.

  11. [Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms].

    PubMed

    Isakova, Zh T; Talaibekova, E T; Asambaeva, D A; Kerimkulova, A S; Lunegova, O S; Aldasheva, N M; Aldashev, A A

    To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T

  12. Lewis type 1 antigen synthase (beta3Gal-T5) is transcriptionally regulated by homeoproteins.

    PubMed

    Isshiki, Soichiro; Kudo, Takashi; Nishihara, Shoko; Ikehara, Yuzuru; Togayachi, Akira; Furuya, Akiko; Shitara, Kenya; Kubota, Tetsuro; Watanabe, Masahiko; Kitajima, Masaki; Narimatsu, Hisashi

    2003-09-19

    The type 1 carbohydrate chain, Galbeta1-3GlcNAc, is synthesized by UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T). Among six beta3Gal-Ts cloned to date, beta3Gal-T5 is an essential enzyme for the synthesis of type 1 chain in epithelium of digestive tracts or pancreatic tissue. It forms the type 1 structure on glycoproteins produced from such tissues. In the present study, we found that the transcriptional regulation of the beta3Gal-T5 gene is controlled by homeoproteins, i.e. members of caudal-related homeobox protein (Cdx) and hepatocyte nuclear factor (HNF) families. We found an important region (-151 to -121 from the transcription initiation site), named the beta3Gal-T5 control element (GCE), for the promoter activity. GCE contained the consensus sequences for members of the Cdx and HNF families. Mutations introduced into this sequence abolished the transcriptional activity. Four factors, Cdx1, Cdx2, HNF1alpha, and HNF1beta, could bind to GCE and transcriptionally activate the beta3Gal-T5 gene. Transcriptional regulation of the beta3Gal-T5 gene was consistent with that of members of the Cdx and HNF1 families in two in vivo systems. 1) During in vitro differentiation of Caco-2 cells, transcriptional up-regulation of beta3Gal-T5 was observed in correlation with the increase in transcripts for Cdx2 and HNF1alpha. 2) Both transcript and protein levels of beta3Gal-T5 were determined to be significantly reduced in colon cancer. This down-regulation was correlated with the decrease of Cdx1 and HNF1beta expression in cancer tissue. This is the first finding that a glycosyltransferase gene is transcriptionally regulated under the control of homeoproteins in a tissue-specific manner. beta3Gal-T5, controlled by the intestinal homeoproteins, may play an important role in the specific function of intestinal cells by modifying the carbohydrate structure of glycoproteins.

  13. Temperature induced modulation of lipid oxidation and lipid accumulation in palmitate-mediated 3T3-L1 adipocytes and 3T3-L1 adipocytes.

    PubMed

    Lin, Xiaofen; Li, Yi; Leung, Polly Hangmei; Li, Jiashen; Hu, Junyan; Liu, Xuan; Li, Zhi

    2016-05-01

    Human skin temperature can vary widely depending on anatomical location and ambient temperature. It is also known that local changes in skin and subcutaneous temperature can affect fat metabolism. This study aimed to explore the potential effects of surrounding thermal environment on fat by investigating cell viability, lipid oxidation, and lipid accumulation in 3T3-L1 adipocytes and palmitate-treated adipocytes after 4h incubation. No significant differences of viability in 3T3-L1 adipocytes were detected under different temperature conditions. Despite no significant increase being observed under warm temperature (39°C) conditions, a similarly significant suppression of intracellular reactive oxygen species (ROS) and lipid peroxidation were found in 3T3-L1 adipocytes and palmitate-treated adipocytes under 4h exposure to cooler temperatures of 31-33°C (P<0.01). ROS, chemically reactive molecules containing oxygen, are currently understood to be a major contributor to oxidantive stress in obesity. Additionally, cooler temperatures (31-33°C) could improve the size of lipid droplets in 3T3-L1 adipocytes (P<0.01), but no significant effect was generated by temperature change on lipid droplets in palmitate-treated adipocytes. In the palmitate-induced adiposity model, although excessive ROS and lipid peroxidation has been attenuated by temperature decrease (P<0.01), it still does not positively modulate lipid droplet size (P>0.05) and remedy the palmitate damage induced cell death (P<0.01). These findings provide preliminary support for potential interventions based on temperature manipulation for cell metabolism of adipocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

    PubMed Central

    Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

    2009-01-01

    Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

  15. Myocardial T1 mapping at 3.0 tesla using an inversion recovery spoiled gradient echo readout and bloch equation simulation with slice profile correction (BLESSPC) T1 estimation algorithm.

    PubMed

    Shao, Jiaxin; Rapacchi, Stanislas; Nguyen, Kim-Lien; Hu, Peng

    2016-02-01

    To develop an accurate and precise myocardial T1 mapping technique using an inversion recovery spoiled gradient echo readout at 3.0 Tesla (T). The modified Look-Locker inversion-recovery (MOLLI) sequence was modified to use fast low angle shot (FLASH) readout, incorporating a BLESSPC (Bloch Equation Simulation with Slice Profile Correction) T1 estimation algorithm, for accurate myocardial T1 mapping. The FLASH-MOLLI with BLESSPC fitting was compared with different approaches and sequences with regards to T1 estimation accuracy, precision and image artifact based on simulation, phantom studies, and in vivo studies of 10 healthy volunteers and three patients at 3.0 Tesla. The FLASH-MOLLI with BLESSPC fitting yields accurate T1 estimation (average error = -5.4 ± 15.1 ms, percentage error = -0.5% ± 1.2%) for T1 from 236-1852 ms and heart rate from 40-100 bpm in phantom studies. The FLASH-MOLLI sequence prevented off-resonance artifacts in all 10 healthy volunteers at 3.0T. In vivo, there was no significant difference between FLASH-MOLLI-derived myocardial T1 values and "ShMOLLI+IE" derived values (1458.9 ± 20.9 ms versus 1464.1 ± 6.8 ms, P = 0.50); However, the average precision by FLASH-MOLLI was significantly better than that generated by "ShMOLLI+IE" (1.84 ± 0.36% variance versus 3.57 ± 0.94%, P < 0.001). The FLASH-MOLLI with BLESSPC fitting yields accurate and precise T1 estimation, and eliminates banding artifacts associated with bSSFP at 3.0T. © 2015 Wiley Periodicals, Inc.

  16. SU-F-I-16: Short Breast MRI with High-Resolution T2-Weighted and Dynamic Contrast Enhanced T1-Weighted Images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, J; Son, J; Arun, B

    Purpose: To develop and demonstrate a short breast (sb) MRI protocol that acquires both T2-weighted and dynamic contrast-enhanced T1-weighted images in approximately ten minutes. Methods: The sb-MRI protocol consists of two novel pulse sequences. The first is a flexible fast spin-echo triple-echo Dixon (FTED) sequence for high-resolution fat-suppressed T2-weighted imaging, and the second is a 3D fast dual-echo spoiled gradient sequence (FLEX) for volumetric fat-suppressed T1-weighted imaging before and post contrast agent injection. The flexible FTED sequence replaces each single readout during every echo-spacing period of FSE with three fast-switching bipolar readouts to produce three raw images in a singlemore » acquisition. These three raw images are then post-processed using a Dixon algorithm to generate separate water-only and fat-only images. The FLEX sequence acquires two echoes using dual-echo readout after each RF excitation and the corresponding images are post-processed using a similar Dixon algorithm to yield water-only and fat-only images. The sb-MRI protocol was implemented on a 3T MRI scanner and used for patients who had undergone concurrent clinical MRI for breast cancer screening. Results: With the same scan parameters (eg, spatial coverage, field of view, spatial and temporal resolution) as the clinical protocol, the total scan-time of the sb-MRI protocol (including the localizer, bilateral T2-weighted, and dynamic contrast-enhanced T1-weighted images) was 11 minutes. In comparison, the clinical breast MRI protocol took 43 minutes. Uniform fat suppression and high image quality were consistently achieved by sb-MRI. Conclusion: We demonstrated a sb-MRI protocol comprising both T2-weighted and dynamic contrast-enhanced T1-weighted images can be performed in approximately ten minutes. The spatial and temporal resolution of the images easily satisfies the current breast MRI accreditation guidelines by the American College of Radiology. The protocol

  17. T1 weighted Brain Images at 7 Tesla Unbiased for Proton Density, T2* contrast and RF Coil Receive B1 Sensitivity with Simultaneous Vessel Visualization

    PubMed Central

    Van de Moortele, Pierre-François; Auerbach, Edwards J.; Olman, Cheryl; Yacoub, Essa; Uğurbil, Kâmil; Moeller, Steen

    2009-01-01

    At high magnetic field, MR images exhibit large, undesirable signal intensity variations commonly referred to as “intensity field bias”. Such inhomogeneities mostly originate from heterogeneous RF coil B1 profiles and, with no appropriate correction, are further pronounced when utilizing rooted sum of square reconstruction with receive coil arrays. These artifacts can significantly alter whole brain high resolution T1-weighted (T1w) images that are extensively utilized for clinical diagnosis, for gray/white matter segmentation as well as for coregistration with functional time series. In T1 weighted 3D-MPRAGE sequences, it is possible to preserve a bulk amount of T1 contrast through space by using adiabatic inversion RF pulses that are insensitive to transmit B1 variations above a minimum threshold. However, large intensity variations persist in the images, which are significantly more difficult to address at very high field where RF coil B1 profiles become more heterogeneous. Another characteristic of T1w MPRAGE sequences is their intrinsic sensitivity to Proton Density and T2* contrast, which cannot be removed with post-processing algorithms utilized to correct for receive coil sensitivity. In this paper, we demonstrate a simple technique capable of producing normalized, high resolution T1w 3D-MPRAGE images that are devoid of receive coil sensitivity, Proton Density and T2* contrast. These images, which are suitable for routinely obtaining whole brain tissue segmentation at 7 Tesla, provide higher T1 contrast specificity than standard MPRAGE acquisitions. Our results show that removing the Proton Density component can help identifying small brain structures and that T2* induced artifacts can be removed from the images. The resulting unbiased T1w images can also be used to generate Maximum Intensity Projection angiograms, without additional data acquisition, that are inherently registered with T1w structural images. In addition, we introduce a simple technique

  18. 3T deep gray matter T2 hypointensity correlates with disability over time in stable relapsing-remitting multiple sclerosis: a 3-year pilot study.

    PubMed

    Zhang, Y; Metz, L M; Yong, V W; Mitchell, J R

    2010-10-15

    Abnormally decreased deep gray matter (GM) signal intensity on T2-weighted MRI (T2 hypointensity) is associated with brain atrophy and disability progression in patients with multiple sclerosis (MS) and is believed to represent excessive iron deposition. We investigated the time course of deep GM T2 hypointensity and its relationship with disability at 3T in 8 stable relapsing-remitting (RR) MS patients treated with minocycline over 3years. MRI and disability measurements were compared at baseline, 6, 12, 24, and 36months. Grand mean deep GM T2 hypointensity was negatively correlated with EDSS over time (r=-0.94, P=0.02). This correlation was strongest in the head of caudate (r=-0.95, P=0.01) and putamen (r=-0.89, P=0.04). Additionally, baseline grand mean deep GM T2 hypointensity appears to predict third year EDSS (r=-0.72, P=0.04). These results suggest that iron associated deep GM injury correlates with patient disability in stable RRMS. Measurements of deep GM T2 hypointensity at high field MRI may prove to be useful in monitoring individuals with MS. Further studies are required to confirm these results in a large sample and to determine if T2 hypointensity changes in clinically active MS patients. Copyright 2010 Elsevier B.V. All rights reserved.

  19. [Evaluation of Artificial Hip Joint with Radiofrequency Heating Issues during MRI Examination: A Comparison between 1.5 T and 3 T].

    PubMed

    Yamazaki, Masaru; Ideta, Takahiro; Kudo, Sadahiro; Nakazawa, Masami

    2016-06-01

    In magnetic resonance imaging (MRI), when radiofrequency (RF) is irradiated to a subject with metallic implant, it can generate heat by RF irradiation. Recently 3 T MRI scanner has spread widely and imaging for any regions of whole body has been conducted. However specific absorption rate (SAR) of 3 T MRI becomes approximately four times as much as the 1.5 T, which can significantly affect the heat generation of metallic implants. So, we evaluated RF heating of artificial hip joints in different shapes and materials in 1.5 T and 3 T MRI. Three types of artificial hip joints made of stainless alloy, titanium alloy and cobalt chrome alloy were embedded in the human body-equivalent phantom respectively and their temperature change were measured for twenty minutes by 1.5 T and 3 T MRI. The maximum temperature rise was observed at the bottom head in all of three types of artificial hip joints, the rise being 12°C for stainless alloy, 11.9°C for titanium alloy and 6.1°C for cobalt chrome alloy in 1.5 T. The temperature rise depended on SAR and the increase of SAR had a good linear relationship with the temperature rise. It was found from the result that the RF heating of metallic implants can take place in various kinds of material and the increase of SAR has a good linear relationship with the temperature rise. This experience shows that reduction of SAR can decrease temperature of metallic implants.

  20. 6-gingerol inhibits rosiglitazone-induced adipogenesis in 3T3-L1 adipocytes.

    PubMed

    Tzeng, Thing-Fong; Chang, Chia Ju; Liu, I-Min

    2014-02-01

    We investigated the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) on the inhibition of rosiglitazone (RGZ)-induced adipogenesis in 3T3-L1 cells. The morphological changes were photographed based on staining lipid accumulation by Oil-Red O in RGZ (1 µmol/l)-treated 3T3-L1 cells without or with various concentrations of 6-gingerol on differentiation day 8. Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction. Differentiated cells were lysed to detect mRNA and protein levels of adipocyte-specific transcription factors by real-time reverse transcription-polymerase chain reaction and Western blot analysis, respectively. 6-gingerol (50 µmol/l) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ-induced adipocyte differentiation in 3T3-L1 cells. The triglyceride accumulation induced by RGZ in differentiated 3T3-L1 cells was also reduced by 6-gingerol (50 µmol/l). Treatment of differentiated 3T3-L1 cells with 6-gingerol (50 µmol/l) antagonized RGZ-induced gene expression of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein α. Additionally, the increased levels of mRNA and protein in adipocyte-specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3-L1 cells were decreased upon treatment with 6-gingerol. Our data suggests that 6-gingerol may be beneficial in obesity, by reducing adipogenesis partly through the down-regulating PPARγ activity. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.

    PubMed

    Hegazy, Ahmed N; Peine, Michael; Helmstetter, Caroline; Panse, Isabel; Fröhlich, Anja; Bergthaler, Andreas; Flatz, Lukas; Pinschewer, Daniel D; Radbruch, Andreas; Löhning, Max

    2010-01-29

    Current T cell differentiation models invoke separate T helper 2 (Th2) and Th1 cell lineages governed by the lineage-specifying transcription factors GATA-3 and T-bet. However, knowledge on the plasticity of Th2 cell lineage commitment is limited. Here we show that infection with Th1 cell-promoting lymphocytic choriomeningitis virus (LCMV) reprogrammed otherwise stably committed GATA-3(+) Th2 cells to adopt a GATA-3(+)T-bet(+) and interleukin-4(+)interferon-gamma(+) "Th2+1" phenotype that was maintained in vivo for months. Th2 cell reprogramming required T cell receptor stimulation, concerted type I and type II interferon and interleukin-12 signals, and T-bet. LCMV-triggered T-bet induction in adoptively transferred virus-specific Th2 cells was crucial to prevent viral persistence and fatal immunopathology. Thus, functional reprogramming of unfavorably differentiated Th2 cells may facilitate the establishment of protective immune responses. Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells. Copyright 2010 Elsevier Inc. All rights reserved.

  2. T2 relaxation times of the glenohumeral joint at 3.0 T MRI in patients with and without primary and secondary osteoarthritis.

    PubMed

    Lee, So-Yeon; Park, Hee-Jin; Kwon, Heon-Ju; Kim, Mi Sung; Choi, Seon Hyeong; Choi, Yoon Jung; Kim, Eugene

    2015-11-01

    Quantitative magnetic resonance imaging (MRI) of cartilage has recently been applied to patients with osteoarthritis (OA). T2 mapping is a sensitive method of detecting changes in the chemical composition and structure of cartilage. To establish baseline T2 values of glenohumeral joint cartilage at 3.0 T and compare T2 values among subjects with and without OA. The study involved 30 patients (18 women, 12 men; median age, 67 years; age range, 51-78 years) with primary (n = 7) and secondary OA (n = 23) in the glenohumeral joint and 34 subjects without OA (19 women, 15 men; median age, 49 years; age range, 23-63 years). All subjects were evaluated by radiography and 3.0 T MRI including a multi-echo T2-weighted spin echo pulse sequence. The T2 value of the cartilage was measured by manually drawing the region of interest on the T2 map. Per-zone comparison of T2 values was performed using Mann-Whitney U test. Median T2 values differed significantly between subjects without OA (36.00 ms [interquartile range, 33.89-37.31 ms]) and those with primary (37.52 ms [36.84-39.11], P = 0.028), but not secondary (36.87 ms [34.70-41.10], P = 0.160) OA. Glenohumeral cartilage T2 values were higher in different zones between patients with primary and secondary OA than in subjects without OA. These T2 values can be used for comparison to assess cartilage degeneration in patients with shoulder OA. Significant differences in T2 were observed among subjects without OA and those with primary and secondary OA. © The Foundation Acta Radiologica 2014.

  3. CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells

    PubMed Central

    Zhang, Xiaolong; Chang Li, Xian; Xiao, Xiang; Sun, Rui; Tian, Zhigang; Wei, Haiming

    2013-01-01

    The peripheral Foxp3+ Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4+ T cells can be readily converted to Foxp3+ iTreg in vitro, and memory CD4+ T cells are resistant to conversion. In this study, we investigated the induction of Foxp3+ T cells from various CD4+ T-cell subsets in human peripheral blood. Though naive CD4+ T cells were readily converted to Foxp3+ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3+ T cells did not express the memory marker CD45RO as do Foxp3+ T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4+ T cells, defined as CD62L+ central memory T cells, could be induced by TGF-β to differentiate into Foxp3+ T cells. It is well known that Foxp3+ T cells derived from human CD4+CD25- T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4+CD62L+ central memory T cell-derived Foxp3+ T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4+ T cell-derived Foxp3+ T cells. But further research showed that mouse CD4+ central memory T cells also could be induced to differentiate into Foxp3+ T cells, such Foxp3+ T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4+CD62L+ central memory T cells as a novel potential source of iTreg. PMID:24155942

  4. The importance of the presence of a 5'-ribonucleotide and the contribution of the T1R1 + T1R3 heterodimer and an additional low-affinity receptor in the taste detection of L-glutamate as assessed psychophysically.

    PubMed

    Smith, Kimberly R; Spector, Alan C

    2014-09-24

    The molecular receptors underlying the purported "umami" taste quality commonly associated with l-glutamate have been controversial. Evidence supports the involvement of the T1R1 + T1R3 heterodimer, a GPCR broadly tuned to l-amino acids, but variants of two mGluRs expressed in taste buds have also been implicated. Using a rigorous psychophysical taste-testing paradigm, we demonstrated impaired, if not eliminated, detection of MSG in WT and T1R1, T1R2, T1R3, and T1R2 + T1R3 KO mice when the contribution of sodium was minimized by the epithelial sodium channel blocker amiloride. When inosine 5'-monophosphate (IMP), a ribonucleotide that potentiates the l-glutamate signal through the T1R1 + T1R3 heterodimer, was added, the WT and T1R2 KO mice were able to detect the compound stimulus across all MSG (+amiloride) concentrations due, in part, to the taste of IMP. In contrast, mice lacking T1R1 or T1R3 could not detect IMP alone, yet some were able to detect MSG + amiloride + IMP, but only at the higher MSG concentrations. Interestingly, the sensitivity of T1R1 KO mice to another l-amino acid, lysine, was unimpaired, suggesting that some l-amino acids can be detected through T1R1 + T1R3-independent receptors without sensitivity loss. Given that IMP is not thought to affect mGluRs, behavioral detection of l-glutamate appears to require the contribution of the T1R1 + T1R3 receptor. However, the partial competence observed in some T1R1 and T1R3 KO mice when MSG + amiloride + IMP was tested suggests that a T1R1 or T1R3 homodimer or an unidentified protein, perhaps in conjunction with T1R1 or T1R3, can serve as a low-affinity taste receptor for l-glutamate in the presence of IMP. Copyright © 2014 the authors 0270-6474/14/3413234-12$15.00/0.

  5. Metal Flux Growth, Structural Relations, and Physical Properties of EuCu2Ge2 and Eu3T2In9 (T = Cu and Ag).

    PubMed

    Subbarao, Udumula; Roy, Soumyabrata; Sarma, Saurav Ch; Sarkar, Sumanta; Mishra, Vidyanshu; Khulbe, Yatish; Peter, Sebastian C

    2016-10-17

    Single crystals (SCs) of the compounds Eu 3 Ag 2 In 9 and EuCu 2 Ge 2 were synthesized through the reactions run in liquid indium. Eu 3 Ag 2 In 9 crystallizes in the La 3 Al 11 structure type [orthorhombic space group (SG) Immm] with the lattice parameters: a = 4.8370(1) Å, b = 10.6078(3) Å, and c = 13.9195(4) Å. EuCu 2 Ge 2 crystallizes in the tetragonal ThCr 2 Si 2 structure type (SG I4/mmm) with the lattice parameters: a = b = 4.2218(1) Å, and c = 10.3394(5) Å. The crystal structure of Eu 3 Ag 2 In 9 is comprised of edge-shared hexagonal rings consisting of indium. The one-dimensional chains of In 6 rings are shared through the edges, which are further interconnected with other six-membered rings forming a three-dimensional (3D) stable crystal structure along the bc plane. The crystal structure of EuCu 2 Ge 2 can be explained as the complex [CuGe] (2+δ)- polyanionic network embedded with Eu ions. These polyanionic networks present in the crystal structure of EuCu 2 Ge 2 are shared through the edges of the 011 plane containing Cu and Ge atoms, resulting in a 3D network. The structural relationship between Eu 3 T 2 In 9 and EuCu 2 Ge 2 has been discussed in detail, and we conclude that Eu 3 T 2 In 9 is the metal deficient variant of EuCu 2 Ge 2 . The magnetic susceptibilities of Eu 3 T 2 In 9 (T = Cu and Ag) and EuCu 2 Ge 2 were measured between 2 and 300 K. In all cases, magnetic susceptibility data followed Curie-Weiss law above 150 K. Magnetic moment values obtained from the measurements indicate the probable mixed/intermediate valent behavior of the europium atoms, which was further confirmed by X-ray absorption studies and bond distances around the Eu atoms. Electrical resistivity measurements suggest that Eu 3 T 2 In 9 and EuCu 2 Ge 2 are metallic in nature.

  6. Quantitative T1 and T2* carotid atherosclerotic plaque imaging using a three-dimensional multi-echo phase-sensitive inversion recovery sequence: a feasibility study.

    PubMed

    Fujiwara, Yasuhiro; Maruyama, Hirotoshi; Toyomaru, Kanako; Nishizaka, Yuri; Fukamatsu, Masahiro

    2018-06-01

    Magnetic resonance imaging (MRI) is widely used to detect carotid atherosclerotic plaques. Although it is important to evaluate vulnerable carotid plaques containing lipids and intra-plaque hemorrhages (IPHs) using T 1 -weighted images, the image contrast changes depending on the imaging settings. Moreover, to distinguish between a thrombus and a hemorrhage, it is useful to evaluate the iron content of the plaque using both T 1 -weighted and T 2 *-weighted images. Therefore, a quantitative evaluation of carotid atherosclerotic plaques using T 1 and T 2 * values may be necessary for the accurate evaluation of plaque components. The purpose of this study was to determine whether the multi-echo phase-sensitive inversion recovery (mPSIR) sequence can improve T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of an IPH. T 1 and T 2 * values measured using mPSIR were compared to values from conventional methods in phantom and in vivo studies. In the phantom study, the T 1 and T 2 * values estimated using mPSIR were linearly correlated with those of conventional methods. In the in vivo study, mPSIR demonstrated higher T 1 contrast between the IPH phantom and sternocleidomastoid muscle than the conventional method. Moreover, the T 1 and T 2 * values of the blood vessel wall and sternocleidomastoid muscle estimated using mPSIR were correlated with values measured by conventional methods and with values reported previously. The mPSIR sequence improved T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of the neck region. Although further study is required to evaluate the clinical utility, mPSIR may improve carotid atherosclerotic plaque detection and provide detailed information about plaque components.

  7. Fluorescence lifetime imaging of lipids during 3T3-L1 cell differentiation

    NASA Astrophysics Data System (ADS)

    Song, Young Sik; Won, Young Jae; Lee, Sang-Hak; Kim, Dug Young

    2014-03-01

    Obesity is becoming a big health problem in these days. Since increased body weight is due to increased number and size of the triglyceride-storing adipocytes, many researchers are working on differentiation conditions and processes of adipocytes. Adipocytes also work as regulators of whole-body energy homeostasis by secreting several proteins that regulate processes as diverse as haemostasis, blood pressure, immune function, angiogenesis and energy balance. 3T3-L1 cells are widely used cell line for studying adipogenesis because it can differentiate into an adipocyte-like phenotype under appropriate conditions. In this paper, we propose an effective fluorescence lifetime imaging technique which can easily distinguish lipids in membrane and those in lipid droplets. Nile red dyes are attached to lipids in 3T3-L1 cells. Fluorescence lifetime images were taken for 2 week during differentiation procedure of 3T3-L1 cells into adipocytes. We used 488 nm pulsed laser with 5MHz repetition rate and emission wavelength is 520 nm of Nile Red fluorescent dye. Results clearly show that the lifetime of Nile red in lipid droplets are smaller than those in cell membrane. Our results suggest that fluorescence lifetime imaging can be a very powerful tool to monitor lipid droplet formation in adipocytes from 3T3-L1 cells.

  8. Osteogenic gene expression of murine osteoblastic (MC3T3-E1) cells under cyclic tension

    NASA Astrophysics Data System (ADS)

    Kao, C. T.; Chen, C. C.; Cheong, U.-I.; Liu, S. L.; Huang, T. H.

    2014-08-01

    Low-level laser therapy (LLLT) can promote cell proliferation. The remodeling ability of the tension side of orthodontic teeth affects post-orthodontic stability. The purpose of the present study was to investigate the osteogenic effects of LLLT on osteoblast-like cells treated with a simulated tension system that provides a mechanical tension regimen. Murine osteoblastic (MC3T3-E1) cells were cultured in a Flexcell strain unit with programmed loads of 12% elongation at a frequency of 0.5 Hz for 24 and 48 h. The cultured cells were treated with a low-level diode laser using powers of 5 J and 10 J. The proliferation of MC3T3-E1 cells was determined using the Alamar Blue assay. The expression of osteogenic genes (type I collagen (Col-1), osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphologic protein (BMP-2), and bone morphologic protein (BMP-4)) in MC3T3-E1 cells was analyzed using reverse transcription polymerase chain reaction (RT-PCR). The data were analyzed using one-way analysis of variance. The proliferation rate of tension-cultured MC3T3-E1 cells under 5 J and 10 J LLLT increased compared with that of the control group (p < 0.05). Prominent mineralization of the MC3T3-E1 cells was visible using a von Kossa stain in the 5 J LLLT group. Osteogenic genes (Col-1, OC, OPG and BMP-2) were significantly expressed in the MC3T3-E1 cells treated with 5 J and 10 J LLLT (p < 0.05). LLLT in tension-cultured MC3T3-E1 cells showed synergistic osteogenic effects, including increases in cell proliferation and Col-1, OPN, OC, OPG and BMP-2 gene expression. LLLT might be beneficial for bone remodeling on the tension side of orthodontics.

  9. Mapping Human Cortical Areas in vivo Based on Myelin Content as Revealed by T1- and T2-weighted MRI

    PubMed Central

    Glasser, Matthew F.; Van Essen, David C.

    2011-01-01

    Non-invasively mapping the layout of cortical areas in humans is a continuing challenge for neuroscience. We present a new method of mapping cortical areas based on myelin content as revealed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The method is generalizable across different 3T scanners and pulse sequences. We use the ratio of T1w/T2w image intensities to eliminate the MR-related image intensity bias and enhance the contrast to noise ratio for myelin. Data from each subject was mapped to the cortical surface and aligned across individuals using surface-based registration. The spatial gradient of the group average myelin map provides an observer-independent measure of sharp transitions in myelin content across the surface—i.e. putative cortical areal borders. We found excellent agreement between the gradients of the myelin maps and the gradients of published probabilistic cytoarchitectonically defined cortical areas that were registered to the same surface-based atlas. For other cortical regions, we used published anatomical and functional information to make putative identifications of dozens of cortical areas or candidate areas. In general, primary and early unimodal association cortices are heavily myelinated and higher, multi-modal, association cortices are more lightly myelinated, but there are notable exceptions in the literature that are confirmed by our results. The overall pattern in the myelin maps also has important correlations with the developmental onset of subcortical white matter myelination, evolutionary cortical areal expansion in humans compared to macaques, postnatal cortical expansion in humans, and maps of neuronal density in non-human primates. PMID:21832190

  10. Identification of a 3rd Na+ Binding Site of the Glycine Transporter, GlyT2.

    PubMed

    Subramanian, Nandhitha; Scopelitti, Amanda J; Carland, Jane E; Ryan, Renae M; O'Mara, Megan L; Vandenberg, Robert J

    2016-01-01

    The Na+/Cl- dependent glycine transporters GlyT1 and GlyT2 regulate synaptic glycine concentrations. Glycine transport by GlyT2 is coupled to the co-transport of three Na+ ions, whereas transport by GlyT1 is coupled to the co-transport of only two Na+ ions. These differences in ion-flux coupling determine their respective concentrating capacities and have a direct bearing on their functional roles in synaptic transmission. The crystal structures of the closely related bacterial Na+-dependent leucine transporter, LeuTAa, and the Drosophila dopamine transporter, dDAT, have allowed prediction of two Na+ binding sites in GlyT2, but the physical location of the third Na+ site in GlyT2 is unknown. A bacterial betaine transporter, BetP, has also been crystallized and shows structural similarity to LeuTAa. Although betaine transport by BetP is coupled to the co-transport of two Na+ ions, the first Na+ site is not conserved between BetP and LeuTAa, the so called Na1' site. We hypothesized that the third Na+ binding site (Na3 site) of GlyT2 corresponds to the BetP Na1' binding site. To identify the Na3 binding site of GlyT2, we performed molecular dynamics (MD) simulations. Surprisingly, a Na+ placed at the location consistent with the Na1' site of BetP spontaneously dissociated from its initial location and bound instead to a novel Na3 site. Using a combination of MD simulations of a comparative model of GlyT2 together with an analysis of the functional properties of wild type and mutant GlyTs we have identified an electrostatically favorable novel third Na+ binding site in GlyT2 formed by Trp263 and Met276 in TM3, Ala481 in TM6 and Glu648 in TM10.

  11. Validation of a T1 and T2* leakage correction method based on multi-echo DSC-MRI using MION as a reference standard

    PubMed Central

    Stokes, Ashley M.; Semmineh, Natenael; Quarles, C. Chad

    2015-01-01

    Purpose A combined biophysical- and pharmacokinetic-based method is proposed to separate, quantify, and correct for both T1 and T2* leakage effects using dual-echo DSC acquisitions to provide more accurate hemodynamic measures, as validated by a reference intravascular contrast agent (CA). Methods Dual-echo DSC-MRI data were acquired in two rodent glioma models. The T1 leakage effects were removed and also quantified in order to subsequently correct for the remaining T2* leakage effects. Pharmacokinetic, biophysical, and combined biophysical and pharmacokinetic models were used to obtain corrected cerebral blood volume (CBV) and cerebral blood flow (CBF), and these were compared with CBV and CBF from an intravascular CA. Results T1-corrected CBV was significantly overestimated compared to MION CBV, while T1+T2*-correction yielded CBV values closer to the reference values. The pharmacokinetic and simplified biophysical methods showed similar results and underestimated CBV in tumors exhibiting strong T2* leakage effects. The combined method was effective for correcting T1 and T2* leakage effects across tumor types. Conclusions Correcting for both T1 and T2* leakage effects yielded more accurate measures of CBV. The combined correction method yields more reliable CBV measures than either correction method alone, but for certain brain tumor types (e.g., gliomas) the simplified biophysical method may provide a robust and computationally efficient alternative. PMID:26362714

  12. Role of postoperative radiation therapy (PORT) in pT1-T2 N0 deep tongue cancers.

    PubMed

    Gokavarapu, Sandhya; Parvataneni, Nagendra; Rao S, L M Chandrasekhara; Reddy, Rammohan; Raju, K V V N; Chander, Ravi

    2015-12-01

    Carcinoma of tongue is associated with a high risk of occult metastasis and mortality despite early-stage detection and therapy; the critical tumor thickness at which this risk increases has been demonstrated as 4 mm or greater. There are no sufficient data in the published literature to evaluate the role of postoperative radiation therapy (PORT) in the treatment of pT1-T2 N0 oral tongue cancers with depth of invasion 4 mm or greater. Historical cohorts of patients with primary pT1-T2 N0 oral tongue cancer of depth of invasion 4 mm or greater treated surgically from January 2010 to December 2012 were included in the study, and negative margins on initial resection were filtered. Locoregional recurrence and death were analyzed among the patients who received PORT and those who did not. A total of 103 patients fulfilled the above-mentioned criteria, with 62 patients receiving PORT and 41 patients not receiving PORT; median period of follow-up was 41.3 months. Logistic and Cox regression models showed no significant difference in locoregional recurrences (P = .078) and survival (P = .339) between patients who received PORT and those who did not receive PORT. PORT did not influence survival of patients with stage I and stage II deep tongue cancers, with 4 mm or greater tumor invasion depth. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The Non-Classical MAP Kinase ERK3 Controls T Cell Activation

    PubMed Central

    Mathien, Simon; Rousseau, Justine; Thébault, Paméla; Daudelin, Jean-François; Rooney, Julie; Turgeon, Benjamin; Beauchamp, Claudine; Meloche, Sylvain; Labrecque, Nathalie

    2014-01-01

    The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4+ and CD8+ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation. PMID:24475167

  14. Pharmacology and expression analysis of glycine transporter GlyT1 with [3H]-(N-[3-(4'-fluorophenyl)-3-(4'phenylphenoxy)propyl])sarcosine.

    PubMed

    Mallorga, Pierre J; Williams, Jacinta B; Jacobson, Marlene; Marques, Rosemary; Chaudhary, Ashok; Conn, P Jeffrey; Pettibone, Douglas J; Sur, Cyrille

    2003-10-01

    In the central nervous system, re-uptake of the neurotransmitter glycine is mediated by two different glycine transporters, GlyT1 and GlyT2. GlyT2 is found in brainstem and spinal cord, whereas GlyT1 is expressed in rat forebrain regions where it is responsible for most glycine transport activity. Initially, GlyT1 and GlyT2 were pharmacologically differentiated by sarcosine, a weak selective inhibitor of GlyT1. The recently described selective and potent GlyT1 antagonist, NFPS/ALX-5407 provided an important additional tool to further characterize GlyT1 pharmacology. In the present study, we have radiolabeled the racemic form of NFPS (N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (also known as ALX-5407) to investigate its interaction with GlyT1, as well as define GlyT1 expression in the rat central nervous system. Kinetic studies indicated that [3H]NFPS binds rapidly to rat forebrain membranes and dissociates with a t(1/2) of 28 +/- 5 min. [3H]NFPS labeled a saturable population of sites in rat forebrain with a Kd of 7.1+/-1.3 nM and a B(max) of 3.14 +/- 0.26 pmol/mg protein. Bound [3H]NFPS was fully and potently displaced by unlabeled NFPS, whereas glycine and sarcosine were weak, Na+-dependent inhibitors with IC50 of 1,008 and 190 microM, respectively. Additional saturation experiments indicated that glycine and sarcosine were non-competitive antagonists of [3H]NFPS binding. Functional studies revealed that NFPS was a non-competitive inhibitor of [3H]glycine uptake and does not interact with Na+ and Cl- binding sites of GlyT1. Overall, this work shows that [3H]NFPS is a valuable tool in studying GlyT1 expression and pharmacology and that NFPS interacts with GlyT1 at a site different from the transporter translocation and ion binding sites.

  15. Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells.

    PubMed

    Kojima, Itaru; Nakagawa, Yuko; Hamano, Kunihisa; Medina, Johan; Li, Longfei; Nagasawa, Masahiro

    2015-01-01

    Subunits of the sweet taste receptors T1R2 and T1R3 are expressed in pancreatic β-cells. Compared with T1R3, mRNA expression of T1R2 is considerably lower. At the protein level, expression of T1R2 is undetectable in β-cells. Accordingly, a major component of the sweet taste-sensing receptor in β-cells may be a homodimer of T1R3 rather than a heterodimer of T1R2/T1R3. Inhibition of this receptor by gurmarin or deletion of the T1R3 gene attenuates glucose-induced insulin secretion from β-cells. Hence the T1R3 homodimer functions as a glucose-sensing receptor (GSR) in pancreatic β-cells. When GSR is activated by the T1R3 agonist sucralose, elevation of intracellular ATP concentration ([ATP]i) is observed. Sucralose increases [ATP]i even in the absence of ambient glucose, indicating that sucralose increases [ATP]i not simply by activating glucokinase, a rate-limiting enzyme in the glycolytic pathway. In addition, sucralose augments elevation of [ATP]i induced by methylsuccinate, suggesting that sucralose activates mitochondrial metabolism. Nonmetabolizable 3-O-methylglucose also increases [ATP]i and knockdown of T1R3 attenuates elevation of [ATP]i induced by high concentration of glucose. Collectively, these results indicate that the T1R3 homodimer functions as a GSR; this receptor is involved in glucose-induced insulin secretion by activating glucose metabolism probably in mitochondria.

  16. Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel.

    PubMed

    Wang, Guangyu; Strang, Candace; Pfaffinger, Paul J; Covarrubias, Manuel

    2007-05-04

    The thiol-based redox regulation of proteins plays a central role in cellular signaling. Here, we investigated the redox regulation at the Zn(2+) binding site (HX(5)CX(20)CC) in the intracellular T1-T1 inter-subunit interface of a Kv4 channel. This site undergoes conformational changes coupled to voltage-dependent gating, which may be sensitive to oxidative stress. The main results show that internally applied nitric oxide (NO) inhibits channel activity profoundly. This inhibition is reversed by reduced glutathione and suppressed by intracellular Zn(2+), and at least two Zn(2+) site cysteines are required to observe the NO-induced inhibition (Cys-110 from one subunit and Cys-132 from the neighboring subunit). Biochemical evidence suggests strongly that NO induces a disulfide bridge between Cys-110 and Cys-132 in intact cells. Finally, further mutational studies suggest that intra-subunit Zn(2+) coordination involving His-104, Cys-131, and Cys-132 protects against the formation of the inhibitory disulfide bond. We propose that the interfacial T1 Zn(2+) site of Kv4 channels acts as a Zn(2+)-dependent redox switch that may regulate the activity of neuronal and cardiac A-type K(+) currents under physiological and pathological conditions.

  17. Organelle relationships in cultured 3T3-L1 preadipocytes

    PubMed Central

    1980-01-01

    In differentiating 3T3-L1 cells, lipid spheres, the endoplasmic reticulum (ER), microperoxisomes, and mitochondria form "constellations" that may reflect the interplay of lipid metabolizing enzymes in these organelles. ER cisternae are also situated very close to "rosettes,"plasmalemmal specializations found in mature adipocytes in vivo. As in hepatocytes and absorptive cells of the intestine, this spatial relationship of ER and plasmalemma suggests a role for rosettes in the uptake of exogenous lipid precursors. The morphological differentiation of 3T3-L1 preadipocytes includes the loss of "stress fibers" and the appearance of microfilament like structures that encase, in a complex manner, the cytosolic lipid spheres that appear during differentiation. Other features described for the first time in 3T3-L1 preadipocytes include: (a) the presence of an extensive acid phosphatase (AcPase) positive GERL from which coated vesicles apparently arise (these coated vesicles display AcPase activity and are much smaller and far more numerous than the coated vesicles that seem to arise from the plasmalemmal coated pits); (b) the abundance of AcPase-positive autophagic vacuoles; and (c) a high level of alpha- naphthyl-acetate-esterase activity which, by light microscopy cytochemistry, appears to be localized in the cytosol. PMID:7191426

  18. T Helper1/T Helper2 Cells and Resistance/Susceptibility to Leishmania Infection: Is This Paradigm Still Relevant?

    PubMed Central

    Alexander, James; Brombacher, Frank

    2012-01-01

    Work in large part on Leishmania major in the 1980s identified two distinct apparently counter-regulatory CD4+ T cell populations, T helper (h)1 and Th2, that controlled resistance/susceptibility to infection respectively. However, the generation of IL-4−/− mice in the 1990s questioned the paramount role of this Th2 archetypal cytokine in the non-healing response to Leishmania infection. The more recent characterization of CD4+ T cell regulatory populations and further effector CD4+ T helper populations, Th17, Th9, and T follicular (f)h cells as well as the acknowledged plasticity in T helper cell function has further added to the complexity of host pathogen interactions. These interactions are complicated by the multiplicity of cells that respond to CD4+ T cell subset signatory cytokines, as well as the diversity of Leishmania species that are often subject to significantly different immune-regulatory controls. In this article we review current knowledge with regard to the role of CD4+ T cells and their products during Leishmania infection. In particular we update on our studies using conditional IL-4Rα gene-deficient mice that have allowed dissection of the cell interplay dictating the disease outcomes of the major Leishmania species infecting humans. PMID:22566961

  19. PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis.

    PubMed

    Qiu, Ming-Ke; Wang, Song-Cun; Dai, Yu-Xin; Wang, Shu-Qing; Ou, Jing-Min; Quan, Zhi-Wei

    2015-01-01

    T cell-mediated immunity plays a significant role in the development of atherosclerosis (AS). There is increasing evidence that CD8+ T cells are also involved in AS but their exact roles remain unclear. The inhibitory receptors programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) are well known inhibitory molecules that play a crucial role in regulating CD8+ T cell activation or tolerance. Here, we demonstrate that the co-expression of PD-1 and Tim-3 on CD8+ T cells is up-regulated in AS patients. PD-1+ Tim-3+ CD8+ T cells are enriched for within the central T (TCM) cell subset, with high proliferative activity and CD127 expression. Co-expression of PD-1 and Tim-3 on CD8+ T cells is associated with increased anti-atherogenic cytokine production as well as decreased pro-atherogenic cytokine production. Blockade of PD-1 and Tim-3 results in a decrease of anti-atherogenic cytokine production by PD-1+ Tim-3+ CD8+ T cells and in an augmentation of TNF-α and IFN-γ production. These findings highlight the important role of the PD-1 and Tim-3 pathways in regulating CD8+ T cells function in human AS.

  20. PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis

    PubMed Central

    Qiu, Ming-Ke; Wang, Song-Cun; Dai, Yu-Xin; Wang, Shu-Qing; Ou, Jing-Min; Quan, Zhi-Wei

    2015-01-01

    T cell-mediated immunity plays a significant role in the development of atherosclerosis (AS). There is increasing evidence that CD8+ T cells are also involved in AS but their exact roles remain unclear. The inhibitory receptors programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) are well known inhibitory molecules that play a crucial role in regulating CD8+ T cell activation or tolerance. Here, we demonstrate that the co-expression of PD-1 and Tim-3 on CD8+ T cells is up-regulated in AS patients. PD-1+ Tim-3+ CD8+ T cells are enriched for within the central T (TCM) cell subset, with high proliferative activity and CD127 expression. Co-expression of PD-1 and Tim-3 on CD8+ T cells is associated with increased anti-atherogenic cytokine production as well as decreased pro-atherogenic cytokine production. Blockade of PD-1 and Tim-3 results in a decrease of anti-atherogenic cytokine production by PD-1+ Tim-3+ CD8+ T cells and in an augmentation of TNF-α and IFN-γ production. These findings highlight the important role of the PD-1 and Tim-3 pathways in regulating CD8+ T cells function in human AS. PMID:26035207

  1. Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing.

    PubMed

    Shirazi-Beechey, Soraya P; Daly, Kristian; Al-Rammahi, Miran; Moran, Andrew W; Bravo, David

    2014-06-01

    Luminal nutrient sensing by G-protein-coupled receptors (GPCR) expressed on the apical domain of enteroendocrine cells activates intracellular pathways leading to secretion of gut hormones that control vital physiological processes such as digestion, absorption, food intake and glucose homeostasis. The taste 1 receptor (T1R) family of GPCR consists of three members: T1R1; T1R2; T1R3. Expression of T1R1, T1R2 and T1R3 at mRNA and protein levels has been demonstrated in the intestinal tissue of various species. It has been shown that T1R2-T1R3, in association with G-protein gustducin, is expressed in intestinal K and L endocrine cells, where it acts as the intestinal glucose (sweet) sensor. A number of studies have demonstrated that activation of T1R2-T1R3 by natural sugars and artificial sweeteners leads to secretion of glucagon-like peptides 1&2 (GLP-1 and GLP-2) and glucose dependent insulinotropic peptide (GIP). GLP-1 and GIP enhance insulin secretion; GLP-2 increases intestinal growth and glucose absorption. T1R1-T1R3 combination co-expressed on the apical domain of cholecystokinin (CCK) expressing cells is a luminal sensor for a number of L-amino acids; with amino acid-activation of the receptor eliciting CCK secretion. This article focuses on the role of the gut-expressed T1R1, T1R2 and T1R3 in intestinal sweet and L-amino acid sensing. The impact of exploiting T1R2-T1R3 as a nutritional target for enhancing intestinal glucose absorption and gut structural maturity in young animals is also highlighted.

  2. Functional magnetic porous silica for T 1-T 2 dual-modal magnetic resonance imaging and pH-responsive drug delivery of basic drugs

    NASA Astrophysics Data System (ADS)

    Li, Ling; Zhang, Run; Guo, Yi; Zhang, Cheng; Zhao, Wei; Xu, Zhiping; Whittaker, Andrew K.

    2016-12-01

    A smart magnetic-targeting drug carrier γ-Fe2O3@p-silica comprising a γ-Fe2O3 core and porous shell has been prepared and characterized. The particles have a uniform size of about 60 nm, and a porous shell of thickness 3 nm. Abundant hydroxyl groups and a large surface area enabled the γ-Fe2O3@p-silica to be readily loaded with a large payload of the basic model drug rhodamine B (RB) (up to 73 mg g-1). Cytotoxicity assays of the γ-Fe2O3@p-silica particles indicated that the particles were biocompatible and suitable for carrying drugs. It was found that the RB was released rapidly at pH 5.5 but at pH 7.4 the rate and extent of release was greatly attenuated. The particles therefore demonstrate an excellent pH-triggered drug release. In addition, the γ-Fe2O3@p-silica particles could be tracked by magnetic resonance imaging (MRI). A clear dose-dependent contrast enhancement in both T 1-weighted and T 2-weighted MR images indicated the potential of the γ-Fe2O3@p-silica particles to act as dual-mode T 1 and T 2 MRI contrast agents.

  3. Salvage Surgery after Radiation Failure in T1/T2 Larynx Cancer: Outcomes following Total versus Conservation Surgery.

    PubMed

    Cheraghlou, Shayan; Kuo, Phoebe; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

    2018-03-01

    Objective After radiation failure for early T-stage larynx cancer, national guidelines recommend salvage surgery. Total laryngectomy and conservation laryngeal surgery with an open or endoscopic approach are both used. Beyond single-institution studies, there is a lack of evidence concerning the outcomes of these procedures. We aim to study whether treatment with conservation laryngeal surgery is associated with poorer outcomes than treatment with total laryngectomy as salvage surgery after radiation failure for T1/T2 larynx cancers. Study Design A retrospective study was conducted of adult squamous cell larynx cancer cases in the National Cancer Database diagnosed from 2004 to 2012. Setting Commission on Cancer cancer programs in the United States. Methods Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate survival regressions as well as univariate Kaplan-Meier analyses were conducted. Results Slightly more than 7% of patients receiving radiotherapy for T1/T2 larynx cancers later received salvage surgery. Salvage with partial laryngectomy was not associated with diminished survival as compared with total laryngectomy. However, positive surgical margins were associated with worse outcomes (hazard ratio, 1.782; P = .001), and a larger percentage of patients receiving partial laryngectomy had positive margins than those receiving total laryngectomy. Facility characteristics were not associated with differences in salvage surgery type or outcomes. Conclusion In recognition of the inherent selection bias, patients who experienced recurrences after radiation for T1/T2 larynx cancer and underwent conservation salvage laryngeal surgery demonstrated clinical outcomes similar to those of patients undergoing salvage total laryngectomy. Increased rates of positive surgical margins were observed among patients undergoing salvage conservation surgery.

  4. Detailed T1-Weighted Profiles from the Human Cortex Measured in Vivo at 3 Tesla MRI.

    PubMed

    Ferguson, Bart; Petridou, Natalia; Fracasso, Alessio; van den Heuvel, Martijn P; Brouwer, Rachel M; Hulshoff Pol, Hilleke E; Kahn, René S; Mandl, René C W

    2018-04-01

    Studies into cortical thickness in psychiatric diseases based on T1-weighted MRI frequently report on aberrations in the cerebral cortex. Due to limitations in image resolution for studies conducted at conventional MRI field strengths (e.g. 3 Tesla (T)) this information cannot be used to establish which of the cortical layers may be implicated. Here we propose a new analysis method that computes one high-resolution average cortical profile per brain region extracting myeloarchitectural information from T1-weighted MRI scans that are routinely acquired at a conventional field strength. To assess this new method, we acquired standard T1-weighted scans at 3 T and compared them with state-of-the-art ultra-high resolution T1-weighted scans optimised for intracortical myelin contrast acquired at 7 T. Average cortical profiles were computed for seven different brain regions. Besides a qualitative comparison between the 3 T scans, 7 T scans, and results from literature, we tested if the results from dynamic time warping-based clustering are similar for the cortical profiles computed from 7 T and 3 T data. In addition, we quantitatively compared cortical profiles computed for V1, V2 and V7 for both 7 T and 3 T data using a priori information on their relative myelin concentration. Although qualitative comparisons show that at an individual level average profiles computed for 7 T have more pronounced features than 3 T profiles the results from the quantitative analyses suggest that average cortical profiles computed from T1-weighted scans acquired at 3 T indeed contain myeloarchitectural information similar to profiles computed from the scans acquired at 7 T. The proposed method therefore provides a step forward to study cortical myeloarchitecture in vivo at conventional magnetic field strength both in health and disease.

  5. Esophageal carcinoma: Ex vivo evaluation by high-spatial-resolution T2 -mapping MRI compared with histopathological findings at 3.0T.

    PubMed

    Wei, Yi; Wu, Sen; Gao, Feifei; Sun, Tingyi; Zheng, Dandan; Ning, Peigang; Zhao, Cuihua; Li, Ziyuan; Li, Xiaodong; Li, Linlin; Zhu, Shaocheng

    2017-06-01

    To prospectively determine the feasibility of T 2 -mapping magnetic resonance imaging (MRI) to quantitatively describe the signal characteristics of the normal esophageal wall and assess the depth of esophageal wall invasion by carcinoma at 3.0T. Thirty-two patient specimens, each having foci of carcinoma, were studied using 3.0T MR. Freehand regions of interest were placed to measure the T 2 value of the normal esophageal layers and were compared with the regions of carcinoma. Three independent readers reviewed the MR images to evaluate the depth of carcinoma invasion; when the three radiologists could not fully agree with each other, the final stage was determined by consensus. The Games-Howell test was used to compare the difference between the normal esophageal layers and carcinoma. Spearman correlation coefficient analysis was used to compare the stage at MRI with that at histopathological analysis. The interobserver agreement was compared with Cohen's kappa. The sensitivity, specificity, and accuracy for detecting carcinoma invasion were calculated. The T 2 values between the carcinoma and normal esophageal layers were different (all P < 0.01), except for the inner circular muscle (P = 0.511). The T 2 value of each layer of the normal esophageal wall was also different from that of the adjacent layer (all P < 0.01). In 29 of 32 lesions, the depth of the esophageal wall invasion determined by MR was consistent with the histopathological stage (r = 0.969, P < 0.001). The sensitivity, specificity, and accuracy were 80%, 96.3%, and 93.8%, respectively, for invasion into the mucosa; 77.8%, 95.7%, and 90.6%, respectively, for invasion into submucosa; 100%, 95.8%, and 96.9%, respectively, for invasion into muscularis propria; and 100%, 100%, and 100%, respectively, for invasion into the adventitia. T 2 -mapping MR images obtained using a 3.0T MR scanner can be used to depict the precise histopathological layers of the esophageal wall clearly and provide

  6. Test-retest reliability and concurrent validity of in vivo myelin content indices: Myelin water fraction and calibrated T1 w/T2 w image ratio.

    PubMed

    Arshad, Muzamil; Stanley, Jeffrey A; Raz, Naftali

    2017-04-01

    In an age-heterogeneous sample of healthy adults, we examined test-retest reliability (with and without participant repositioning) of two popular MRI methods of estimating myelin content: modeling the short spin-spin (T 2 ) relaxation component of multi-echo imaging data and computing the ratio of T 1 -weighted and T 2 -weighted images (T 1 w/T 2 w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi-component T 2 relaxation data as a standard, we evaluate the concurrent and differential validity of T 1 w/T 2 w ratio images. The results revealed high reliability of MWF and T 1 w/T 2 w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T 1 w/T 2 w ratio in only two of six examined regions of the cerebral white matter. Notably, significant correlations of the same or greater magnitude were observed for T 1 w/T 2 w ratio and the intermediate T 2 relaxation time constant, which is believed to reflect differences in the mobility of water between the intracellular and extracellular compartments. We conclude that although both methods are highly reliable and thus well-suited for longitudinal studies, T 1 w/T 2 w ratio has low criterion validity and may be not an optimal index of subcortical myelin content. Hum Brain Mapp 38:1780-1790, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax.

    PubMed

    Higuchi, Masaya; Takahashi, Masahiko; Tanaka, Yuetsu; Fujii, Masahiro

    2014-12-01

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion-induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  8. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax

    PubMed Central

    Higuchi, Masaya; Takahashi, Masahiko; Tanaka, Yuetsu; Fujii, Masahiro

    2014-01-01

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion–induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo. PMID:25175936

  9. Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

    PubMed

    Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

    2018-05-01

    Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

  10. Divalent Metal Ions Induced Osteogenic Differentiation of MC3T3E1

    NASA Astrophysics Data System (ADS)

    Wang, Guoshou; Su, Wenta; Chen, Pohung; Huang, Teyang

    2017-12-01

    Biomaterial scaffolds blended with biochemical signal molecules with adequate osteoinductive and osteoconductive properties have attracted significant interest in bone tissue engineering regeneration. The divalent metal ions can gradually release from the scaffold into the culture medium and then induced osteoblastic differentiation of MC3T3E1. These MC3T3E1 cells expressed high activity of alkaline phosphatase, bone-related gene expression of collagen type I, Runx2, osteopontin, osteocalcin, and significantly enhanced deposited minerals on scaffold after 21 days of culture. This experiment provided a useful inducer for osteogenic differentiation in bone repair.

  11. Comparative analysis of T2 selective division of rami-communicantes (ramicotomy) with T2 sympathetic clipping in the treatment of craniofacial hyperhidrosis.

    PubMed

    Kim, Do Hyung; Paik, Hyo Chae; Lee, Doo Yun

    2004-08-01

    The main cause of dissatisfaction after sympathetic trunk blocking surgery (T2 sympathectomy, sympathetic clipping) for craniofacial hyperhidrosis is compensatory sweating. Preserving sympathetic trunk may decrease the incidence of compensatory sweating, and we introduce T2 ramicotomy, which may better preserve the sympathetic nerve trunk in order to reduce compensatory sweating. From January 2000 to November 2002, video-assisted thoracoscopic (VAT) T2 sympathetic clipping and VAT ramicotomy were performed in 44 patients suffering from craniofacial hyperhidrosis. Twenty-two patients underwent T2 sympathetic clipping (group 1), and 22 underwent division of T2 rami-communicantes (group 2). We retrospectively analyzed the rate of satisfaction, dryness of face, and grade of compensatory sweating. Both groups were similar with respect to facial dryness (P = 0.099). Group 1: excessive dry 5 patients (22.7%), dry 17 patients (77.3%); group 2: excessive dry 3 patients (13.6%), dry 15 patients (68.1%), and persistent sweating 4 patients (18.3%). The rate of satisfaction was 77.3% in group 1, and 63.6% in group 2 with no significant difference (P > 0.05). The rate of compensatory sweating in group 2 (72.7%) was significantly lower than in group 1 (95.4%) (P < 0.039). The chance of embarrassing and disabling compensatory sweating was lower in group 2 than in group 1; 76.5% (embarrassing in 8 patients, disabling in 9) in group 1, and 36.4% (embarrassing in 7 patients, disabling in 1) in group 2 which was statistically significant (P < 0.006). T2 ramicotomy for craniofacial hyperhidrosis lowers the rate of compensatory sweating and excessive dryness of face compared to T2 clipping.

  12. Effect of Preexisting Corrosion on Fatigue Cracking of Aluminum Alloys 2024-T3 and 7075-T6

    DTIC Science & Technology

    1995-08-01

    alloys 2024 -T3 and 7075-T6. It was determined that preexisting corrosion has a detrimental effect on the fatigue life of aluminum alloys 2024 -T3 and...following conclusions were drawn: 1. Preexisting corrosion has a detrimental effect on the fatigue life of aluminum alloys 2024 -T3 and 7075-T6. The...corrosion has a detrimental effect on the fatigue life of aluminum alloys

  13. Saturation pulse design for quantitative myocardial T1 mapping.

    PubMed

    Chow, Kelvin; Kellman, Peter; Spottiswoode, Bruce S; Nielles-Vallespin, Sonia; Arai, Andrew E; Salerno, Michael; Thompson, Richard B

    2015-10-01

    Quantitative saturation-recovery based T1 mapping sequences are less sensitive to systematic errors than the Modified Look-Locker Inversion recovery (MOLLI) technique but require high performance saturation pulses. We propose to optimize adiabatic and pulse train saturation pulses for quantitative T1 mapping to have <1 % absolute residual longitudinal magnetization (|MZ/M0|) over ranges of B0 and [Formula: see text] (B1 scale factor) inhomogeneity found at 1.5 T and 3 T. Design parameters for an adiabatic BIR4-90 pulse were optimized for improved performance within 1.5 T B0 (±120 Hz) and [Formula: see text] (0.7-1.0) ranges. Flip angles in hard pulse trains of 3-6 pulses were optimized for 1.5 T and 3 T, with consideration of T1 values, field inhomogeneities (B0 = ±240 Hz and [Formula: see text]=0.4-1.2 at 3 T), and maximum achievable B1 field strength. Residual MZ/M0 was simulated and measured experimentally for current standard and optimized saturation pulses in phantoms and in-vivo human studies. T1 maps were acquired at 3 T in human subjects and a swine using a SAturation recovery single-SHot Acquisition (SASHA) technique with a standard 90°-90°-90° and an optimized 6-pulse train. Measured residual MZ/M0 in phantoms had excellent agreement with simulations over a wide range of B0 and [Formula: see text]. The optimized BIR4-90 reduced the maximum residual |MZ/M0| to <1 %, a 5.8× reduction compared to a reference BIR4-90. An optimized 3-pulse train achieved a maximum residual |MZ/M0| <1 % for the 1.5 T optimization range compared to 11.3 % for a standard 90°-90°-90° pulse train, while a 6-pulse train met this target for the wider 3 T ranges of B0 and [Formula: see text]. The 6-pulse train demonstrated more uniform saturation across both the myocardium and entire field of view than other saturation pulses in human studies. T1 maps were more spatially homogeneous with 6-pulse train SASHA than the reference 90°-90°-90° SASHA in both

  14. Absence of PDGF-induced, PKC-independent c-fos expression in a chemically transformed C3H/10T1/2 cell clone.

    PubMed

    Vassbotn, F S; Skar, R; Holmsen, H; Lillehaug, J R

    1992-09-01

    The effect of platelet-derived growth factor (PDGF) on c-fos mRNA transcription was studied in the immortalized mouse embryo fibroblast C3H/10T1/2 Cl 8 (10T1/2) cells and the chemically transformed, tumorigenic subclone C3H/10T1/2 Cl 16 (Cl 16). In the 10T1/2 cells as well as the Cl 16 subclone, the dose-dependent PDGF stimulation of c-fos mRNA synthesis was similar in both logarithmically growing and confluent cultures. c-fos mRNA was induced severalfold by 12-O-tetradecanoylphorbol-13-acetate (TPA) in both 10T1/2 and Cl 16. Down-regulation of protein kinase C (PKC) activity by TPA pretreatment inhibited PDGF-stimulated c-fos mRNA expression in Cl 16 cells but did not affect this induction in the 10T1/2 cells. This inhibition was not a general phenomenon of 3-methylcholanthrene-mediated transformation of 10T1/2 cells since experiments with another transformed 10T1/2 cell clone, C3H/10T1/2 TPA 482, gave qualitatively the same results as the 10T1/2 cells. Receptor binding experiments showed that the nontransformed and transformed cells had a comparable number of PDGF receptors, 1.3 x 10(5) and 0.7 x 10(5) receptors per cell, respectively. Furthermore, cAMP-induced c-fos expression induced by forskolin is formerly shown to be independent of PKC down-regulation. In our experiments, forskolin induced c-fos expression in both clones. However, PKC down-regulation inhibited the forskolin-induced c-fos expression in Cl 16 cells. This apparently demonstrates cross talk between PKC and PKA in the c-fos induction pathway. The present results provide evidence for an impaired mechanism for activating c-fos expression through PKC-independent, PDGF-induced signal transduction in the chemically transformed Cl 16 fibroblasts compared to that in nontransformed 10T1/2 cells.

  15. Proton range shift analysis on brain pseudo-CT generated from T1 and T2 MR.

    PubMed

    Pileggi, Giampaolo; Speier, Christoph; Sharp, Gregory C; Izquierdo Garcia, David; Catana, Ciprian; Pursley, Jennifer; Amato, Francesco; Seco, Joao; Spadea, Maria Francesca

    2018-05-29

    In radiotherapy, MR imaging is only used because it has significantly better soft tissue contrast than CT, but it lacks electron density information needed for dose calculation. This work assesses the feasibility of using pseudo-CT (pCT) generated from T1w/T2w MR for proton treatment planning, where proton range comparisons are performed between standard CT and pCT. MR and CT data from 14 glioblastoma patients were used in this study. The pCT was generated by using conversion libraries obtained from tissue segmentation and anatomical regioning of the T1w/T2w MR. For each patient, a plan consisting of three 18 Gy beams was designed on the pCT, for a total of 42 analyzed beams. The plan was then transferred onto the CT that represented the ground truth. Range shift (RS) between pCT and CT was computed at R 80 over 10 slices. The acceptance threshold for RS was according to clinical guidelines of two institutions. A γ-index test was also performed on the total dose for each patient. Mean absolute error and bias for the pCT were 124 ± 10 and -16 ± 26 Hounsfield Units (HU), respectively. The median and interquartile range of RS was 0.5 and 1.4 mm, with highest absolute value being 4.4 mm. Of the 42 beams, 40 showed RS less than the clinical range margin. The two beams with larger RS were both in the cranio-caudal direction and had segmentation errors due to the partial volume effect, leading to misassignment of the HU. This study showed the feasibility of using T1w and T2w MRI to generate a pCT for proton therapy treatment, thus avoiding the use of a planning CT and allowing better target definition and possibilities for online adaptive therapies. Further improvements of the methodology are still required to improve the conversion from MRI intensities to HUs.

  16. Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3+ regulatory T cells

    PubMed Central

    Vaeth, Martin; Schliesser, Ulrike; Müller, Gerd; Reissig, Sonja; Satoh, Kazuki; Tuettenberg, Andrea; Jonuleit, Helmut; Waisman, Ari; Müller, Martin R.; Serfling, Edgar; Sawitzki, Birgit S.; Berberich-Siebelt, Friederike

    2012-01-01

    Several lines of evidence suggest nuclear factor of activated T-cells (NFAT) to control regulatory T cells: thymus-derived naturally occurring regulatory T cells (nTreg) depend on calcium signals, the Foxp3 gene harbors several NFAT binding sites, and the Foxp3 (Fork head box P3) protein interacts with NFAT. Therefore, we investigated the impact of NFAT on Foxp3 expression. Indeed, the generation of peripherally induced Treg (iTreg) by TGF-β was highly dependent on NFAT expression because the ability of CD4+ T cells to differentiate into iTreg diminished markedly with the number of NFAT family members missing. It can be concluded that the expression of Foxp3 in TGF-β–induced iTreg depends on the threshold value of NFAT rather than on an individual member present. This is specific for iTreg development, because frequency of nTreg remained unaltered in mice lacking NFAT1, NFAT2, or NFAT4 alone or in combination. Different from expectation, however, the function of both nTreg and iTreg was independent on robust NFAT levels, reflected by less nuclear NFAT in nTreg and iTreg. Accordingly, absence of one or two NFAT members did not alter suppressor activity in vitro or during colitis and transplantation in vivo. This scenario emphasizes an inhibition of high NFAT activity as treatment for autoimmune diseases and in transplantation, selectively targeting the proinflammatory conventional T cells, while keeping Treg functional. PMID:22991461

  17. Transcription factor Sp1 regulates T-type Ca(2+) channel CaV 3.1 gene expression.

    PubMed

    González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Felix, Ricardo

    2014-05-01

    Voltage-gated T-type Ca(2+) (CaV 3) channels mediate a number of physiological events in developing and mature cells, and are implicated in neurological and cardiovascular diseases. In mammals, there are three distinct T-channel genes (CACNA1G, CACNA1H, and CACNA1I) encoding proteins (CaV 3.1-CaV 3.3) that differ in their localization as well as in molecular, biophysical, and pharmacological properties. The CACNA1G is a large gene that contains 38 exons and is localized in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter region have been investigated classifying it as a TATA-less sequence containing several potential transcription factor-binding motifs. Here, we cloned and characterized a proximal promoter region and initiated the analysis of transcription factors that control CaV 3.1 channel expression using the murine Cacna1g gene as a model. We isolated a ∼1.5 kb 5'-upstream region of Cacna1g and verified its transcriptional activity in the mouse neuroblastoma N1E-115 cell line. In silico analysis revealed that this region possesses a TATA-less minimal promoter that includes two potential transcription start sites and four binding sites for the transcription factor Sp1. The ability of one of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. © 2013 Wiley Periodicals, Inc.

  18. The Importance of the Presence of a 5′-Ribonucleotide and the Contribution of the T1R1 + T1R3 Heterodimer and an Additional Low-Affinity Receptor in the Taste Detection of l-Glutamate as Assessed Psychophysically

    PubMed Central

    Smith, Kimberly R.

    2014-01-01

    The molecular receptors underlying the purported “umami” taste quality commonly associated with l-glutamate have been controversial. Evidence supports the involvement of the T1R1 + T1R3 heterodimer, a GPCR broadly tuned to l-amino acids, but variants of two mGluRs expressed in taste buds have also been implicated. Using a rigorous psychophysical taste-testing paradigm, we demonstrated impaired, if not eliminated, detection of MSG in WT and T1R1, T1R2, T1R3, and T1R2 + T1R3 KO mice when the contribution of sodium was minimized by the epithelial sodium channel blocker amiloride. When inosine 5′-monophosphate (IMP), a ribonucleotide that potentiates the l-glutamate signal through the T1R1 + T1R3 heterodimer, was added, the WT and T1R2 KO mice were able to detect the compound stimulus across all MSG (+amiloride) concentrations due, in part, to the taste of IMP. In contrast, mice lacking T1R1 or T1R3 could not detect IMP alone, yet some were able to detect MSG + amiloride + IMP, but only at the higher MSG concentrations. Interestingly, the sensitivity of T1R1 KO mice to another l-amino acid, lysine, was unimpaired, suggesting that some l-amino acids can be detected through T1R1 + T1R3-independent receptors without sensitivity loss. Given that IMP is not thought to affect mGluRs, behavioral detection of l-glutamate appears to require the contribution of the T1R1 + T1R3 receptor. However, the partial competence observed in some T1R1 and T1R3 KO mice when MSG + amiloride + IMP was tested suggests that a T1R1 or T1R3 homodimer or an unidentified protein, perhaps in conjunction with T1R1 or T1R3, can serve as a low-affinity taste receptor for l-glutamate in the presence of IMP. PMID:25253867

  19. Imprints of a light sterile neutrino at DUNE, T2HK, and T2HKK

    NASA Astrophysics Data System (ADS)

    Choubey, Sandhya; Dutta, Debajyoti; Pramanik, Dipyaman

    2017-09-01

    We evaluate the impact of sterile neutrino oscillations in the so-called 3 +1 scenario on the proposed long baseline experiment in USA and Japan. There are two proposals for the Japan experiment which are called T2HK and T2HKK. We show the impact of sterile neutrino oscillation parameters on the expected sensitivity of T2HK and T2HKK to mass hierarchy, C P violation and octant of θ23 and compare it against that expected in the case of standard oscillations. We add the expected ten years data from DUNE and present the combined expected sensitivity of T 2 HKK +DUNE to the oscillation parameters. We do a full marginalization over the relevant parameter space and show the effect of the magnitude of the true sterile mixing angles on the physics reach of these experiments. We show that if one assumes that the source of C P violation is the standard C P phase alone in the test case, then it appears that the expected C P violation sensitivity decreases due to sterile neutrinos. However, if we give up this assumption, then the C P sensitivity could go in either direction. The impact on expected octant of θ23 and mass hierarchy sensitivity is shown to depend on the magnitude of the sterile mixing angles in a nontrivial way.

  20. Usefulness of IDEAL T2 imaging for homogeneous fat suppression and reducing susceptibility artefacts in brachial plexus MRI at 3.0 T.

    PubMed

    Tagliafico, Alberto; Bignotti, Bianca; Tagliafico, Giulio; Martinoli, Carlo

    2016-01-01

    To quantitatively and qualitatively compare fat-suppressed MR imaging quality using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with that using frequency-selective fat-suppressed (FSFS) T2 images of the brachial plexus at 3.0 T. Prospective MR image analysis was performed in 40 volunteers and 40 patients at a single centre. Oblique-sagittal and coronal IDEAL fat-suppressed T2 images and FSFS T2 images were compared. Visual assessment was performed by two independent musculoskeletal radiologists with respect to: (1) susceptibility artefacts around the neck, (2) homogeneity of fat suppression, (3) image sharpness and (4) tissue resolution contrast of pathologies. The signal-to-noise ratios (SNR) for each image sequence were assessed. Compared to FSFS sequences, IDEAL fat-suppressed T2 images significantly reduced artefacts around the brachial plexus and significantly improved homogeneous fat suppression (p < 0.05). IDEAL significantly improved sharpness and lesion-to-tissue contrast (p < 0.05). The mean SNRs were significantly improved on T2-weighted IDEAL images (p < 0.05). IDEAL technique improved image quality by reducing artefacts around the brachial plexus while maintaining a high SNR and provided superior homogeneous fat suppression than FSFS sequences.

  1. RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

    PubMed

    Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

    2015-12-01

    26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314566221, first published on February 1, 2015 doi: 10.1177/1470320314566221 Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang, and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population Journal of Renin-Angiotensin-Aldosterone System March 2015 16: 165-171, first published on November 14, 2014 doi: 10.1177/1470320314557849 Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang, and Tian-Biao Zhou Association of aldosterone synthase (CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy Journal of Renin-Angiotensin-Aldosterone System September 2015 16: 660-665, first published on August 20, 2014 doi: 10.1177/1470320314524011.

  2. The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications.

    PubMed

    Dewe, Joshua M; Whipple, Joseph M; Chernyakov, Irina; Jaramillo, Laura N; Phizicky, Eric M

    2012-10-01

    The structural and functional integrity of tRNA is crucial for translation. In the yeast Saccharomyces cerevisiae, certain aberrant pre-tRNA species are subject to nuclear surveillance, leading to 3' exonucleolytic degradation, and certain mature tRNA species are subject to rapid tRNA decay (RTD) if they are appropriately hypomodified or bear specific destabilizing mutations, leading to 5'-3' exonucleolytic degradation by Rat1 and Xrn1. Thus, trm8-Δ trm4-Δ strains are temperature sensitive due to lack of m(7)G(46) and m(5)C and the consequent RTD of tRNA(Val(AAC)), and tan1-Δ trm44-Δ strains are temperature sensitive due to lack of ac(4)C(12) and Um(44) and the consequent RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)). It is unknown how the RTD pathway interacts with translation and other cellular processes, and how generally this pathway acts on hypomodified tRNAs. We provide evidence here that elongation factor 1A (EF-1A) competes with the RTD pathway for substrate tRNAs, since its overexpression suppresses the tRNA degradation and the growth defect of strains subject to RTD, whereas reduced levels of EF-1A have the opposite effect. We also provide evidence that RTD acts on a variety of tRNAs lacking one or more different modifications, since trm1-Δ trm4-Δ mutants are subject to RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)) due to lack of m(2,2)G(26) and m(5)C, and since trm8-Δ, tan1-Δ, and trm1-Δ single mutants are each subject to RTD. These results demonstrate that RTD interacts with the translation machinery and acts widely on hypomodified tRNAs.

  3. The non-classical MAP kinase ERK3 controls T cell activation.

    PubMed

    Marquis, Miriam; Boulet, Salix; Mathien, Simon; Rousseau, Justine; Thébault, Paméla; Daudelin, Jean-François; Rooney, Julie; Turgeon, Benjamin; Beauchamp, Claudine; Meloche, Sylvain; Labrecque, Nathalie

    2014-01-01

    The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4⁺ and CD8⁺ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation.

  4. T cell fates ‘zipped up’: how the Bach2 basic leucine zipper transcriptional repressor directs T cell differentiation and function1

    PubMed Central

    Richer, Martin J.; Lang, Mark L.; Butler, Noah S.

    2016-01-01

    Recent data illustrate a key role for the transcriptional regulator Bach2 in orchestrating T cell differentiation and function. Although Bach2 has a well-described role in B cell differentiation, emerging data show that Bach2 is a prototypical member of a novel class of transcription factors that regulates transcriptional activity in T cells at super enhancers, or regions of high transcriptional activity. Accumulating data demonstrate specific roles for Bach2 in favoring regulatory T cell generation, restraining effector T cell differentiation and potentiating memory T cell development. Evidence suggests that Bach2 regulates various facets of T cell function by repressing other key transcriptional regulator such as Blimp-1. This review examines our current understanding of the role of Bach2 in T cell function and highlights the growing evidence that this transcriptional repressor functions as a key regulator involved in maintenance of T cell quiescence, T cell subset differentiation and memory T cell generation. PMID:27496973

  5. CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells.

    PubMed

    Mudado, M A; Rodrigues, A L; Prado, V F; Beirão, P S L; Cruz, J S

    2004-06-01

    T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 +/- 1.87 ms (N = 16). The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 +/- 2.4 and 6.7 +/- 0.3 mV (pre-pulse of -120 mV, N = 15), and -27.0 +/- 0.97 and 7.5 +/- 0.7 mV (pre-pulse of -40 mV, N = 9). The 8-mV shift in the activation mid-point was statistically significant (P < 0.05). The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of alpha1G (CaV3.1) and alpha1I (CaV3.3) T-type Ca2+ channel mRNA transcripts.

  6. Ability of γδ T cells to modulate the Foxp3 T cell response is dependent on adenosine.

    PubMed

    Liang, Dongchun; Woo, Jeong-Im; Shao, Hui; Born, Willi K; O'Brien, Rebecca L; Kaplan, Henry J; Sun, Deming

    2018-01-01

    Whether γδ T cells inhibit or enhance the Foxp3 T cell response depends upon their activation status. The critical enhancing effector in the supernatant is adenosine. Activated γδ T cells express adenosine receptors at high levels, which enables them to deprive Foxp3+ T cells of adenosine, and to inhibit their expansion. Meanwhile, cell-free supernatants of γδ T cell cultures enhance Foxp3 T cell expansion. Thus, inhibition and enhancement by γδ T cells of Foxp3 T cell response are a reflection of the balance between adenosine production and absorption by γδ T cells. Non-activated γδ T cells produce adenosine but bind little, and thus enhance the Foxp3 T cell response. Activated γδ T cells express high density of adenosine receptors and have a greatly increased ability to bind adenosine. Extracellular adenosine metabolism and expression of adenosine receptor A2ARs by γδ T cells played a major role in the outcome of γδ and Foxp3 T cell interactions. A better understanding of the functional conversion of γδ T cells could lead to γδ T cell-targeted immunotherapies for related diseases.

  7. Feasibility of imaging superficial palmar arch using micro-ultrasound, 7T and 3T magnetic resonance imaging.

    PubMed

    Pruzan, Alison N; Kaufman, Audrey E; Calcagno, Claudia; Zhou, Yu; Fayad, Zahi A; Mani, Venkatesh

    2017-02-28

    To demonstrate feasibility of vessel wall imaging of the superficial palmar arch using high frequency micro-ultrasound, 7T and 3T magnetic resonance imaging (MRI). Four subjects (ages 22-50 years) were scanned on a micro-ultrasound system with a 45-MHz transducer (Vevo 2100, VisualSonics). Subjects' hands were then imaged on a 3T clinical MR scanner (Siemens Biograph MMR) using an 8-channel special purpose phased array carotid coil. Lastly, subjects' hands were imaged on a 7T clinical MR scanner (Siemens Magnetom 7T Whole Body Scanner) using a custom built 8-channel transmit receive carotid coil. All three imaging modalities were subjectively analyzed for image quality and visualization of the vessel wall. Results of this very preliminary study indicated that vessel wall imaging of the superficial palmar arch was feasible with a whole body 7T and 3T MRI in comparison with micro-ultrasound. Subjective analysis of image quality (1-5 scale, 1: poorest, 5: best) from B mode, ultrasound, 3T SPACE MRI and 7T SPACE MRI indicated that the image quality obtained at 7T was superior to both 3T MRI and micro-ultrasound. The 3D SPACE sequence at both 7T and 3T MRI with isotropic voxels allowed for multi-planar reformatting of images and allowed for less operator dependent results as compared to high frequency micro-ultrasound imaging. Although quantitative analysis revealed that there was no significant difference between the three methods, the 7T Tesla trended to have better visibility of the vessel and its wall. Imaging of smaller arteries at the 7T is feasible for evaluating atherosclerosis burden and may be of clinical relevance in multiple diseases.

  8. Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A(T1)C1-3 cells by cancer chemotherapeutic agents.

    PubMed

    Benedict, W F; Banerjee, A; Gardner, A; Jones, P A

    1977-07-01

    Various cancer chemotherapeutic agents including alkylating agents, antimetabolites, and antibiotics or natural products were studied for their ability to produce morphological transformation in the C3H/10T1/2 clone 8 mouse cell line and chromosomal damage in the A(T1)C1-3 hamster cell line following a 24-hr exposure of each agent at different concentrations. Those drugs that were known to be carcinogenic in vivo also produced morphological transformation and chromosomal damage, whereas those agents that have not been shown to be carcinogenic in vivo produced neither transformation nor chromosomal lesions. The concentrations used for these studies were in general similar to those actually reached in the plasma of patients treated with these same drugs for malignant, as well as certain nonmalignant, conditions.

  9. t-BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO-1 Pathway

    PubMed Central

    Ye, Fang; Li, Xiaoyi; Li, Lili; Yuan, Jing; Chen, Jun

    2016-01-01

    The neurotoxicity of lead has been well established, and oxidative stress is strongly associated with lead-induced neurotoxicity. Nrf2 is important for protection against oxidative stress in many disease models. We applied t-BHQ, which is an Nrf2 activator, to investigate the possible role of Nrf2 in the protection against lead neurotoxicity. t-BHQ significantly attenuated the oxidative stress in developmental rats by decreasing MDA level, as well as by increasing SOD activity and GSH content, in the hippocampus and frontal cortex. Furthermore, neuronal apoptosis was detected by Nissl staining, and Bax expression was inhibited in the t-BHQ-treated group. Results showed that t-BHQ suppressed ROS production and caspase 3/7 activity but increased intracellular GSH content, in SH-SY5Y cells under lead exposure. Moreover, in vivo and in vitro, t-BHQ enhanced the nuclear translocation of Nrf2 and binding to ARE areas but did not induce Nrf2 transcription. These phenomena were confirmed using RT-PCR, EMSA, Western blot, and immunofluorescence analyses. Subsequent upregulation of the expression of HO-1, NQO1, and GCLC was observed. However, knockdown of Nrf2 or HO-1 adversely affected the protective effects of t-BHQ against lead toxicity in SH-SY5Y cells. Thus, t-BHQ can protect against lead neurotoxicity, depending on the Nrf2/HO-1 pathway. PMID:26798413

  10. A T3 and T7 Recombinant Phage Acquires Efficient Adsorption and a Broader Host Range

    PubMed Central

    Lin, Tiao-Yin; Lo, Yi-Haw; Tseng, Pin-Wei; Chang, Shun-Fu; Lin, Yann-Tsyr; Chen, Ton-Seng

    2012-01-01

    It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress. PMID:22347414

  11. A T3 and T7 recombinant phage acquires efficient adsorption and a broader host range.

    PubMed

    Lin, Tiao-Yin; Lo, Yi-Haw; Tseng, Pin-Wei; Chang, Shun-Fu; Lin, Yann-Tsyr; Chen, Ton-Seng

    2012-01-01

    It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress.

  12. Human Follicular Lymphoma CD39+-Infiltrating T Cells Contribute to Adenosine-Mediated T Cell Hyporesponsiveness1

    PubMed Central

    Hilchey, Shannon P.; Kobie, James J.; Cochran, Mathew R.; Secor-Socha, Shelley; Wang, Jyh-Chiang E.; Hyrien, Ollivier; Burack, W. Richard; Mosmann, Tim R.; Quataert, Sally A.; Bernstein, Steven H.

    2010-01-01

    Our previous work has demonstrated that human follicular lymphoma (FL) infiltrating T cells are anergic, in part due to suppression by regulatory T cells. In this study, we identify pericellular adenosine, interacting with T cell-associated G protein-coupled A2A/B adenosine receptors (AR), as contributing to FL T cell hyporesponsiveness. In a subset of FL patient samples, treatment of lymph node mononuclear cells (LNMC) with specific A2A/B AR antagonists results in an increase in IFN-γ or IL-2 secretion upon anti-CD3/CD28 Ab stimulation, as compared with that seen without inhibitors. In contrast, treatment with an A1 AR antagonist had no effect on cytokine secretion. As the rate limiting step for adenosine generation from pericellular ATP is the ecto-ATPase CD39, we next show that inhibition of CD39 activity using the inhibitor ARL 67156 partially overcomes T cell hyporesponsiveness in a subset of patient samples. Phenotypic characterization of LNMC demonstrates populations of CD39-expressing CD4+ and CD8+ T cells, which are overrepresented in FL as compared with that seen in normal or reactive nodes, or normal peripheral blood. Thirty percent of the FL CD4+CD39+ T cells coexpress CD25high and FOXP3 (consistent with regulatory T cells). Finally, FL or normal LNMC hydrolyze ATP in vitro, in a dose- and time-dependent fashion, with the rate of ATP consumption being associated with the degree of CD39+ T cell infiltration. Together, these results support the finding that the ATP-ectonucleotidase-adenosine system mediates T cell anergy in a human tumor. In addition, these studies suggest that the A2A/B AR as well as CD39 are novel pharmacological targets for augmenting cancer immunotherapy. PMID:19864600

  13. C2C12 myotubes inhibit the proliferation and differentiation of 3T3-L1 preadipocytes by reducing the expression of glucocorticoid receptor gene

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chu, Weiwei; Wei, Wei; Yu, Shigang

    Obesity is a well-established risk factor to health for its relationship with insulin resistance, diabetes and metabolic syndrome. Myocyte-adipocyte crosstalk model plays a significant role in studying the interaction of muscle and adipose development. Previous related studies mainly focus on the effects of adipocytes on the myocytes activity, however, the influence of myotubes on the preadipocytes development remains unclear. The present study was carried out to settle this issue. Firstly, the co-culture experiment showed that the proliferation, cell cycle, and differentiation of 3T3-L1 preadipocytes were arrested, and the apoptosis was induced, by differentiated C2C12 myotubes. Next, the sensitivity of 3T3-L1more » preadipocytes to glucocorticoids (GCs), which was well known as cell proliferation, differentiation, apoptosis factor, was decreased after co-cultured with C2C12 myotubes. What's more, our results showed that C2C12 myotubes suppressed the mRNA and protein expression of glucocorticoid receptor (GR) in 3T3-L1 preadipocytes, indicating the potential mechanism of GCs sensitivity reduction. Taken together, we conclude that C2C12 myotubes inhibited 3T3-L1 preadipocytes proliferation and differentiation by reducing the expression of GR. These data suggest that decreasing GR by administration of myokines may be a promising therapy for treating patients with obesity or diabetes. - Highlights: • C2C12 myotubes inhibited proliferation and differentiation of 3T3-L1 preadipocytes. • C2C12 myotubes arrested cell cycle of 3T3-L1 preadipocytes. • C2C12 myotubes induced apoptosis of 3T3-L1 preadipocytes. • C2C12 inhibit 3T3-L1 cells by reducing the expression of glucocorticoid receptor gene.« less

  14. Capacity for cooperative binding of thyroid hormone (T3) receptor dimers defines wild type T3 response elements.

    PubMed

    Brent, G A; Williams, G R; Harney, J W; Forman, B M; Samuels, H H; Moore, D D; Larsen, P R

    1992-04-01

    Thyroid hormone response elements (T3REs) have been identified in a variety of promoters including those directing expression of rat GH (rGH), alpha-myosin heavy chain (rMHC), and malic enzyme (rME). A detailed biochemical and genetic analysis of the rGH element has shown that it consists of three hexamers related to the consensus [(A/G)GGT(C/A)A]. We have extended this analysis to the rMHC and rME elements. Binding of highly purified thyroid hormone receptor (T3R) to T3REs was determined using the gel shift assay, and thyroid hormone (T3) induction was measured in transient tranfections. We show that the wild type version of each of the three elements binds T3R dimers cooperatively. Mutational analysis of the rMHC and rME elements identified domains important for binding T3R dimers and allowed a direct determination of the relationship between T3R binding and function. In each element two hexamers are required for dimer binding, and mutations that interfere with dimer formation significantly reduce T3 induction. Similar to the rGH element, the rMHC T3RE contains three hexameric domains arranged as a direct repeat followed by an inverted copy, although the third domain is weaker than in rGH. All three are required for full function and T3R binding. The rME T3RE is a two-hexamer direct repeat T3RE, which also binds T3R monomer and dimer. Across a series of mutant elements, there was a strong correlation between dimer binding in vitro and function in vivo for rMHC (r = 0.99, P less than 0.01) and rME (r = 0.67, P less than 0.05) T3REs. Our results demonstrate a similar pattern of T3R dimer binding to a diverse array of hexameric sequences and arrangements in three wild type T3REs. Addition of nuclear protein enhanced T3R binding but did not alter the specificity of binding to wild type or mutant elements. Binding of purified T3R to T3REs was highly correlated with function, both with and without the addition of nuclear protein. T3R dimer formation is the common

  15. Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach

    NASA Astrophysics Data System (ADS)

    Wang, Chuang; Udupa, Jayaram K.; Tong, Yubing; Chen, Jerry; Venigalla, Sriram; Odhner, Dewey; Guzzo, Thomas J.; Christodouleas, John; Torigian, Drew A.

    2018-02-01

    Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 - T stage < T2, with primary tumor locally confined to the bladder, and group 2 - T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

  16. Facile preparation of multifunctional uniform magnetic microspheres for T1-T2 dual modal magnetic resonance and optical imaging.

    PubMed

    Zhang, Li; Liang, Shuang; Liu, Ruiqing; Yuan, Tianmeng; Zhang, Shulai; Xu, Zushun; Xu, Haibo

    2016-08-01

    Molecular imaging is of significant importance for early detection and diagnosis of cancer. Herein, a novel core-shell magnetic microsphere for dual modal magnetic resonance imaging (MRI) and optical imaging was produced by one-pot emulsifier-free emulsion polymerization, which could provide high resolution rate of histologic structure information and realize high sensitive detection at the same time. The synthesized magnetic microspheres composed of cores containing oleic acid (OA) and sodium undecylenate (NaUA) modified Fe3O4 nanoparticles and styrene (St), Glycidyl methacrylate (GMA), and polymerizable lanthanide complexes (Gd(AA)3Phen and Eu(AA)3Phen) polymerized on the surface for outer shells. Fluorescence spectra show characteristic emission peaks from Eu(3+) at 590nm and 615nm and vivid red fluorescence luminescence can be observed by 2-photon confocal scanning laser microscopy (CLSM). In vitro cytotoxicity tests based on the MTT assay demonstrate good cytocompatibility, the composites have longitudinal relaxivity value (r1) of 8.39mM(-1)s(-1) and also have transverse relaxivity value (r2) of 71.18mM(-1)s(-1) at clinical 3.0 T MR scanner. In vitro and in vivo MRI studies exhibit high signal enhancement on both T1- and T2-weighted MR images. These fascinating multifunctional properties suggest that the polymer microspheres have large clinical potential as multi-modal MRI/optical probes. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  17. Reliability of MRSI brain temperature mapping at 1.5 and 3 T.

    PubMed

    Thrippleton, Michael J; Parikh, Jehill; Harris, Bridget A; Hammer, Steven J; Semple, Scott I K; Andrews, Peter J D; Wardlaw, Joanna M; Marshall, Ian

    2014-02-01

    MRSI permits the non-invasive mapping of brain temperature in vivo, but information regarding its reliability is lacking. We obtained MRSI data from 31 healthy male volunteers [age range, 22-40 years; mean ± standard deviation (SD), 30.5 ± 5.0 years]. Eleven subjects (age range, 23-40 years; mean ± SD, 30.5 ± 5.2 years) were invited to receive four point-resolved spectroscopy MRSI scans on each of 3 days in both 1.5-T (TR/TE = 1000/144 ms) and 3-T (TR/TE = 1700/144 ms) clinical scanners; a further 20 subjects (age range, 22-40 years; mean ± SD, 30.5 ± 4.9 years) were scanned on a single occasion at 3 T. Data were fitted in the time domain to determine the water-N-acetylaspartate chemical shift difference, from which the temperature was estimated. Temperature data were analysed using a linear mixed effects model to determine variance components and systematic temperature changes during the scanning sessions. To characterise the effects of instrumental drift on apparent MRSI brain temperature, a temperature-controlled phantom was constructed and scanned on multiple occasions. Components of apparent in vivo temperature variability at 1.5 T/3 T caused by inter-subject (0.18/0.17 °C), inter-session (0.18/0.15 °C) and within-session (0.36/0.14 °C) effects, as well as voxel-to-voxel variation (0.59/0.54 °C), were determined. There was a brain cooling effect during in vivo MRSI of 0.10 °C [95% confidence interval (CI): -0.110, -0.094 °C; p < 0.001] and 0.051 °C (95% CI: -0.054, -0.048 °C; p < 0.001) per scan at 1.5 T and 3 T, respectively, whereas phantom measurements revealed minimal drift in apparent MRSI temperature relative to fibre-optic temperature measurements. The mean brain temperature at 3 T was weakly associated with aural (R = 0.55, p = 0.002) and oral (R = 0.62, p < 0.001) measurements of head temperature. In conclusion, the variability associated with MRSI brain temperature mapping was

  18. Reliability of MRSI brain temperature mapping at 1.5 and 3 T

    PubMed Central

    Thrippleton, Michael J; Parikh, Jehill; Harris, Bridget A; Hammer, Steven J; Semple, Scott I K; Andrews, Peter J D; Wardlaw, Joanna M; Marshall, Ian

    2014-01-01

    MRSI permits the non-invasive mapping of brain temperature in vivo, but information regarding its reliability is lacking. We obtained MRSI data from 31 healthy male volunteers [age range, 22–40 years; mean ± standard deviation (SD), 30.5 ± 5.0 years]. Eleven subjects (age range, 23–40 years; mean ± SD, 30.5 ± 5.2 years) were invited to receive four point-resolved spectroscopy MRSI scans on each of 3 days in both 1.5-T (TR/TE = 1000/144 ms) and 3-T (TR/TE = 1700/144 ms) clinical scanners; a further 20 subjects (age range, 22–40 years; mean ± SD, 30.5 ± 4.9 years) were scanned on a single occasion at 3 T. Data were fitted in the time domain to determine the water–N-acetylaspartate chemical shift difference, from which the temperature was estimated. Temperature data were analysed using a linear mixed effects model to determine variance components and systematic temperature changes during the scanning sessions. To characterise the effects of instrumental drift on apparent MRSI brain temperature, a temperature-controlled phantom was constructed and scanned on multiple occasions. Components of apparent in vivo temperature variability at 1.5 T/3 T caused by inter-subject (0.18/0.17 °C), inter-session (0.18/0.15 °C) and within-session (0.36/0.14 °C) effects, as well as voxel-to-voxel variation (0.59/0.54 °C), were determined. There was a brain cooling effect during in vivo MRSI of 0.10 °C [95% confidence interval (CI): –0.110, –0.094 °C; p < 0.001] and 0.051 °C (95% CI: –0.054, –0.048 °C; p < 0.001) per scan at 1.5 T and 3 T, respectively, whereas phantom measurements revealed minimal drift in apparent MRSI temperature relative to fibre-optic temperature measurements. The mean brain temperature at 3 T was weakly associated with aural (R = 0.55, p = 0.002) and oral (R = 0.62, p < 0.001) measurements of head temperature. In conclusion, the variability associated with MRSI brain temperature

  19. Identification of a 3rd Na+ Binding Site of the Glycine Transporter, GlyT2

    PubMed Central

    Subramanian, Nandhitha; Scopelitti, Amanda J.; Carland, Jane E.; Ryan, Renae M.; O’Mara, Megan L.; Vandenberg, Robert J.

    2016-01-01

    The Na+/Cl- dependent glycine transporters GlyT1 and GlyT2 regulate synaptic glycine concentrations. Glycine transport by GlyT2 is coupled to the co-transport of three Na+ ions, whereas transport by GlyT1 is coupled to the co-transport of only two Na+ ions. These differences in ion-flux coupling determine their respective concentrating capacities and have a direct bearing on their functional roles in synaptic transmission. The crystal structures of the closely related bacterial Na+-dependent leucine transporter, LeuTAa, and the Drosophila dopamine transporter, dDAT, have allowed prediction of two Na+ binding sites in GlyT2, but the physical location of the third Na+ site in GlyT2 is unknown. A bacterial betaine transporter, BetP, has also been crystallized and shows structural similarity to LeuTAa. Although betaine transport by BetP is coupled to the co-transport of two Na+ ions, the first Na+ site is not conserved between BetP and LeuTAa, the so called Na1' site. We hypothesized that the third Na+ binding site (Na3 site) of GlyT2 corresponds to the BetP Na1' binding site. To identify the Na3 binding site of GlyT2, we performed molecular dynamics (MD) simulations. Surprisingly, a Na+ placed at the location consistent with the Na1' site of BetP spontaneously dissociated from its initial location and bound instead to a novel Na3 site. Using a combination of MD simulations of a comparative model of GlyT2 together with an analysis of the functional properties of wild type and mutant GlyTs we have identified an electrostatically favorable novel third Na+ binding site in GlyT2 formed by Trp263 and Met276 in TM3, Ala481 in TM6 and Glu648 in TM10. PMID:27337045

  20. Test – Retest Reliability and Concurrent Validity of in vivo Myelin Content Indices: Myelin Water Fraction and Calibrated T1w/T2w Image Ratio

    PubMed Central

    Arshad, Muzamil; Stanley, Jeffrey A.; Raz, Naftali

    2016-01-01

    In an age-heterogeneous sample of healthy adults, we examined test-retest reliability (with and without participant re-positioning) of two popular MRI methods of estimating myelin content: modeling the short spin-spin (T2) relaxation component of multi-echo imaging data and computing the ratio of T1-weighted and T2-weighted images (T1w/T2w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi-component T2 relaxation data as a standard, we evaluate the concurrent and differential validity of T1w/T2w ratio images. The results revealed high reliability of MWF and T1w/T2w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T1w/T2w ratio in only two of six examined regions of the cerebral white matter. Notably, significant correlations of the same or greater magnitude were observed for T1w/T2w ratio and the intermediate T2 relaxation time constant, which is believed to reflect differences in the mobility of water between the intracellular and extracellular compartments. We conclude that although both methods are highly reliable and thus well-suited for longitudinal studies, T1w/T2w ratio has low criterion validity and may be not an optimal index of subcortical myelin content. PMID:28009069

  1. Heavy neutrino mixing in the T2HK, the T2HKK and an extension of the T2HK with a detector at Oki Islands

    NASA Astrophysics Data System (ADS)

    Abe, Yugo; Asano, Yusuke; Haba, Naoyuki; Yamada, Toshifumi

    2017-12-01

    We study the discovery potential for the mixing of heavy isospin-singlet neutrinos in extensions of the Tokai-to-Kamioka (T2K) experiment, the Tokai-to-Hyper-Kamiokande (T2HK), the Tokai-to-Hyper-Kamiokande-to-Korea (T2HKK) with a Korea detector with ˜eq 1000 km baseline length and 1° off-axis angle, and a plan of adding a small detector at Oki Islands to the T2HK. We further pursue the possibility of measuring the neutrino mass hierarchy and the standard CP-violating phase δ _{CP} in the presence of heavy neutrino mixing by fitting data with the standard oscillation parameters only. We show that the sensitivity to heavy neutrino mixing is highly dependent on δ _{CP} and new CP-violating phases in the heavy neutrino mixing matrix, and deteriorates considerably when these phases conspire to suppress interference between the standard oscillation amplitude and an amplitude arising from heavy neutrino mixing, at the first oscillation peak. Although this suppression is avoided by the use of a beam with smaller off-axis angle, the T2HKK and the T2HK+small Oki detector do not show improvement over the T2HK. As for the mass hierarchy measurement, the wrong mass hierarchy is possibly favored in the T2HK because heavy neutrino mixing can mimic matter effects. In contrast, the T2HKK and the T2HK+small Oki detector are capable of correctly measuring the mass hierarchy despite heavy neutrino mixing, as measurements with different baselines resolve degeneracy between heavy neutrino mixing and matter effects. Notably, adding a small detector at Oki to the T2HK drastically ameliorates the sensitivity, which is the central appeal of this paper. As for the δ _{CP} measurement, there can be a sizable discrepancy between the true δ _{CP} and the value obtained by fitting data with the standard oscillation parameters only, which can be comparable to 1σ resolution of the δ _{CP} measurement. Hence, if a hint of heavy neutrino mixing is discovered, it is necessary to incorporate

  2. A Novel Regulatory Function of Sweet Taste-Sensing Receptor in Adipogenic Differentiation of 3T3-L1 Cells

    PubMed Central

    Masubuchi, Yosuke; Nakagawa, Yuko; Ma, Jinhui; Sasaki, Tsutomu; Kitamura, Tadahiro; Yamamoto, Yoritsuna; Kurose, Hitoshi; Kojima, Itaru; Shibata, Hiroshi

    2013-01-01

    Background Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells. Methodology/Principal Findings In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6). The α subunits of Gs (Gαs) and G14 (Gα14) but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects. Conclusions 3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism. PMID:23336004

  3. 26 CFR 1.410(a)-3T - Minimum age and service conditions (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Minimum age and service conditions (temporary). 1.410(a)-3T Section 1.410(a)-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.410(a)-3T Minimum age and service conditions (temporary). (a) [Reserved] (b) Special...

  4. 26 CFR 1.410(a)-3T - Minimum age and service conditions (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Minimum age and service conditions (temporary). 1.410(a)-3T Section 1.410(a)-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE.... § 1.410(a)-3T Minimum age and service conditions (temporary). (a) [Reserved] (b) Special rule for plan...

  5. Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion.

    PubMed

    Utz, U; Banks, D; Jacobson, S; Biddison, W E

    1996-02-01

    Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers, show very high precursor frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific T cells were demonstrated to be directed predominantly against one HTLV-1 epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An analysis of the T-cell receptor (TCR) repertoire of these cells revealed an absence of restricted variable (V) region usage. Different combinations of TCR V alpha and V beta genes were utilized between, but also within, the individual patients for the recognition of Tax11-19. Sequence analysis of the TCR showed evidence for an oligoclonal expansion of few founder T cells in each patient. Apparent structural motifs were identified for the CDR3 regions of the TCR beta chains. One T-cell clone could be detected within the same patient over a period of 3 years. We suggest that these in vivo clonally expanded T cells might play a role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific TCR which may elucidate the nature of the T cells that infiltrate the central nervous system in HAM/TSP patients.

  6. Infiltration of γ⁢δ T cells, IL-17+ T cells and FoxP3+ T cells in human breast cancer

    PubMed Central

    Allaoui, Roni; Hagerling, Catharina; Desmond, Eva; Warfvinge, Carl-Fredrik; Jirström, Karin; Leandersson, Karin

    2017-01-01

    BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have a strong prognostic value in various forms of cancers. These data often refer to use of the pan-T cell marker CD3, or the cytotoxic T lymphocyte marker CD8α. However, T cells are a heterogeneous group of cells with a wide array of effector mechanisms ranging from immunosuppression to cytotoxicity. OBJECTIVE: In this study we have investigated the prognostic effects of some unconventional T cell subtypes in breast cancer; γ⁢δ T cells, IL-17+ T cells and FoxP3+ T cells (Tregs) in relation to the conventional CD3 and CD8α T cell markers. METHODS: This was done using immunohistochemistry on a human breast cancer tissue microarray consisting of 498 consecutive cases of primary breast cancer. RESULTS: Infiltration of γ⁢δ T cells and T cell infiltration in general (CD3), correlated with a good prognosis, while Treg infiltration with a worse. Infiltration of γ⁢δ T cells was associated with a significantly improved clinical outcome in all breast cancer subtypes except triple negative tumors. Only infiltration of either CD3+ or CD8α+ cells was independently associated with better prognosis for all breast cancer patients. CONCLUSIONS: This study sheds further light on the prognostic impact of various T cell subtypes in breast cancer. PMID:29060923

  7. Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma.

    PubMed

    Persky, Michael J; Albergotti, William G; Rath, Tanya J; Kubik, Mark W; Abberbock, Shira; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L

    2018-04-01

    Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

  8. [Liver and heart T2* measurement in secondary haemochromatosis].

    PubMed

    Barrera Portillo, M C; Uranga Uranga, M; Sánchez González, J; Alústiza Echeverría, J M; Gervás Wells, C; Guisasola Íñiguez, A

    2013-01-01

    To determine whether there is iron overload by calculating the T2* value in the liver and myocardium in patients with secondary haemochromatosis. To analyse the correlation of the values obtained with the iron levels in blood, with the liver iron concentration (LIC) calculated using magnetic resonance (MR) imaging, and the correlation between them. A total of 16 patients (13 males, 3 females), with a mean age of 61 years, were included and evaluated in the years 2008 and 2009. Fifteen of them had received multiple transfusions, and one was diagnosed with hereditary sideroblastic anaemia. The measurements included, blood ferritin, LIC by MRI, cardiac function using MRI and the T2* value by means of multi-echo sequences in the liver (TR/TE1/ΔTE/No of echos/α: 21/1,18/1.0/20/35°) and myocardium (26/1.04/0.8/30/60°). A correlation-regression analysis was performed by comparing the cardiac and liver T2* values with the ferritin, LIC and between each of them. A total of 13 patients had ferritin values greater than 1000ng/ml (median/minimum/maximum: 1762/294/3785ng/ml). An increased LIC greater than 80μmol/g (median/minimum/maximum: 125.4/41.2/241.5μmol/g) was observed in 13 patients. In all cases cardiac function was conserved, and in 15 cases the liver T2* value was less than 6.3ms. The myocardium T2* value was less than 20ms. in only one case. A high correlation was observed between the liver T2* values and the LIC (r:-0.912). The correlation was statistically significant between the liver T2* value and ferritin (r:-0.541). The correlations between myocardium T2* and ferritin, myocardium T2* and LIC, and myocardium T2* and liver T2* were not statistically significant. The liver T2* showed a high correlation with LIC and a statistically significant correlation with ferritin. No association was observed between the myocardium T2* values and ferritin in blood, the LIC or the liver T2* value. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  9. 26 CFR 1.904(g)-2T - Recapture of overall domestic losses (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...). 1.904(g)-2T Section 1.904(g)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... States § 1.904(g)-2T Recapture of overall domestic losses (temporary). (a) In general. A taxpayer shall... increased. As provided in § 1.904(g)-1T(f)(2), the balance in a taxpayer's overall domestic loss account...

  10. 26 CFR 1.904(g)-2T - Recapture of overall domestic losses (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...). 1.904(g)-2T Section 1.904(g)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... States § 1.904(g)-2T Recapture of overall domestic losses (temporary). (a) In general. A taxpayer shall... increased. As provided in § 1.904(g)-1T(f)(2), the balance in a taxpayer's overall domestic loss account...

  11. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis.

    PubMed

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2017-05-01

    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  12. 26 CFR 1.410(a)-3T - Minimum age and service conditions (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Minimum age and service conditions (temporary). 1.410(a)-3T Section 1.410(a)-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY.... § 1.410(a)-3T Minimum age and service conditions (temporary). (a) [Reserved] (b) Special rule for plan...

  13. Measurement of the mass difference between t and t quarks.

    PubMed

    Aaltonen, T; Álvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Apresyan, A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bauer, G; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Brisuda, A; Bromberg, C; Brucken, E; Bucciantonio, M; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Dagenhart, D; d'Ascenzo, N; Datta, M; de Barbaro, P; De Cecco, S; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Devoto, F; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, M; Dorigo, T; Ebina, K; Elagin, A; Eppig, A; Erbacher, R; Errede, D; Errede, S; Ershaidat, N; Eusebi, R; Fang, H C; Farrington, S; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Funakoshi, Y; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, S R; Halkiadakis, E; Hamaguchi, A; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Hewamanage, S; Hidas, D; Hocker, A; Hopkins, W; Horn, D; Hou, S; Hughes, R E; Hurwitz, M; Husemann, U; Hussain, N; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirby, M; Klimenko, S; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kuhr, T; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leo, S; Leone, S; Lewis, J D; Lin, C-J; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, Q; Liu, T; Lockwitz, S; Lockyer, N S; Loginov, A; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maeshima, K; Makhoul, K; Maksimovic, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Martínez, M; Martínez-Ballarín, R; Mastrandrea, P; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Potamianos, K; Poukhov, O; Prokoshin, F; Pronko, A; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Rescigno, M; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rubbo, F; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Sakurai, Y; Santi, L; Sartori, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shreyber, I; Simonenko, A; Sinervo, P; Sissakian, A; Sliwa, K; Smith, J R; Snider, F D; Soha, A; Somalwar, S; Sorin, V; Squillacioti, P; Stancari, M; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Tu, Y; Ukegawa, F; Uozumi, S; Varganov, A; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wagner, R L; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Wick, F; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamaoka, J; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zucchelli, S

    2011-04-15

    We present a direct measurement of the mass difference between t and t quarks using tt candidate events in the lepton+jets channel, collected with the CDF II detector at Fermilab's 1.96 TeV Tevatron pp Collider. We make an event by event estimate of the mass difference to construct templates for top quark pair signal events and background events. The resulting mass difference distribution of data is compared to templates of signals and background using a maximum likelihood fit. From a sample corresponding to an integrated luminosity of 5.6  fb(-1), we measure a mass difference, ΔM(top) = M(t) - M(t) = -3.3 ± 1.4(stat) ± 1.0(syst)  GeV/c2, approximately 2 standard deviations away from the CPT hypothesis of zero mass difference.

  14. Prostate Postbrachytherapy Seed Distribution: Comparison of High-Resolution, Contrast-Enhanced, T1- and T2-Weighted Endorectal Magnetic Resonance Imaging Versus Computed Tomography: Initial Experience

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bloch, B. Nicolas; Department of Radiology, General Hospital Vienna, Medical University Vienna, Vienna; Lenkinski, Robert E.

    2007-09-01

    Purpose: To compare contrast-enhanced, T1-weighted, three-dimensional magnetic resonance imaging (CEMR) and T2-weighted magnetic resonance imaging (T2MR) with computed tomography (CT) for prostate brachytherapy seed location for dosimetric calculations. Methods and Materials: Postbrachytherapy prostate MRI was performed on a 1.5 Tesla unit with combined surface and endorectal coils in 13 patients. Both CEMR and T2MR used a section thickness of 3 mm. Spiral CT used a section thickness of 5 mm with a pitch factor of 1.5. All images were obtained in the transverse plane. Two readers using CT and MR imaging assessed brachytherapy seed distribution independently. The dependency of datamore » read by both readers for a specific subject was assessed with a linear mixed effects model. Results: The mean percentage ({+-} standard deviation) values of the readers for seed detection and location are presented. Of 1205 implanted seeds, CEMR, T2MR, and CT detected 91.5% {+-} 4.8%, 78.5% {+-} 8.5%, and 96.1% {+-} 2.3%, respectively, with 11.8% {+-} 4.5%, 8.5% {+-} 3.5%, 1.9% {+-} 1.0% extracapsular, respectively. Assignment to periprostatic structures was not possible with CT. Periprostatic seed assignments for CEMR and T2MR, respectively, were as follows: neurovascular bundle, 3.5% {+-} 1.6% and 2.1% {+-} 0.9%; seminal vesicles, 0.9% {+-} 1.8% and 0.3% {+-} 0.7%; periurethral, 7.1% {+-} 3.3% and 5.8% {+-} 2.9%; penile bulb, 0.6% {+-} 0.8% and 0.3% {+-} 0.6%; Denonvillier's Fascia/rectal wall, 0.5% {+-} 0.6% and 0%; and urinary bladder, 0.1% {+-} 0.3% and 0%. Data dependency analysis showed statistical significance for the type of imaging but not for reader identification. Conclusion: Both enumeration and localization of implanted seeds are readily accomplished with CEMR. Calculations with MRI dosimetry do not require CT data. Dose determinations to specific extracapsular sites can be obtained with MRI but not with CT.« less

  15. Changes in the T2 value of cartilage after meniscus transplantation over 1 year.

    PubMed

    Park, Sun-Young; Lee, Sang Hoon; Lee, Min Hee; Chung, Hye Won; Shin, Myung Jin

    2017-04-01

    To evaluate the changes in the mean T2 values of articular cartilage on serial follow-up images up to 1 year in patients who underwent lateral meniscus allograft transplantation (MAT). Fifty-two patients who underwent lateral MAT surgery at our hospital were evaluated preoperatively and at 2 days, 6 weeks, 3 months, 6 months, and 1 year after MAT using 3.0-T magnetic resonance imaging (MRI) that included T2 mapping. T2 value changes according to the arthroscopic grading of chondromalacia were evaluated in the lateral and medial compartment. Lysholm scores were obtained pre- and postoperatively. The T2 values of cartilage were significantly increased 2 days after operation, and then gradually reduced to the baseline level after 1 year in both compartments. In morphologic assessment performed after 1 year, most areas (92.9 %) showed no interval change of chondromalacia grade. Lyshom knee scores increased significantly from the mean preoperative value of 62.5 (range, 23-95) to 89.7 (range, 64-100) at 1 year (p < 0.001). Mean T2 values of cartilage following MAT exhibited a return to baseline level after 1 year. T2 measurement can be a useful tool for quantitative evaluation of postoperative cartilage changes compared to conventional MRI. • T2 mapping provides objective data for longitudinal monitoring following surgery. • Increased cartilage T2 values post-MAT returned to baseline in one year. • Further studies are required to predict the chondroprotective effect of MAT.

  16. miR-29a-3p/T-bet Regulatory Circuit Is Altered in T Cells of Patients With Hashimoto's Thyroiditis.

    PubMed

    Tokić, Stana; Štefanić, Mario; Glavaš-Obrovac, Ljubica; Kishore, Amit; Navratilova, Zdenka; Petrek, Martin

    2018-01-01

    Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder that frequently evolves from asymptomatic, T-cell mediated chronic inflammation toward overt hypothyroidism. Previously, we have demonstrated a role for T-bet, a T helper 1/CD8 + T cell transcription factor (TF), and FoxP3, a regulatory T cell TF, in disease progression and severity, but the basis behind their altered mRNA expression remains unknown. In this study, we aimed to leverage the role for microRNAs, representing negative transcriptional regulators, across the spectrum of HT clinical presentations using the same, well-characterized RNA sample cohort. Ten hypothyroid, untreated patients (hypoHT), 10 hypothyroid cases rendered euthyroid by l-thyroxine therapy (substHT), 11 spontaneously euthyroid HT subjects (euHT), and 10 healthy controls (ctrl) were probed for three candidate immunoregulatory miRNA (miR-9-5p, miR-29a-3p, and miR-210-3p) using quantitative real-time PCR measurements. Data were normalized to U6snRNA and fold difference in expression calculated by the efficiency corrected 2 -ΔΔCt model. Compared to healthy controls, peripheral blood (PB) T cells of HT patients exhibited significantly diminished miR-29a-3p expression levels [median expression levels (IQR), HT vs CTRL, 0.62 (0.44-1.01) vs 1.373 (0.63-2.7), P  = 0.046], and a similar, but not significant decline in miR-210-3p abundance [HT vs CTRL, 0.64 (0.39-1.31) vs 1.2 (0.5-2.56), P  = 0.24, Wilcoxon test]. A significant inverse correlation was observed between the two differentially expressed transcripts, T-bet mRNA and miR-29a-3p. Moreover, altered miR-29a-3p/T-bet expression in T cells of untreated HT patients was related to low serum FT4, high serum thyrotropin, and decreased thyroid volumes. Of note, miR-210-3p expression was positively correlated to HIF1α, and inversely to FoxP3 mRNA levels, but no evidence of differential expression for any of these miRNA-mRNA pairs was observed. Finally, miR-9-5p

  17. Cannabidiol promotes browning in 3T3-L1 adipocytes.

    PubMed

    Parray, Hilal Ahmad; Yun, Jong Won

    2016-05-01

    Recruitment of the brown-like phenotype in white adipocytes (browning) and activation of existing brown adipocytes are currently being investigated as a means to combat obesity. Thus, a wide variety of dietary agents that contribute to browning of white adipocytes have been identified. The present study was designed to investigate the effects of cannabidiol (CBD), a major nonpsychotropic phytocannabinoid of Cannabis sativa, on induction of browning in 3T3-L1 adipocytes. CBD enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cited1, Tmem26, Prdm16, Cidea, Tbx1, Fgf21, and Pgc-1α) and proteins (UCP1, PRDM16, and PGC-1α). Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly via activation of PPARγ and PI3K. In addition, CBD increased protein expression levels of CPT1, ACSL, SIRT1, and PLIN while down-regulating JNK2, SREBP1, and LPL. These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. In conclusion, the current data suggest that CBD plays dual modulatory roles in the form of inducing the brown-like phenotype as well as promoting lipid metabolism. Thus, CBD may be explored as a potentially promising therapeutic agent for the prevention of obesity.

  18. 26 CFR 1.904(g)-2T - Recapture of overall domestic losses (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...). 1.904(g)-2T Section 1.904(g)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE....904(g)-2T Recapture of overall domestic losses (temporary). (a) In general. A taxpayer shall recapture... provided in § 1.904(g)-1T(f)(2), the balance in a taxpayer's overall domestic loss account with respect to...

  19. Lingering fat signals with CHESS in simultaneous imaging of both hands can be improved with rice pads in both 1.5T and 3.0T.

    PubMed

    Moriya, Susumu; Miki, Yukio; Kamishima, Tamotsu; Miyati, Tosiaki; Kanagaki, Mitsunori; Matsuno, Yukako; Yokobayashi, Tsuneo

    2013-09-01

    To investigate whether rice pads can eliminate lingering fat signals of the complex surface shape of both hands that occur with chemical shift selective (CHESS) at 1.5T and 3.0T. T1-weighted images were obtained with CHESS using 1.5T and 3.0T systems. The same imaging parameters were used with and without rice pads on the coronal plane of both hands in 10 healthy volunteers. The fat-suppression effects were classified into four categories and scored for images, and visual evaluations were performed by one radiologist and one radiologic technologist. At 1.5T, the mean evaluation score was 1.55 for images obtained without rice pads and 3.50 for images obtained with rice pads. At 3.0T, the mean evaluation score was 1.10 for images obtained without rice pads and 3.20 for images obtained with rice pads. With both systems, images obtained with the rice pads showed significantly better fat suppression effects than images obtained without rice pads (P<0.0001, P<0.0001). It was confirmed that lingering fat signals are eliminated and good fat-suppressed images are obtained with the use of rice pads at 1.5T and 3.0T. Rice pads are therefore useful with at 1.5T and 3.0T, which are currently becoming more widely used. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Transanal Endoscopic Microsurgery with or without Completion Total Mesorectal Excision for T2 and T3 Rectal Carcinoma.

    PubMed

    Leijtens, Jeroen W A; Koedam, Thomas W A; Borstlap, Wernard A A; Maas, Monique; Doornebosch, Pascal G; Karsten, Tom M; Derksen, Eric J; Stassen, Laurents P S; Rosman, Camiel; de Graaf, Eelco J R; Bremers, André J A; Heemskerk, Jeroen; Beets, Geerard L; Tuynman, Jurriaan B; Rademakers, Kevin L J

    2018-05-23

    Transanal endoscopic microsurgery (TEM) is used for the resection of large rectal adenomas and well or moderately differentiated T1 carcinomas. Due to difficulty in preoperative staging, final pathology may reveal a carcinoma not suitable for TEM. Although completion total mesorectal excision is considered standard of care in T2 or more invasive carcinomas, this completion surgery is not always performed. The purpose of this article is to evaluate the outcome of patients after TEM-only, when completion surgery would be indicated. In this retrospective multicenter, observational cohort study, outcome after TEM-only (n = 41) and completion surgery (n = 40) following TEM for a pT2-3 rectal adenocarcinoma was compared. Median follow-up was 29 months for the TEM-only group and 31 months for the completion surgery group. Local recurrence rate was 35 and 11% for the TEM-only and completion surgery groups respectively. Distant metastasis occurred in 16% of the patients in both groups. The 3-year overall survival was 63% in the TEM-only group and 91% in the completion surgery group respectively. Three-year disease-specific survival was 91 versus 93% respectively. Although local recurrence after TEM-only for pT2-3 rectal cancer is worse compared to the recurrence that occurs after completion surgery, disease-specific survival is comparable between both groups. The lower unadjusted overall survival in the TEM-only group indicates that TEM-only may be a valid alternative in older and frail patients, especially when high morbidity of completion surgery is taken into consideration. Nevertheless, completion surgery should always be advised when curation is intended. © 2018 The Author(s) Published by S. Karger AG, Basel.

  1. Space shuttle: Aerodynamic characteristics of various MDAC space shuttle ascent configurations with parallel burn pressure-fed and SRM boosters. Volume 1: Tanks T1 and T2 ascent configurations

    NASA Technical Reports Server (NTRS)

    Jarrett, T. W.

    1972-01-01

    Various space shuttle ascent configurations were tested in a trisonic wind tunnel to determine the aerodynamic characteristics. The ascent configuration consisted of a NASA/MSC 040 orbiter in combination with various HO centerline tank and booster geometries. The aerodynamic interference between components of the space shuttle and the effect on the orbiter aerodynamics was determined. The various aerodynamic configurations tested were: (1) centerline HO tanks T1 and T2, (2) centerline HO tank T3, and (3) centerline HO tank H4.

  2. T3 supplementation affects ventilatory timing & glucose levels in type 2 diabetes mellitus model.

    PubMed

    Bollinger, Stephen S; Weltman, Nathen Y; Gerdes, A Martin; Schlenker, Evelyn H

    2015-01-01

    Type II diabetes mellitus (T2DM) can affect ventilation, metabolism, and fasting blood glucose levels. Hypothyroidism may be a comorbidity of T2DM. In this study T2DM was induced in 20 female Sprague Dawley rats using Streptozotocin (STZ) and Nicotinamide (N). One of experimental STZ/N groups (N=10 per group) was treated with a low dose of triiodothyronine (T3). Blood glucose levels, metabolism and ventilation (in air and in response to hypoxia) were measured in the 3 groups. STZ/N-treated rats increased fasting blood glucose compared to control rats eight days and 2 months post-STZ/N injections indicating stable induction of T2DM state. Treatments had no effects on ventilation, metabolism or body weight. After one month of T3 supplementation, there were no physiological indications of hyperthyroidism, but T3 supplementation altered ventilatory timing and decreased blood glucose levels compared to STZ/N rats. These results suggest that low levels of T3 supplementation could offer modest effects on blood glucose and ventilatory timing in this T2M model. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Nonstandard neutrino interactions at DUNE, T2HK and T2HKK

    DOE PAGES

    Liao, Jiajun; Marfatia, Danny; Whisnant, Kerry

    2017-01-17

    Here, we study the matter effect caused by nonstandard neutrino interactions (NSI) in the next generation long-baseline neutrino experiments, DUNE, T2HK and T2HKK. If multiple NSI parameters are nonzero, the potential of these experiments to detect CP violation, determine the mass hierarchy and constrain NSI is severely impaired by degeneracies between the NSI parameters and by the generalized mass hierarchy degeneracy. In particular, a cancellation between leading order terms in the appearance channels when ϵ eτ= cot θ 23ϵ eμ, strongly affects the sensitivities to these two NSI parameters at T2HK and T2HKK. We also study the dependence of themore » sensitivities on the true CP phase and the true mass hierarchy, and find that overall DUNE has the best sensitivity to the magnitude of the NSI parameters, while T2HKK has the best sensitivity to CP violation whether or not there are NSI. Furthermore, for T2HKK a smaller off-axis angle for the Korean detector is better overall. We find that due to the structure of the leading order terms in the appearance channel probabilities, the NSI sensitivities in a given experiment are similar for both mass hierarchies, modulo the phase change δ→δ + 180°.« less

  4. Nonstandard neutrino interactions at DUNE, T2HK and T2HKK

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liao, Jiajun; Marfatia, Danny; Whisnant, Kerry

    Here, we study the matter effect caused by nonstandard neutrino interactions (NSI) in the next generation long-baseline neutrino experiments, DUNE, T2HK and T2HKK. If multiple NSI parameters are nonzero, the potential of these experiments to detect CP violation, determine the mass hierarchy and constrain NSI is severely impaired by degeneracies between the NSI parameters and by the generalized mass hierarchy degeneracy. In particular, a cancellation between leading order terms in the appearance channels when ϵ eτ= cot θ 23ϵ eμ, strongly affects the sensitivities to these two NSI parameters at T2HK and T2HKK. We also study the dependence of themore » sensitivities on the true CP phase and the true mass hierarchy, and find that overall DUNE has the best sensitivity to the magnitude of the NSI parameters, while T2HKK has the best sensitivity to CP violation whether or not there are NSI. Furthermore, for T2HKK a smaller off-axis angle for the Korean detector is better overall. We find that due to the structure of the leading order terms in the appearance channel probabilities, the NSI sensitivities in a given experiment are similar for both mass hierarchies, modulo the phase change δ→δ + 180°.« less

  5. Observation of exchange of micropore water in cement pastes by two-dimensional T(2)-T(2) nuclear magnetic resonance relaxometry.

    PubMed

    Monteilhet, L; Korb, J-P; Mitchell, J; McDonald, P J

    2006-12-01

    The first detailed analysis of the two-dimensional (2D) NMR T(2)-T(2) exchange experiment with a period of magnetization storage between the two T(2) relaxation encoding periods (T(2)-store-T(2)) is presented. It is shown that this experiment has certain advantages over the T(1)-T(2) variant for the quantization of chemical exchange. New T(2)-store-T(2) 2D 1H NMR spectra of the pore water within white cement paste are presented. Based on these spectra, the exchange rate of water between the two smallest porosity reservoirs is estimated for the first time. It is found to be of the order of 5 ms{-1}. Further, a careful estimate of the pore sizes of these reservoirs is made. They are found to be of the order of 1.4 nm and 10-30 nm , respectively. A discussion of the results is developed in terms of possible calcium silicate hydrate products. A water diffusion coefficient inferred from the exchange rate and the cement particle size is found to compare favorably with the results of molecular-dynamics simulations to be found in the literature.

  6. Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells.

    PubMed

    Ding, Ling-Zhi; Teng, Xiao; Zhang, Zhao-Bo; Zheng, Chang-Jun; Chen, Shi-Hong

    2018-05-01

    Mangiferin is a xanthone glucoside, which possesses antioxidant, antiviral, antitumor and anti-inflammatory functions, and is associated with gene regulation. However, it remains unknown whether mangiferin protects osteoblasts, such as the MC3T3-E1 cell line, against glucocorticoid-induced damage. In the present study, MC3T3-E1 cells were treated with dexamethasone (Dex), which is a well-known synthetic glucocorticoid, in order to establish a glucocorticoid-induced cell injury model. After Dex and/or mangiferin treatment, cell viability, apoptosis and reactive oxygen species (ROS) production was measured by Cell Counting kit-8 (CCK-8) and flow cytometry, respectively, and the concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and macrophage colony-stimulating factor (M-CSF) was measured by ELISA. The expression of bone morphogenetic protein 2 (BMP2), phosphorylated‑SMAD family member 1 (p-Smad-1), t-Smad-1, osterix (OSX), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), B‑cell lymphoma 2 (Bcl-2) and Bcl‑2‑associated X protein (Bax) was measured by real-time PCR and/or western blot analysis. The results indicated that pretreatment of MC3T3-E1 cells with mangiferin for 3 h prior to exposure to Dex for 48 h significantly attenuated Dex-induced injury and inflammation, as demonstrated by increased cell viability, and decreases in apoptosis, ROS generation, and the secretion of TNF-α, IL-6 and M-CSF. In addition, pretreatment with mangiferin markedly reduced Dex-induced BMP2 and p‑Smad-1 downregulation, and corrected the expression of differentiation‑ and apoptosis‑associated markers, including alkaline phosphatase, OSX, OCN, OPG, RANK, RANKL, Bcl-2 and Bax, which were altered by Dex treatment. Similar to the protective effects of mangiferin, overexpression of BMP2 suppressed not only Dex-induced cytotoxicity, but also ROS generation, and the secretion of TNF

  7. miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1 cells via targeting RAF-1.

    PubMed

    Chao, Chen; Li, Feng; Tan, Zhiping; Zhang, Weizhi; Yang, Yifeng; Luo, Cheng

    2018-01-15

    Recent reports have demonstrated that RAF-1 L613V (a mutant of RAF-1) mutant mice show bone deformities similar to Noonan syndrome. It has been suggested that RAF-1 L613V might abnormally activate osteoblast differentiation of MC3T3-E1 cells. To demonstrate that RAF-1 is associated with bone deformity and that RAF-1 L613V dependent bone deformity could be inhibited by microRNA-195 (miR-195), we first investigated the amplifying influence of wild-type RAF-1 (WT) or RAF-1 L613V (L613V) on the viability and differentiation of MC3T3-E1 cells induced by bone morphogenetic protein-2 (BMP-2) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Subsequently, we investigated the blocking effect and its mechanism of miR-195 for abnormal activation of osteoblast differentiation of MC3T3-E1 cells via targeting RAF-1. RAF-1, especially RAF-1 L613V , abnormally activates osteoblast differentiation of MC3T3-E1 cells induced by BMP-2. Meanwhile, miR-195 could inhibit the cell viability and differentiation of MC3T3-E1 cells. Transfection of miR-195 largely suppressed the L613V-induced viability and osteoblast differentiation of MC3T3-E1 cells and attenuated the accelerative effect of L613V on runt-related transcription factor-2 (Runx2), Osterix (OSX), alkaline phosphatase (ALP), osteocalcin (OCN), and distal-less homeobox 5 (DLX5) osteogenic gene expressions. In addition, miR-195 decreased the expression of RAF-1 mRNA and protein by directly targeting the 3'-untranslated regions (3'-UTR) of RAF-1 mRNA in MC3T3-E1 cells. Our findings indicated that miR-195 inhibited WT and L613V RAF-1 induced hyperactive osteoblast differentiation in MC3T3-E1 cells by targeting RAF-1. miR-195 might be a novel therapeutic agent for the treatment of L613V-induced bone deformity in Noonan syndrome. Copyright © 2017. Published by

  8. Taste information derived from T1R-expressing taste cells in mice.

    PubMed

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-03-01

    The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination. © 2016 Authors; published by Portland Press Limited.

  9. Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

    PubMed

    Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

    2015-03-01

    Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

  10. Co-Introduced Functional CCR2 Potentiates In Vivo Anti-Lung Cancer Functionality Mediated by T Cells Double Gene-Modified to Express WT1-Specific T-Cell Receptor

    PubMed Central

    Asai, Hiroaki; Fujiwara, Hiroshi; An, Jun; Ochi, Toshiki; Miyazaki, Yukihiro; Nagai, Kozo; Okamoto, Sachiko; Mineno, Junichi; Kuzushima, Kiyotaka; Shiku, Hiroshi; Inoue, Hirofumi; Yasukawa, Masaki

    2013-01-01

    Background and Purpose Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR) or chimeric antigen receptor (CAR) has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor. Methodology/Principal Findings Human lung cancer cells variously express a tumor antigen, Wilms' Tumor gene product 1 (WT1), and an inflammatory chemokine, CCL2. However, CCR2, the relevant receptor for CCL2, is rarely expressed on activated T-lymphocytes. A HLA-A2402+ human lung cancer cell line, LK79, which expresses high amounts of both CCL2 and WT1 mRNA, was employed as a target. Normal CD8+ T cells were retrovirally gene-modified to express both CCR2 and HLA-A*2402-restricted and WT1235–243 nonapeptide-specific TCR as an effector. Anti-tumor functionality mediated by these effector cells against LK79 cells was assessed both in vitro and in vivo. Finally the impact of CCL2 on WT1 epitope-responsive TCR signaling mediated by the effector cells was studied. Introduced CCR2 was functionally validated using gene-modified Jurkat cells and human CD3+ T cells both in vitro and in vivo. Double gene-modified CD3+ T cells successfully demonstrated both CCL2-tropic tumor trafficking and cytocidal reactivity against LK79 cells in vitro and in vivo. CCL2 augmented the WT1 epitope-responsive TCR signaling shown by relevant luciferase production in double gene-modified Jurkat/MA cells to express luciferase and WT1-specific TCR, and CCL2 also dose-dependently augmented WT1 epitope-responsive IFN-γ production and CD107a expression mediated by these double gene-modifiedCD3+ T cells. Conclusion/Significance Introduction of the CCL2/CCR2 axis successfully potentiated in vivo anti-lung cancer

  11. Crystal structure and chemistry of lithium-bearing trioctahedral micas-3T

    USGS Publications Warehouse

    Brigatti, M.F.; Kile, D.E.; Poppi, L.

    2003-01-01

    Chemical analyses and crystal structure refinements were performed on lithian siderophyllite-3T crystals from granitic pegmatites of the anorogenic Pikes Peak batholith (Colorado) to characterize the crystal chemistry and relations with trioctahedral lithium-bearing micas showing different stacking sequences. Chemical data show that the studied samples fall on the siderophyllite-polylithionite join, closer to the siderophyllite end-member. Single-crystal X-ray refinements were carried out on three samples (two of which were taken from core and rim of the same crystal) in space-group P31 12 (the agreement factor, Robs, varies between 0.034 and 0.036). Mean bond distances and mean electron counts of M1, M2 and M3 octahedral sites indicate an ordered cation distribution with M1 and M3 positions substantially larger than M2. In the sample with the largest iron content, the M2 mean electron count increases as well as the mean distance, whereas remains smaller than or . The tetrahedral cation-oxygen atom mean distances range from 1.614 to 1.638 A and from 1.663 to 1.678 A for T1 and T2 sites, respectively, being consistent with Al3+ enrichment in the T2 sites. The tetrahedral rotation angle, α, is generally small (3.1 ≤ α ≤ 4.6) and decreases with siderophyllite content. As Fe increases, the T1 tetrahedron becomes flatter (112.4 ≤ t1 ≤ 110.5??), whereas T2 tetrahedron distortion appears unchanged (110.7 ≤ T2 ≤ 110.9).

  12. New results from T2K

    NASA Astrophysics Data System (ADS)

    Longhin, A.

    2017-12-01

    The T2K experiment is a 295-km long-baseline neutrino experiment in Japan employing an off-axis muon neutrino beam with a 0.6 GeV peak energy. The beam, produced from 30-GeV protons at the J-PARC complex on the Pacific coast, is directed to the Super-Kamiokande detector. T2K released the first long-baseline measurement of a nonzero value for the θ13 mixing parameter through the observation of electron neutrino appearance (vµ → ve) and produced the most precise measurement of θ23 through the observation of muon neutrino disappearance (vµ → vµ). T2K data, in combination with reactor experiments, also excludes at 90% C.L. a significant region of the Dirac CP phase: δCP < -3.02(-1.87) and δCP > -0.49(-0.98) for the normal (inverted) hierarchy. A full joint appearance and disappearance fit including both neutrino (7×1020 protons on target, PoT) and anti-neutrino (4 × 1020 PoT) data and, for the first time, a constraint from water target data in the near detector, is presented yielding improved sensitivity on δCP and improved precision on sin2 2θ23 and the atmospheric mass splitting.

  13. T2-mapping of the sacroiliac joints at 1.5 Tesla: a feasibility and reproducibility study.

    PubMed

    Albano, Domenico; Chianca, Vito; Cuocolo, Renato; Bignone, Rodolfo; Ciccia, Francesco; Sconfienza, Luca Maria; Midiri, Massimo; Brunetti, Arturo; Lagalla, Roberto; Galia, Massimo

    2018-04-20

    To evaluate the reproducibility of T2 relaxation time measurements of the sacroiliac joints at 1.5 T. Healthy volunteers underwent an oblique axial multislice multiecho spin-echo sequence of the sacroiliac joints at 1.5 T. Regions of interest were manually drawn using a dedicated software by two musculoskeletal radiologists to include the cartilaginous part of the sacroiliac joints. A senior radiologist performed the measurement twice, while a resident measured once. Intra- and inter-observer reproducibility was tested using the Bland-Altman method. Association between sex and T2 relaxation times was tested using the Mann-Whitney U test. Correlation between T2 relaxation times and body mass index (BMI) was tested using the Spearman's rho. Eighty sacroiliac joints of 40 subjects (mean age: 28 ± 4.8 years, range: 20-43; mean BMI: 23.3 ± 3.1, range: 18.9-30) were imaged. The mean T2 values obtained by the senior radiologist in the first series of measurements were 42 ± 4.4 ms, whereas in the second series were 40.7 ± 4.5 ms. The mean T2 values obtained by the radiology resident were 41.1 ± 4.2 ms. Intra-observer reproducibility was 88% (coefficient of repeatability = 3.8; bias = 1.28; p < .001), while inter-observer reproducibility was 86% (4.7; -.88; p < .001). There was significant association between sex and T2 relaxation times (p = .024) and significant inverse correlation between T2 relaxation times and BMI (r = -.340, p = .002). The assessment of T2 relaxation time measurements of sacroiliac joints seems to be highly reproducible at 1.5 T. Further studies could investigate the potential clinical application of this tool in the sacroiliac joints.

  14. Single-Chip T/R Module for 1.2 GHz

    NASA Technical Reports Server (NTRS)

    Moussessian, Alina; Mojarradi, Mohammad; Johnson, Travis; Davis, John; Grigorian, Edwin; Hoffman, James; Caro, Edward; Kuhn, William

    2006-01-01

    control line RX/TX (raised bar) is high, causing the field-effect transistor (FET) switch S1 to be closed, forming a parallel resonant tank circuit L1||C1. This circuit presents high impedance to the left of the antenna, so that the received signal is coupled to the LNA. At the same time, FET switches S2 and S3 are open, so that C2 is removed from the circuit (except for a small parasitic capacitance). The combination of L2 and C3 forms a matching network that transforms the antenna impedance of 50 ohms to a higher value from the perspective of the LNA input terminal. This transformation of impedance improves LNA noise figure by increasing the received voltage delivered to the input transistor. This allows lower transconductance and therefore a smaller transistor, which makes it possible to design the CMOS LNA for low power consumption. During transmission, the voltage on control line RX/TX (raised bar) is low, causing switch S1 to be open. In this configuration, the combination of L1 and C1 transforms the antenna impedance to a lower value from the perspective of the PA. This low impedance is helpful in producing a relatively high output power compatible with the low CMOS operating potential. At the same time, switches S2 and S3 are closed, forming the parallel resonant tank circuit L2||C2. This circuit presents high impedance to the right of the antenna, directing the PA output signal to the antenna and away from the LNA. During this time, S3 presents a short circuit across the LNA input terminals to guarantee that the voltage seen by the LNA is small enough to prevent damage.

  15. Effect of impurities of selenium and iron on the Anderson localization of 1T-TaS 2

    NASA Astrophysics Data System (ADS)

    Ōnuki, Y.; Inada, R.; Tanuma, S.

    1980-01-01

    The temperature dependence of electrical resistivities θ( T) of 1T-TaS 2, 1T-TaS 2- xSe x and 1T-Fe xTa 1- xS 2 is found to be θ( T) ∝ exp( T0/ T) 1/n in the temperature range of 4 K to the measured lowest temperature, 0.1 K, showing the variable range hopping of Anderson localized states. The n-value is nearly 3 for selenium doping and nearly 2 for non-doping and iron doping. The positive magnetoresistance, which is sizable only in the temperature range of 2 K to 0.5 K in 1T-TaS 2, is found to be remarkably enhanced by the selenium doping, while the tendency is reversed by the iron doping.

  16. Stable 1T-phase MoS2 as an effective electron mediator promoting photocatalytic hydrogen production.

    PubMed

    Shi, Jian-Wen; Zou, Yajun; Ma, Dandan; Fan, Zhaoyang; Cheng, Linhao; Sun, Diankun; Wang, Zeyan; Niu, Chunming; Wang, Lianzhou

    2018-05-17

    Coupling two semiconductors together to construct a Z-scheme type photocatalytic system is an efficient strategy to solve the serious recombination challenge of photogenerated electrons and holes. In this work, we develop a novel composite photocatalyst by sandwiching metallic 1T-phase MoS2 nanosheets between MoO3 and g-C3N4 (MoO3/1T-MoS2/g-C3N4) for the first time. The metallic 1T-phase MoS2 acts as an efficient electron mediator between MoO3 and g-C3N4 to construct an all-solid-state Z-scheme photocatalytic system, resulting in a highly-efficient spatial charge separation and transfer process. Benefiting from this, the newly developed MoO3/1T-MoS2/g-C3N4 exhibits a drastically enhanced photocatalytic H2 evolution rate of 513.0 μmol h-1 g-1 under visible light irradiation (>420 nm), which is nearly 12 times higher than that of the pure g-C3N4 (39.5 μmol h-1 g-1), and 3.5 times higher than that of MoO3/g-C3N4 (145.7 μmol h-1 g-1). More importantly, the originally unstable 1T-phase MoS2 becomes very stable in MoO3/1T-MoS2/g-C3N4 because of the sandwich structure where 1T-phase MoS2 is protected by MoO3 and g-C3N4, which endows the photocatalyst with excellent photostability. It is believed that this study will provide new insights into the design of efficient and stable Z-scheme heterostructures for photocatalytic applications.

  17. Aspartame downregulates 3T3-L1 differentiation.

    PubMed

    Pandurangan, Muthuraman; Park, Jeongeun; Kim, Eunjung

    2014-10-01

    Aspartame is an artificial sweetener used as an alternate for sugar in several foods and beverages. Since aspartame is 200 times sweeter than traditional sugar, it can give the same level of sweetness with less substance, which leads to lower-calorie food intake. There are reports that consumption of aspartame-containing products can help obese people lose weight. However, the potential role of aspartame in obesity is not clear. The present study investigated whether aspartame suppresses 3T3-L1 differentiation, by downregulating phosphorylated peroxisome proliferator-activated receptor γ (p-PPARγ), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1), which are critical for adipogenesis. The 3T3-L1 adipocytes were cultured and differentiated for 6 d in the absence and presence of 10 μg/ml of aspartame. Aspartame reduced lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. qRT-PCR analysis showed that the PPARγ, FABP4, and C/EBPα mRNA expression was significantly reduced in the aspartame-treated adipocytes. Western blot analysis showed that the induction of p-PPARγ, PPARγ, SREBP1, and adipsin was markedly reduced in the aspartame-treated adipocytes. Taken together, these data suggest that aspartame may be a potent substance to alter adipocyte differentiation and control obesity.

  18. Revisiting the human polypeptide GalNAc-T1 and T13 paralogs

    PubMed Central

    Festari, María Florencia; Trajtenberg, Felipe; Berois, Nora; Pantano, Sergio; Revoredo, Leslie; Kong, Yun; Solari-Saquieres, Patricia; Narimatsu, Yoshiki; Freire, Teresa; Bay, Sylvie; Robello, Carlos; Bénard, Jean; Gerken, Thomas A; Clausen, Henrik; Osinaga, Eduardo

    2017-01-01

    Polypeptide GalNAc-transferases (GalNAc-Ts) constitute a family of 20 human glycosyltransferases (comprising 9 subfamilies), which initiate mucin-type O-glycosylation. The O-glycoproteome is thought to be differentially regulated via the different substrate specificities and expression patterns of each GalNAc-T isoforms. Here, we present a comprehensive in vitro analysis of the peptide substrate specificity of GalNAc-T13, showing that it essentially overlaps with the ubiquitous expressed GalNAc-T1 isoform found in the same subfamily as T13. We have also identified and partially characterized nine splice variants of GalNAc-T13, which add further complexity to the GalNAc-T family. Two variants with changes in their lectin domains were characterized by in vitro glycosylation assays, and one (Δ39Ex9) was inactive while the second one (Ex10b) had essentially unaltered activity. We used reverse transcription-polymerase chain reaction analysis of human neuroblastoma cell lines, normal brain and a small panel of neuroblastoma tumors to demonstrate that several splice variants (Ex10b, ΔEx9, ΔEx2-7 and ΔEx6/8-39bpEx9) were highly expressed in tumor cell lines compared with normal brain, although the functional implications remain to be unveiled. In summary, the GalNAc-T13 isoform is predicted to function similarly to GalNAc-T1 against peptide substrates in vivo, in contrast to a prior report, but is unique by being selectively expressed in the brain. PMID:27913570

  19. T1ρ is superior to T2 mapping for the evaluation of articular cartilage denaturalization with osteoarthritis: radiological-pathological correlation after total knee arthroplasty.

    PubMed

    Takayama, Yukihisa; Hatakenaka, Masamitsu; Tsushima, Hidetoshi; Okazaki, Ken; Yoshiura, Takashi; Yonezawa, Masato; Nishikawa, Kei; Iwamoto, Yukihide; Honda, Hiroshi

    2013-04-01

    We compared the diagnostic performance of T1ρ and T2 mappings in the evaluation of denatured articular cartilage with osteoarthritis of the knee. 2D-Sagittal T1ρ and T2 mappings of the knee were obtained from 16 patients before total knee arthroplasty. After surgery, specimens of the femur and tibia were regionally segmented according to a 5-point scale of the severity of denaturalization. The T1ρ and T2 values in the full thickness of the articular cartilage in each region were measured by two observers. The two mappings were compared for their ability to differentiate between normal and denatured articular cartilage and also for their usefulness in grading the severity of the denaturalization using the area under receiver operating characteristic curves (Az). A p<0.05 was considered significant for each analysis. The T1ρ mapping showed a significantly higher Az value than the T2 mapping for the differentiation between normal and denatured articular cartilage (p<0.05). Regarding the assessment of the severity of denaturalization, T1ρ mapping could differentiate between normal and mild denaturalization (p<0.05), but T2 mapping could not. However, there were no significant differences between the two mappings in the discrimination of mild versus moderate denaturalization or of moderate versus severe denaturalization. The two observers showed good agreement in the results (intraclass correlation coefficient=0.81 for T1ρ and 0.92 for T2). T1ρ mapping is superior to T2 mapping for the evaluation of denatured articular cartilage with osteoarthritis of the knee. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

    NASA Astrophysics Data System (ADS)

    Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

    2018-04-01

    Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

  1. 1+γδT, early cardiac infiltrated innate population dominantly producing IL-4, protect mice against CVB3 myocarditis by modulating IFNγ+ T response.

    PubMed

    Wan, Fangfang; Yan, Kepeng; Xu, Dan; Qian, Qian; Liu, Hui; Li, Min; Xu, Wei

    2017-01-01

    Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1 + γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1 + γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT. We found that Vγ1 + γδT cells infiltration peaked in the heart at day3 post CVB3 infection and constituted a minor source of IFN-γ but major producers for early IL-4. Vγ1γδT cells were activated earlier holding a higher IL-4-producing efficiency than CD4 + Th cells in the heart. Depletion of Vγ1 + γδT resulted in a significantly exacerbated cardiac infiltration, increased T, macrophage and neutrophil population in heart homogenates and worse cardiomyopathy; which was accompanied by a significant expansion of peripheral IFNγ + CD4+ and CD8+T cells. Neutralization of IL-4 in mice resulted in an exacerbated acute myocarditis confirming the IL-4-mediated protective mechanism of Vγ1. Our findings identify a unique property of Vγ1 + γδT cells as one dominant early producers of IL-4 upon CVB3 acute infection which is a key mediator to protect mice against acute myocarditis by modulating IFNγ-secreting T response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Mn(II) based T1 and T2 potential MRI contrast agent appended with tryptamine: Recognition moiety for Aβ-plaques.

    PubMed

    Rastogi, Neeraj; Tyagi, Nidhi; Singh, Ovender; Hemanth Kumar, B S; Singh, Udai P; Ghosh, Kaushik; Roy, Raja

    2017-12-01

    We report the synthesis and characterization of manganese(II) complexes having pentadentate ligands L 1 (2,6-bis(1-(2-phenyl-2-(pyridin-2-yl)hydrazono)ethyl)pyridine), L 2 (methyl 2,6-bis((E)-1-(2-phenyl-2-(pyridin-2yl)hydrazono)ethyl)isonicotinate), L 3 (N-(2-(1H-indol-3-yl)ethyl)-2,6-bis((E)-1-(2-phenyl-2-(pyridin2yl)hydrazono)ethyl)isonicotiamide) and their application as dual contrast agents for simultaneous T 1 and T 2 weighted magnetic resonance imaging. Single crystal analysis of all the complexes [Mn II L 1 , Mn II L 2 and Mn II L 3 ] confirm the formation of novel seven-coordinate manganese complexes with an inner sphere water and perchlorate ion. The Magnetic Resonance Imaging (MRI) contrast agent [MnL 2 ] was further modified by incorporating tryptamine as a binding moiety specific to Amyloid Beta-fibrils (Aβ-fibrils) in Alzhiemer's disease (AD) and it's in vitro evaluation for specific binding with Aβ-fibrils indicated as a bio-marker of AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. T(T,4He)2n and 3He(3He,4He)2p Reactions and the Energy Dependence of Their Mechanisms

    NASA Astrophysics Data System (ADS)

    Bacher, Andrew; McNabb, Dennis; Brune, Carl; Sayre, Dan; Hale, Gerry; Frenje, Johan; Gatu Johnson, Maria

    2015-10-01

    We have studied the T(T,alpha)2n reaction because it is the charge symmetric analog to the 3He(3He,alpha)2p reaction which completes the most direct mode of the p-p chain in stellar interiors. These reactions lead to three-body final states whose energy spectrum shapes are dominated by the strong nucleon-alpha interaction and the weaker nucleon-nucleon interaction. These experiments were done at OMEGA at the University of Rochester and at the NIF at Lawrence Livermore Lab. We will focus on two features: (1) the excitation energy dependence of the reaction mechanism and (2) the center-of-mass energy dependence of the reaction mechanism. At stellar energies (OMEGA and the NIF) we find that the shape of the neutron spectrum peaks in the middle. The n-alpha 1/2-excited state is about two times stronger than the n-alpha 3/2-ground state. For the 3He+3He reaction (at CalTech), the proton spectrum peaks at the high end. The p-alpha 3/2-state is about two times stronger than the 1/2-state. This difference in the spectrum shape is explained by theoretical models which include the interference between the two identical fermions in the final state. At CalTech we have angular distributions of the 3He+3He reaction from 2 MeV to 18 MeV. We see the p-wave strength increasing.

  4. Hippocampal gene expression of deiodinases 2 and 3 and effects of 3,5-diiodo-L-thyronine T2 in mouse depression paradigms.

    PubMed

    Markova, Natalyia; Chernopiatko, Anton; Schroeter, Careen A; Malin, Dmitry; Kubatiev, Aslan; Bachurin, Sergey; Costa-Nunes, João; Steinbusch, Harry M W; Strekalova, Tatyana

    2013-01-01

    Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3',5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1,500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated.

  5. Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM.

    PubMed

    Jacober, S J; Rosenstock, J; Bergenstal, R M; Prince, M J; Qu, Y; Beals, J M

    2014-04-01

    The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings. Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM. Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients. In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.

  6. In Vitro Selective Anti-Proliferative Effect of Zinc Oxide Nanoparticles Against Co-Cultured C2C12 Myoblastoma Cancer and 3T3-L1 Normal Cells.

    PubMed

    Chandrasekaran, Murugesan; Pandurangan, Muthuraman

    2016-07-01

    The zinc oxide (ZnO) nanoparticle has been widely used in biomedical applications and cancer therapy and has been reported to induce a selective cytotoxic effect on cancer cell proliferation. The present study investigated the cytotoxicity of ZnO nanoparticles against co-cultured C2C12 myoblastoma cancer cells and 3T3-L1 adipocytes. Our results showed that the ZnO nanoparticles could be cytotoxic to C2C12 myoblastoma cancer cells than 3T3-L1 cells. The messenger RNA (mRNA) expressions of p53 and bax were significantly increased 114.3 and 118.2 % in the C2C12 cells, whereas 42.5 and 40 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was reduced 38.2 and 28.5 % in the C2C12 and 3T3-L1 cells, respectively, whereas the mRNA expression of caspase-3 was increased 80.7 and 51.6 % in the C2C12 and 3T3-L1 cells, respectively. The protein expressions of p53, bax, and caspase-3 were significantly increased 40, 81.8, and 80 % in C2C12 cells, whereas 20.3, 28.2, and 37.9 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was significantly reduced 32.2 and 22.7 % in C2C12 and 3T3-L1 cells, respectively. Caspase-3 enzyme activity and reactive oxygen species (ROS) were increased in co-cultured C2C12 cells compared to 3T3-L1 cells. Taking all these data together, it may suggest that ZnO nanoparticles severely induce apoptosis in C2C12 myoblastoma cancer cells than 3T3-L1 cells.

  7. Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators.

    PubMed

    Sørensen, Rikke Baek; Hadrup, Sine Reker; Svane, Inge Marie; Hjortsø, Mads Christian; Thor Straten, Per; Andersen, Mads Hald

    2011-02-17

    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We show that the presence of such IDO-specific CD8(+) T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO(+) suppressive cells. This had profound effects on the balance between interleukin-17 (IL-17)-producing CD4(+) T cells and regulatory T cells. Furthermore, this caused an increase in the production of the proinflammatory cytokines IL-6 and tumor necrosis factor-α while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (ie, the TLR9 ligand cytosine-phosphate-guanosine, soluble cytotoxic T lymphocyte-associated antigen 4, or interferon γ) induced IDO-specific T cells among peripheral blood mononuclear cells from patients with cancer as well as healthy donors. In the clinical setting, IDO may serve as an important and widely applicable target for immunotherapeutic strategies in which IDO plays a significant regulatory role. We describe for the first time effector T cells with a general regulatory function that may play a vital role for the mounting or maintaining of an effective adaptive immune response. We suggest terming such effector T cells "supporter T cells."

  8. Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.

    PubMed

    Chimote, Ameet A; Hajdu, Peter; Kucher, Vladimir; Boiko, Nina; Kuras, Zerrin; Szilagyi, Orsolya; Yun, Yeo-Heung; Conforti, Laura

    2013-12-15

    Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility. Adenosine selectively inhibited KCa3.1, but not Kv1.3 and TRPM7, in activated human T cells. This effect of adenosine was mainly mediated by A2A receptors, as KCa3.1 inhibition was reversed by SCH58261 (selective A2A receptor antagonist), but not by MRS1754 (A2B receptor antagonist), and it was mimicked by the A2A receptor agonist CGS21680. Furthermore, it was mediated by the cAMP/protein kinase A isoform (PKAI) signaling pathway, as adenylyl-cyclase and PKAI inhibition prevented adenosine effect on KCa3.1. The functional implication of the effect of adenosine on KCa3.1 was determined by measuring T cell motility on ICAM-1 surfaces. Adenosine and CGS21680 inhibited T cell migration. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Furthermore, the effect of adenosine on cell migration was abolished by pre-exposure to TRAM-34. Additionally, adenosine suppresses IL-2 secretion via KCa3.1 inhibition. Our data indicate that adenosine inhibits KCa3.1 in human T cells via A2A receptor and PKAI, thereby resulting in decreased T cell motility and cytokine release. This mechanism is likely to contribute to decreased immune surveillance in solid tumors.

  9. Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Masiello, Lisa M.; Fotos, Joseph S.; Galileo, Deni S.

    2006-07-01

    Lysophosphatidic acid (LPA) is a bioactive lipid that has pleiotropic effects on a variety of cell types and enhances the migration of endothelial and cancer cells, but it is not known if this lipid can alter osteoblast motility. We performed transwell migration assays using MC3T3-E1 osteoblastic cells and found LPA to be a potent chemotactic agent. Quantitative time-lapse video analysis of osteoblast migration after wounds were introduced into cell monolayers indicated that LPA stimulated both migration velocity and the average migration distance per cell. LPA also elicited substantial changes in cell shape and actin cytoskeletal structure; lipid-treated cells contained fewermore » stress fibers and displayed long membrane processes that were enriched in F-actin. Quantitative RT-PCR analysis showed that MC3T3-E1 cells express all four known LPA-specific G protein-coupled receptors (LPA1-LPA4) with a relative mRNA abundance of LPA1 > LPA4 > LPA2 >> LPA3. LPA-induced changes in osteoblast motility and morphology were antagonized by both pertussis toxin and Ki16425, a subtype-specific blocker of LPA1 and LPA3 receptor function. Cell migration in many cell types is linked to changes in intracellular Ca2+. Ki16425 also inhibited LPA-induced Ca2+ signaling in a dose-dependent manner, suggesting a link between LPA-induced Ca2+ transients and osteoblast chemotaxis. Our data show that LPA stimulates MC3T3-E1 osteoblast motility via a mechanism that is linked primarily to the G protein-coupled receptor LPA1.« less

  10. Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

    PubMed

    Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

    2016-04-01

    To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. HIV-1 Triggers WAVE2 Phosphorylation in Primary CD4 T Cells and Macrophages, Mediating Arp2/3-dependent Nuclear Migration*

    PubMed Central

    Spear, Mark; Guo, Jia; Turner, Amy; Yu, Dongyang; Wang, Weifeng; Meltzer, Beatrix; He, Sijia; Hu, Xiaohua; Shang, Hong; Kuhn, Jeffrey; Wu, Yuntao

    2014-01-01

    The human immunodeficiency virus type 1 (HIV-1) initiates receptor signaling and early actin dynamics during viral entry. This process is required for viral infection of primary targets such as resting CD4 T cells. WAVE2 is a component of a multiprotein complex linking receptor signaling to dynamic remodeling of the actin cytoskeleton. WAVE2 directly activates Arp2/3, leading to actin nucleation and filament branching. Although several bacterial and viral pathogens target Arp2/3 for intracellular mobility, it remains unknown whether HIV-1 actively modulates the Arp2/3 complex through virus-mediated receptor signal transduction. Here we report that HIV-1 triggers WAVE2 phosphorylation at serine 351 through gp120 binding to the chemokine coreceptor CXCR4 or CCR5 during entry. This phosphorylation event involves both Gαi-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages. We further demonstrate that inhibition of WAVE2-mediated Arp2/3 activity through stable shRNA knockdown of Arp3 dramatically diminished HIV-1 infection of CD4 T cells, preventing viral nuclear migration. Inhibition of Arp2/3 through a specific inhibitor, CK548, also drastically inhibited HIV-1 nuclear migration and infection of CD4 T cells. Our results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission. PMID:24415754

  12. HIV-1 triggers WAVE2 phosphorylation in primary CD4 T cells and macrophages, mediating Arp2/3-dependent nuclear migration.

    PubMed

    Spear, Mark; Guo, Jia; Turner, Amy; Yu, Dongyang; Wang, Weifeng; Meltzer, Beatrix; He, Sijia; Hu, Xiaohua; Shang, Hong; Kuhn, Jeffrey; Wu, Yuntao

    2014-03-07

    The human immunodeficiency virus type 1 (HIV-1) initiates receptor signaling and early actin dynamics during viral entry. This process is required for viral infection of primary targets such as resting CD4 T cells. WAVE2 is a component of a multiprotein complex linking receptor signaling to dynamic remodeling of the actin cytoskeleton. WAVE2 directly activates Arp2/3, leading to actin nucleation and filament branching. Although several bacterial and viral pathogens target Arp2/3 for intracellular mobility, it remains unknown whether HIV-1 actively modulates the Arp2/3 complex through virus-mediated receptor signal transduction. Here we report that HIV-1 triggers WAVE2 phosphorylation at serine 351 through gp120 binding to the chemokine coreceptor CXCR4 or CCR5 during entry. This phosphorylation event involves both Gαi-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages. We further demonstrate that inhibition of WAVE2-mediated Arp2/3 activity through stable shRNA knockdown of Arp3 dramatically diminished HIV-1 infection of CD4 T cells, preventing viral nuclear migration. Inhibition of Arp2/3 through a specific inhibitor, CK548, also drastically inhibited HIV-1 nuclear migration and infection of CD4 T cells. Our results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission.

  13. Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dong, Yan; Hirane, Miku; Araki, Mutsumi

    2014-04-04

    Highlights: • LPA{sub 5} inhibits the cell growth and motile activities of 3T3 cells. • LPA{sub 5} suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA{sub 5} on the cell motile activities inhibited by LPA{sub 1} in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA{sub 5} in 3T3 cells. • LPA signaling via LPA{sub 5} acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA{sub 1}–LPA{sub 6}) mediates a variety of biological functions, including cellmore » migration. Recently, we have reported that LPA{sub 1} inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA{sub 5} in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA{sub 1} and LPA{sub 5} on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA{sub 5} may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA{sub 1}.« less

  14. Variable flip angle 3D ultrashort echo time (UTE) T1 mapping of mouse lung: A repeatability assessment.

    PubMed

    Alamidi, Daniel F; Smailagic, Amir; Bidar, Abdel W; Parker, Nicole S; Olsson, Marita; Hockings, Paul D; Lagerstrand, Kerstin M; Olsson, Lars E

    2018-03-08

    Lung T 1 is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T 1 mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy. To evaluate the feasibility of regional lung T 1 quantification with VFA 3D-UTE and to investigate long- and short-term T 1 repeatability in the lungs of naive mice. Prospective preclinical animal study. Eight naive mice and phantoms. 3D free-breathing radial UTE (8 μs) at 4.7T. VFA 3D-UTE T 1 calculations were validated against T 1 values measured with inversion recovery (IR) in phantoms. Lung T 1 and proton density (S 0 ) measurements of whole lung and muscle were repeated five times over 1 month in free-breathing naive mice. Two consecutive T 1 measurements were performed during one of the imaging sessions. Agreement in T 1 between VFA 3D-UTE and IR in phantoms was assessed using Bland-Altman and Pearson 's correlation analysis. The T 1 repeatability in mice was evaluated using coefficient of variation (CV), repeated-measures analysis of variance (ANOVA), and paired t-test. Good T 1 agreement between the VFA 3D-UTE and IR methods was found in phantoms. T 1 in lung and muscle showed a 5% and 3% CV (1255 ± 63 msec and 1432 ± 42 msec, respectively, mean ± SD) with no changes in T 1 or S 0 over a month. Consecutive measurements resulted in an increase of 2% in both lung T 1 and S 0 . VFA 3D-UTE shows promise as a reliable T 1 mapping method that enables full lung coverage, high signal-to-noise ratio (∼25), and spatial resolution (300 μm) in freely breathing animals. The precision of the VFA 3D-UTE method will enable better design and powering of studies. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

  15. T-T Neutron Spectrum from Inertial Confinement Implosions

    NASA Astrophysics Data System (ADS)

    Bacher, A. D.; Casey, D. T.; Frenje, J. A.; Gatu Johnson, M. J.; Manuel, M.; Sinenian, N.; Zylstra, A. B.; Séguin, F. H.; Li, C. K.; Petrasso, R. D.; Glebov, V. Yu; Radha, P. B.; Meyerhofer, D. D.; Sangster, T. C.; McNabb, D. P.; Amendt, P. A.; Boyd, R. N.; Caggiano, J. A.; Hatchett, S. P.; Pino, J. E.; Quaglioni, S.; Rygg, J. R.; Thompson, I. J.; Herrmann, H. W.; Kim, Y. H.

    2013-08-01

    A new technique that uses inertial confinement implosions for measuring low-energy nuclear reactions important to nuclear astrophysics is described. Simultaneous measurements of n-D and n-T elastic scattering at 14.1 MeV using deuterium-tritium gas-filled capsules provide a proof of principle for this technique. Measurements have been made of D(d,p)T (dd) and T(t,2n)4He (tt) reaction yields relative to the D(t,n)4He (dt) reaction yield for deuterium-tritium mixtures with f T / f D between 0.62 and 0.75 and for a wide range of ion temperatures to test our understanding of the implosion processes. Measurements of the shape of the neutron spectrum from the T(t,2n)4He reaction have been made for each of these target configurations.

  16. Non-invasive evaluation of blood oxygen saturation and hematocrit from T1 and T2 relaxation times: In-vitro validation in fetal blood.

    PubMed

    Portnoy, Sharon; Seed, Mike; Sled, John G; Macgowan, Christopher K

    2017-12-01

    We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO 2 ) from measurements of its T 1 and T 2 relaxation times. Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO 2 in terms of R 1 and R 2 . Resulting solutions for Hct and sO 2 are the roots of cubic polynomials. Feasibility of the method was established by comparison of Hct and sO 2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T 1 , T 2 measurement uncertainty on precision of Hct and sO 2 estimates. Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO 2 ). Considering the combined effects of biological variability and random measurement noise, we estimate a typical uncertainty of ±0.1 for Hct, sO 2 estimates. Results demonstrate accurate quantification of Hct and sO 2 from T 1 and T 2 . This method is applicable to noninvasive fetal vessel oximetry-an application where existing oximetry devices are unusable or require risky blood-sampling procedures. Magn Reson Med 78:2352-2359, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  17. RETRACTED: Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population.

    PubMed

    Zhong, Weiqiang; Jiang, Zongpei; Zhou, Tian-Biao

    2015-12-01

    .1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314566221, first published on February 1, 2015 doi: 10.1177/1470320314566221 Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang, and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population Journal of Renin-Angiotensin-Aldosterone System March 2015 16: 165-171, first published on November 14, 2014 doi: 10.1177/1470320314557849 Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang, and Tian-Biao Zhou Association of aldosterone synthase (CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy Journal of Renin-Angiotensin-Aldosterone System September 2015 16: 660-665, first published on August 20, 2014 doi: 10.1177/1470320314524011.

  18. Compressive force induces osteoclast differentiation via prostaglandin E(2) production in MC3T3-E1 cells.

    PubMed

    Sanuki, Rina; Shionome, Chieko; Kuwabara, Akiko; Mitsui, Narihiro; Koyama, Yuki; Suzuki, Naoto; Zhang, Fan; Shimizu, Noriyoshi; Maeno, Masao

    2010-04-01

    In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We previously showed that compressive force (CF) controls bone formation by stimulating the production of PGE(2) and Ep2 and/or Ep4 receptors in osteoblasts. The present study was undertaken to examine the effect of CF on the production of PGE(2), cyclooxygenase-2 (COX-2), macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) using osteoblastic MC3T3-E1 cells and to examine the indirect effect of CF on osteoclast differentiation using RAW264.7 cells as osteoclast precursors. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 3.0 g/cm(2)) for 24 hr, and PGE(2) production was determined using ELISA. The expression of COX-2, M-CSF, RANKL, and OPG genes and proteins was determined using real-time PCR and ELISA, respectively. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of RAW 264.7 cells cultured for 10 days with conditioned medium from CF-treated MC3T3-E1 cells and soluble RANKL. As CF increased, PGE(2) production and the expression of COX-2, M-CSF, and RANKL increased, whereas OPG expression decreased. The number of TRAP-positive cells increased as CF increased. Celecoxib, a specific inhibitor of COX-2, blocked the stimulatory effect of CF on TRAP staining and the production of PGE(2), M-CSF, RANKL, and OPG. These results suggest that CF induces osteoclast differentiation by increasing M-CSF production and decreasing OPG production via PGE(2) in osteoblasts.

  19. Induction and prevention of low-T3 syndrome in exercising women.

    PubMed

    Loucks, A B; Callister, R

    1993-05-01

    To investigate the influence of exercise on thyroid metabolism, 46 healthy young regularly menstruating sedentary women were randomly assigned to a 3 x 2 experimental design of aerobic exercise and energy availability treatments. Energy availability was defined as dietary energy intake minus energy expenditure during exercise. After 4 days of treatments, low energy availability (8 vs. 30 kcal.kg body wt-1.day-1) had reduced 3,5,3'-triiodothyronine (T3) by 15% and free T3 (fT3) by 18% and had increased thyroxine (T4) by 7% and reverse T3 (rT3) by 24% (all P < 0.01), whereas free T4 (fT4) was unchanged (P = 0.08). Exercise quantity (0 vs. 1,300 kcal/day) and intensity (40 vs. 70% of aerobic capacity) did not affect any thyroid hormone (all P > 0.10). That is, low-T3 syndrome was induced by the energy cost of exercise and was prevented in exercising women by increasing dietary energy intake. Selective observation of low-T3 syndrome in amenorrheic and not in regularly menstruating athletes suggests that exercise may compromise the availability of energy for reproductive function in humans. If so, athletic amenorrhea might be prevented or reversed through dietary reform without reducing exercise quantity or intensity.

  20. T2* measurements of 3-T MRI with ultrashort TEs: capabilities of pulmonary function assessment and clinical stage classification in smokers.

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Keiko; Takahashi, Masaya; Van Cauteren, Marc; Sugimura, Kazuro

    2011-08-01

    The purpose of this study was to determine the usefulness of MRI with ultrashort TEs on a 3-T system and of thin-section MDCT for pulmonary function assessment and clinical stage classification of chronic obstructive pulmonary disease (COPD) in smokers. Forty smokers (24 men and 16 women; mean age ± SD, 68.0 ± 9.3 years) underwent MRI with ultrashort TEs and thin-section MDCT. Pulmonary function testing was also performed to determine the following: the ratio of forced expiratory volume in 1 second to forced vital capacity (percentage predicted) (FEV(1/)FVC%), percentage predicted forced expiratory volume in 1 second (%FEV(1)), and percentage predicted diffusing capacity of lung for carbon monoxide corrected for alveolar volume (%DLCO/V(A)). All subjects were classified into one of four groups as follows: smokers without COPD, with mild COPD, with moderate COPD, and with severe or very severe COPD. T2(*) maps were expressed using proprietary software. Regional T2(*) values were determined by region of interest measurements and were averaged to determine a mean T2(*) value for each subject. CT-based functional lung volume and the ratio of the wall area to the total airway area were also determined. All indexes were statistically correlated with pulmonary function parameters. Then, all indexes were compared among all groups by means of Tukey's honest significance test. All indexes had significant correlation with FEV(1)/FVC%, %FEV(1), and % DLCO/V(A) (p < 0.05). All indexes except WA% of smokers without COPD and smokers with mild COPD differed significantly from those of smokers with moderate COPD and smokers with severe or very severe COPD (p < 0.05). Moreover, the mean T2(*) value of the moderate COPD group was significantly different from that of the severe or very severe COPD group (p < 0.05). MRI with ultrashort TEs is potentially as useful as quantitatively assessed MDCT for pulmonary function loss assessment and clinical stage classification of COPD in

  1. Magnetic resonance measurement of muscle T2, fat-corrected T2 and fat fraction in the assessment of idiopathic inflammatory myopathies

    PubMed Central

    Yao, Lawrence; Yip, Adrienne L.; Shrader, Joseph A.; Mesdaghinia, Sepehr; Volochayev, Rita; Jansen, Anna V.; Miller, Frederick W.

    2016-01-01

    Objective. This study examines the utility of MRI, including T2 maps and T2 maps corrected for muscle fat content, in evaluating patients with idiopathic inflammatory myopathy. Methods. A total of 44 patients with idiopathic inflammatory myopathy, 18 of whom were evaluated after treatment with rituximab, underwent MRI of the thighs and detailed clinical assessment. T2, fat fraction (FF) and fat corrected T2 (fc-T2) maps were generated from standardized MRI scans, and compared with semi-quantitative scoring of short tau inversion recovery (STIR) and T1-weighted sequences, as well as various myositis disease metrics, including the Physician Global Activity, the modified Childhood Myositis Assessment Scale and the muscle domain of the Myositis Disease Activity Assessment Tool-muscle (MDAAT-muscle). Results. Mean T2 and mean fc-T2 correlated similarly with STIR scores (Spearman rs = 0.64 and 0.64, P < 0.01), while mean FF correlated with T1 damage scores (rs = 0.69, P < 0.001). Baseline T2, fc-T2 and STIR scores correlated significantly with the Physician Global Activity, modified Childhood Myositis Assessment Scale and MDAAT-muscle (rs range = 0.41–0.74, P < 0.01). The response of MRI measures to rituximab was variable, and did not significantly agree with a standardized clinical definition of improvement. Standardized response means for the MRI measures were similar. Conclusion. Muscle T2, fc-T2 and FF measurements exhibit content validity with reference to semi-quantitative scoring of STIR and T1 MRI, and also exhibit construct validity with reference to several myositis activity and damage measures. T2 was as responsive as fc-T2 and STIR scoring, although progression of muscle damage was negligible during the study. PMID:26412808

  2. Anti-Obesity Effects of Starter Fermented Kimchi on 3T3-L1 Adipocytes

    PubMed Central

    Lee, Kyung-Hee; Song, Jia-Le; Park, Eui-Seong; Ju, Jaehyun; Kim, Hee-Young; Park, Kun-Young

    2015-01-01

    The anti-obesity effects of starter (Leuconostoc mesenteroides+Lactobacillus plantarum) fermented kimchi on 3T3-L1 adipocyte were studied using naturally fermented kimchi (NK), a functional kimchi (FK, NK supplemented with green tea), and FK supplemented with added starters (FKS). Oil red O staining and cellular levels of triglyceride (TG) and glycerol were used to evaluate the in vitro anti-obesity effects of these kimchis in 3T3-L1 cells. The expressions of adipogenesis/lipogenesis-related genes of peroxisome proliferator-active receptor (PPAR)-γ, CCAAT/enhance-binding protein (C/EBP)-α, and fatty acid synthase (FAS) were determined by RT-PCR. Kimchis, especially FKS, markedly decreased TG levels and increased levels of intracellular glycerol and lipid lipolysis. In addition, FKS also reduced the mRNA levels of PPAR-γ, C/EBP-α, and FAS, which are related to adipogenesis/lipogenesis in 3T3-L1 cells. These results suggest the anti-obesity effects of FKS were to due to enhanced lipolysis and reduced adipogenesis/lipogenesis in 3T3-L1 adipocytes. PMID:26770918

  3. Women Transmits Type 2 Diabetes Mellitus (T2DM) More Than Men: Evidences from Parental Inheritance of T2DM Among Bahrainis.

    PubMed

    Al-Harbi, E M; Farid, E M; Darwish, A H; Gumaa, K A; Giha, H A

    2016-07-01

    Heritability in type 2 diabetes mellitus (T2DM) is observed but not well understood. In this study, family history and clinical/biochemical data from 789 Bahrainis (418 T2DM, 371 controls) was analyzed. Fasting blood glucose (FBG) and HbA1c were measured and angiotensin-converting enzyme (ACE) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms (SNPs) were analyzed. Patients compared to controls have higher proportions of diabetic mothers (50.2% vs. 32.7%, p=0.005), fathers (35.2% vs. 12.1%, p<0.001) and siblings (56% vs. 15.3%, p<0.001). The proportions of diabetic mothers was higher than the proportions of diabetic fathers among the patients (50.2% vs. 35.2%, p<0.001) and the controls (32.7% vs. 12.1%, p<0.001). Patients born to diabetic mothers compared to the other patients were smaller in age at the time of enrollment in this study (p=0.005), and at onset of T2DM (p<0.001), and also had higher FBG (p=0.033). Interestingly, the prevalence of T1DM was highest amongst the siblings of the controls compared to patients (p=0.04). Finally, the heterozygote I/D genotype of the ACE gene was over expressed in patients born to diabetic mothers when compared to patients born to diabetic fathers, p=0.007. there was strong clustering of T2DM in families, with significant dominant maternal role in transmission of T2DM and associated severity markers. Patients (T2DM) born to diabetic mothers were genetically and phenotypically different from the other patients. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Topographic Diagnosis of Craniopharyngiomas: The Accuracy of MRI Findings Observed on Conventional T1 and T2 Images.

    PubMed

    Prieto, R; Pascual, J M; Barrios, L

    2017-11-01

    The topography of craniopharyngiomas has proved fundamental in predicting the involvement of vital brain structures and the possibility of achieving a safe radical resection. Beyond the imprecise term "suprasellar," indiscriminately used for craniopharyngiomas, an accurate definition of craniopharyngioma topography should be assessed by preoperative MR imaging. The objective of this study was to investigate the MRI findings that help define craniopharyngioma topography. This study retrospectively investigated a cohort of 200 surgically treated craniopharyngiomas with their corresponding preoperative midsagittal and coronal conventional T1- and T2-weighted MR images, along with detailed descriptions of the surgical findings. Radiologic variables related to the occupation of the tumor of intracranial compartments and the distortions of anatomic structures along the sella turcica-third ventricle axis were analyzed and correlated with the definitive craniopharyngioma topography observed during the surgical procedures. A predictive model for craniopharyngioma topography was generated by multivariate analysis. Five major craniopharyngioma topographies can be defined according to the degree of hypothalamic distortion caused by the tumor: sellar-suprasellar, pseudointraventricular, secondary intraventricular, not strictly intraventricular, and strictly intraventricular. Seven key radiologic variables identified on preoperative MRI allowed a correct overall prediction of craniopharyngioma topography in 86% of cases: 1) third ventricle occupation, 2) pituitary stalk distortion, 3) relative level of the hypothalamus in relation to the tumor, 4) chiasmatic cistern occupation, 5) mammillary body angle, 6) type of chiasm distortion, and 7) tumor shape. Systematic assessment of these 7 variables on conventional preoperative T1 and T2 MRI is a useful and reliable method to ascertain individual craniopharyngioma topography. © 2017 by American Journal of Neuroradiology.

  5. [Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].

    PubMed

    Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J

    2018-02-07

    Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in

  6. Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kimira, Yoshifumi, E-mail: kimira@josai.ac.jp; Ogura, Kana; Taniuchi, Yuri

    Highlights: • Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization. • Pro-Hyp significantly increased alkaline phosphatase activity. • Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. - Abstract: Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. The objective of this study was to investigate the effects of Pro-Hyp on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. Addition of Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization but alkaline phosphatase activity was significantly increased. Furthermore, cells treated with Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. These results indicatemore » that Pro-Hyp promotes osteoblast differentiation. This study demonstrates for the first time that Pro-Hyp has a positive effect on osteoblast differentiation with upregulation of Runx2, Osterix, and Collα1 gene expression.« less

  7. Functional classification of memory CD8(+) T cells by CX3CR1 expression.

    PubMed

    Böttcher, Jan P; Beyer, Marc; Meissner, Felix; Abdullah, Zeinab; Sander, Jil; Höchst, Bastian; Eickhoff, Sarah; Rieckmann, Jan C; Russo, Caroline; Bauer, Tanja; Flecken, Tobias; Giesen, Dominik; Engel, Daniel; Jung, Steffen; Busch, Dirk H; Protzer, Ulrike; Thimme, Robert; Mann, Matthias; Kurts, Christian; Schultze, Joachim L; Kastenmüller, Wolfgang; Knolle, Percy A

    2015-09-25

    Localization of memory CD8(+) T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX3CR1 distinguishes memory CD8(+) T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX3CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8(+) T cells with effector function. We find CD62L(hi)CX3CR1(+) memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX3CR1(+) memory CD8(+) T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX3CR1-based functional classification will help to resolve the principles of protective CD8(+) T-cell memory.

  8. NKL homeobox gene activities in hematopoietic stem cells, T-cell development and T-cell leukemia.

    PubMed

    Nagel, Stefan; Pommerenke, Claudia; Scherr, Michaela; Meyer, Corinna; Kaufmann, Maren; Battmer, Karin; MacLeod, Roderick A F; Drexler, Hans G

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1). Interestingly, our data indicated downregulation of NKL homeobox gene transcripts in late progenitors and mature T-cells, a phenomenon which might explain the oncogenic impact of this group of genes in T-ALL. Using MSX1-expressing T-ALL cell lines as models, we showed that HHEX activates while HLX1, NKX2-3 and NKX3-1 repress MSX1 transcription, demonstrating the mutual regulation and differential activities of these homeobox genes. Analysis of a public T-ALL expression profiling data set comprising 117 patient samples identified 20 aberrantly activated members of the NKL subclass, extending the number of known NKL homeobox oncogene candidates. While 7/20 genes were also active during hematopoiesis, the remaining 13 showed ectopic expression. Finally, comparative analyses of T-ALL patient and cell line profiling data of NKL-positive and NKL-negative samples indicated absence of shared target genes but instead highlighted deregulation of apoptosis as common oncogenic effect. Taken together, we present a comprehensive survey of NKL homeobox genes in early hematopoiesis, T-cell development and T-ALL, showing that these genes generate an NKL-code for the diverse stages of lymphoid development which might be fundamental for regular differentiation.

  9. NKL homeobox gene activities in hematopoietic stem cells, T-cell development and T-cell leukemia

    PubMed Central

    Pommerenke, Claudia; Scherr, Michaela; Meyer, Corinna; Kaufmann, Maren; Battmer, Karin; MacLeod, Roderick A. F.; Drexler, Hans G.

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1). Interestingly, our data indicated downregulation of NKL homeobox gene transcripts in late progenitors and mature T-cells, a phenomenon which might explain the oncogenic impact of this group of genes in T-ALL. Using MSX1-expressing T-ALL cell lines as models, we showed that HHEX activates while HLX1, NKX2-3 and NKX3-1 repress MSX1 transcription, demonstrating the mutual regulation and differential activities of these homeobox genes. Analysis of a public T-ALL expression profiling data set comprising 117 patient samples identified 20 aberrantly activated members of the NKL subclass, extending the number of known NKL homeobox oncogene candidates. While 7/20 genes were also active during hematopoiesis, the remaining 13 showed ectopic expression. Finally, comparative analyses of T-ALL patient and cell line profiling data of NKL-positive and NKL-negative samples indicated absence of shared target genes but instead highlighted deregulation of apoptosis as common oncogenic effect. Taken together, we present a comprehensive survey of NKL homeobox genes in early hematopoiesis, T-cell development and T-ALL, showing that these genes generate an NKL-code for the diverse stages of lymphoid development which might be fundamental for regular differentiation. PMID:28151996

  10. T1-weighted brain imaging with a 32-channel coil at 3T using TurboFLASH BLADE compared with standard cartesian k-space sampling.

    PubMed

    Attenberger, Ulrike I; Runge, Val M; Williams, Kenneth D; Stemmer, Alto; Michaely, Henrik J; Schoenberg, Stefan O; Reiser, Maximilian F; Wintersperger, Bernd J

    2009-03-01

    Motion artifacts often markedly degrade image quality in clinical scans. The BLADE technique offers an alternative k-space sampling scheme reducing the effect of patient related motion on image quality. The purpose of this study is the comparison of imaging artifacts, signal-to-noise (SNR), and contrast-to-noise ratio (CNR) of a new turboFLASH BLADE k-space trajectory with the standard Cartesian k-space sampling for brain imaging, using a 32-channel coil at 3T. The results from 32 patients included after informed consent are reported. This study was performed with a 32-channel head coil on a 3T scanner. Sagittal and axial T1-weighted FLASH sequences (TR/TE 250/2.46 milliseconds, flip angle 70-degree), acquired with Cartesian k-space sampling and T1-weighted turboFLASH sequences (TR/TE/TIsag/TIax 3200/2.77/1144/1056 milliseconds, flip angle 20-degree), using PROPELLER (BLADE) k-space trajectory, were compared. SNR and CNR were evaluated using a paired student t test. The frequency of motion artifacts was assessed in a blinded read. To analyze the differences between both techniques a McNemar test was performed. A P value <0.05 was considered statistically significant. From the blinded read, the overall preference in terms of diagnostic image quality was statistically significant in favor of the BLADE turboFLASH data sets, compared with standard FLASH for both sagittal (P < 0.0001) and axial (P < 0.0001) planes. The frequency of motion artifacts from the scalp was higher for standard FLASH sequences than for BLADE sequences on both axial (47%, P < 0.0003) and sagittal (69%, P < 0.0001) planes. BLADE was preferred in 100% (sagittal plane) and 80% (axial plane) of in-patient data sets and in 68% (sagittal plane) and 73% (axial plane) of out-patient data sets.The BLADE T1 scan did have lower SNRmean (BLADEax 179 +/- 98, Cartesianax 475 +/- 145, BLADEsag 171 +/- 51, and Cartesiansag 697 +/- 129) with P values indicating accordingly a statistically significant difference

  11. Depletion of Saccharomyces cerevisiae tRNAHis Guanylyltransferase Thg1p Leads to Uncharged tRNAHis with Additional m5C

    PubMed Central

    Gu, Weifeng; Hurto, Rebecca L.; Hopper, Anita K.; Grayhack, Elizabeth J.; Phizicky, Eric M.

    2005-01-01

    The essential Saccharomyces cerevisiae tRNAHis guanylyltransferase (Thg1p) is responsible for the unusual G−1 addition to the 5′ end of cytoplasmic tRNAHis. We report here that tRNAHis from Thg1p-depleted cells is uncharged, although histidyl tRNA synthetase is active and the 3′ end of the tRNA is intact, suggesting that G−1 is a critical determinant for aminoacylation of tRNAHis in vivo. Thg1p depletion leads to activation of the GCN4 pathway, most, but not all, of which is Gcn2p dependent, and to the accumulation of tRNAHis in the nucleus. Surprisingly, tRNAHis in Thg1p-depleted cells accumulates additional m5C modifications, which are delayed relative to the loss of G−1 and aminoacylation. The additional modification is likely due to tRNA m5C methyltransferase Trm4p. We developed a new method to map m5C residues in RNA and localized the additional m5C to positions 48 and 50. This is the first documented example of the accumulation of additional modifications in a eukaryotic tRNA species. PMID:16135808

  12. Pre-treatment functional MRI of breast cancer: T2* evaluation at 3T and relationship to dynamic contrast-enhanced and diffusion-weighted imaging.

    PubMed

    Kousi, Evanthia; O'Flynn, Elizabeth A M; Borri, Marco; Morgan, Veronica A; deSouza, Nandita M; Schmidt, Maria A

    2018-05-31

    Baseline T2* relaxation time has been proposed as an imaging biomarker in cancer, in addition to Dynamic Contrast-Enhanced (DCE) MRI and diffusion-weighted imaging (DWI) parameters. The purpose of the current work is to investigate sources of error in T2* measurements and the relationship between T2* and DCE and DWI functional parameters in breast cancer. Five female volunteers and thirty-two women with biopsy proven breast cancer were scanned at 3T, with Research Ethics Committee approval. T2* values of the normal breast were acquired from high-resolution, low-resolution and fat-suppressed gradient-echo sequences in volunteers, and compared. In breast cancer patients, pre-treatment T2*, DCE MRI and DWI were performed at baseline. Pathologically complete responders at surgery and non-responders were identified and compared. Principal component analysis (PCA) and cluster analysis (CA) were performed. There were no significant differences between T2* values from high-resolution, low-resolution and fat-suppressed datasets (p > 0.05). There were not significant differences between baseline functional parameters in responders and non-responders (p > 0.05). However, there were differences in the relationship between T2* and contrast-agent uptake in responders and non-responders. Voxels of similar characteristics were grouped in 5 clusters, and large intra-tumoural variations of all parameters were demonstrated. Breast T2* measurements at 3T are robust, but spatial resolution should be carefully considered. T2* of breast tumours at baseline is unrelated to DCE and DWI parameters and contribute towards describing functional heterogeneity of breast tumours. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes.

    PubMed

    Ren, Rui; Chen, Zhufeng; Zhao, Xia; Sun, Tao; Zhang, Yuchao; Chen, Jie; Lu, Sumei; Ma, Wanshan

    2016-11-08

    Peroxisome proliferator-activated receptor γ (PPARγ) is a critical gene that regulates the function of adipocytes. Therefore, studies on the molecular regulation mechanism of PPARγ are important to understand the function of adipose tissue. Twist 1 is another important functional gene in adipose tissue, and hundreds of genes are regulated by Twist 1. The aim of this study was to investigate the regulation of Twist 1 and PPARγ expression in 3T3-L1 mature adipocytes. We induced differentiation in 3T3-L1 preadipocytes and examined alterations in Twist 1 and PPARγ expression. We used the PPARγ agonist pioglitazone and the PPARγ antagonist T0070907 to investigate the effect of PPARγ on Twist 1 expression. In addition, we utilized retroviral interference and overexpression of Twist 1 to determine the effects of Twist 1 on PPARγ expression. The expression levels of Twist 1 and PPARγ were induced during differentiation in 3T3-L1 adipocytes. Application of either a PPARγ agonist (pioglitazone) or antagonist (T0070907) influenced Twist 1 expression, with up-regulation of Twist 1 under pioglitazone (1 μM, 24 h) and down-regulation of Twist 1 under T0070907 (100 μM, 24 h) exposure. Furthermore, the retroviral interference of Twist 1 decreased the protein and mRNA expression of PPARγ, while Twist 1 overexpression had the opposite effect. There was a possible regulatory link between Twist 1 and PPARγ in 3T3-L1 mature adipocytes. This regulatory link enhanced the regulation of PPARγ and may be a functional mechanism of Twist 1 regulation of adipocyte physiology and pathology.

  14. Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth

    PubMed Central

    Hutzler, Marina; Abel, Simone; Alter, Christina; Stockmann, Christian; Kliche, Stefanie; Albert, Juliane; Sparwasser, Tim; Sakaguchi, Shimon; Westendorf, Astrid M.; Schadendorf, Dirk; Buer, Jan; Helfrich, Iris

    2012-01-01

    Infiltration of Foxp3+ regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3+ T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell–specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3+ T reg cells were significantly reduced accompanied by enhanced activation of CD8+ T cells within tumors of T cell–specific Nrp-1–deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1+ T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3+ T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression. PMID:23045606

  15. Osmotic and aging effects in caviar oocytes throughout water and lipid changes assessed by 1H NMR T1 and T2 relaxation and MRI.

    PubMed

    Gussoni, Maristella; Greco, Fulvia; Vezzoli, Alessandra; Paleari, Maria Antonietta; Moretti, Vittorio Maria; Lanza, Barbara; Zetta, Lucia

    2007-01-01

    By combining NMR relaxation spectroscopy and magnetic resonance imaging techniques, unsalted (us) and salted (s) caviar (Acipenser transmontanus) oocytes were characterized over a storage period of up to 90 days. The aging and the salting effects on the two major cell constituents, water and lipids, were separately assessed. T1 and T2 decays were interpreted by assuming a two-site exchange model. At Day 0, two water compartments that were not in fast exchange were identified by the T1 relaxation measurements on the us oocytes. In the s samples, T1 decay was monoexponential. During the time of storage, an increment of the free water amount was found for the us oocytes, ascribed to an increased metabolism. T1 and T2 of the s oocytes shortened as a consequence of the osmotic stress produced by salting. Selective images showed the presence of water endowed with different regional mobility that severely changed during the storage. Lipid T1 relaxation decays collected on us and s samples were found to be biexponential, and the T1 values lengthened during storage. In us and s oocytes, the increased lipid mobility with the storage was ascribed to lipolysis. Selective images of us samples showed lipids that were confined to the cytoplasm for up to 60 days of storage.

  16. Rapid Biodegradation of the Herbicide 2,4-Dichlorophenoxyacetic Acid by Cupriavidus gilardii T-1.

    PubMed

    Wu, Xiangwei; Wang, Wenbo; Liu, Junwei; Pan, Dandan; Tu, Xiaohui; Lv, Pei; Wang, Yi; Cao, Haiqun; Wang, Yawen; Hua, Rimao

    2017-05-10

    Phytotoxicity and environmental pollution of residual herbicides have caused much public concern during the past several decades. An indigenous bacterial strain capable of degrading 2,4-dichlorophenoxyacetic acid (2,4-D), designated T-1, was isolated from soybean field soil and identified as Cupriavidus gilardii. Strain T-1 degraded 2,4-D 3.39 times more rapidly than the model strain Cupriavidus necator JMP134. T-1 could also efficiently degrade 2-methyl-4-chlorophenoxyacetic acid (MCPA), MCPA isooctyl ester, and 2-(2,4-dichlorophenoxy)propionic acid (2,4-DP). Suitable conditions for 2,4-D degradation were pH 7.0-9.0, 37-42 °C, and 4.0 mL of inoculums. Degradation of 2,4-D was concentration-dependent. 2,4-D was degraded to 2,4-dichlorophenol (2,4-DCP) by cleavage of the ether bond and then to 3,5-dichlorocatechol (3,5-DCC) via hydroxylation, followed by ortho-cleavage to cis-2-dichlorodiene lactone (CDL). The metabolites 2,4-DCP or 3,5-DCC at 10 mg L -1 were completely degraded within 16 h. Fast degradation of 2,4-D and its analogues highlights the potential for use of C. gilardii T-1 in bioremediation of phenoxyalkanoic acid herbicides.

  17. Variants within the calpain-10 gene and relationships with type 2 diabetes (T2DM) and T2DM-related traits among Tunisian Arabs.

    PubMed

    Ezzidi, I; Mtiraoui, N; Nemr, R; Kacem, M; Al-Khateeb, G M; Mahjoub, T; Almawi, W Y

    2010-11-01

    Common variations in the calpain 10 (CAPN10) gene variants UCSNP-43, UCSNP-19 and UCSNP-63, and the 112/121 diplotype, are associated with an increased risk of type 2 diabetes (T2DM) and T2DM-related traits. The association of UCSNP-43, -19 and -63 CAPN10 SNPs with T2DM was assessed in 917 Tunisian T2DM patients and 748 ethnically matched non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP. Significant differences in UCSNP-19 MAF, but not UCSNP-43 or -63, and genotype distribution were seen between patients and controls. Heterogeneity in UCSNP-19, but not UCSNP-43 and -63, genotype distribution was noted according to geographical origin. Obesity was associated with UCSNP-19, while raised fasting glucose was associated with UCSNP-63, and increased HDL was associated with UCSNP-43. Enrichment of homozygous UCSNP-19 2/2 was seen in overweight and obese compared with lean patients; logistic-regression analyses demonstrated a positive association of the 2/2 genotype with overweight [P=0.003; OR (95% CI)=2.07 (1.28-3.33)] and obese [P=0.021; OR (95% CI)=1.83 (1.10-3.07)] patients. Of the six CAPN10 haplotypes identified, significant enrichment of only haplotype 111 was seen in T2DM patients [Pc=0.034; OR (95% CI)=1.22 (1.06-1.41)], while the frequency of all identified CAPN10 diplotypes, including the high-risk 112/121, was comparable between patients and controls. While CAPN10 UCSNP-19 SNP and haplotype 111 contribute to the risk of T2DM in Tunisian subjects, no significant association between CAPN10 diplotypes and T2DM was demonstrated. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  18. Breast Lesions: Diagnosis Using Diffusion Weighted Imaging at 1.5T and 3.0T-Systematic Review and Meta-analysis.

    PubMed

    Shi, Ruo-Yang; Yao, Qiu-Ying; Wu, Lian-Ming; Xu, Jian-Rong

    2018-06-01

    We compared the diagnostic performance of diffusion weighted imaging (DWI) acquired with 1.5T and 3.0T magnetic resonance (MR) units in differentiating malignant breast lesions from benign ones. A comprehensive search of the PubMed and Embase databases was performed for studies reported from January 1, 2000 to February 19, 2016. The quality of the included studies was assessed. Statistical analysis included pooling of diagnostic sensitivity and specificity and assessing data inhomogeneity and publication bias. A total of 61 studies were included after a full-text review. These included 4778 patients and 5205 breast lesions. The overall sensitivity and specificity were 90% (95% confidence interval [CI], 88%-92%) and 86% (95% CI, 82%-89%), respectively. The pooled diagnostic odds ratio was 53 (95% CI, 37-74). For breast cancer versus benign lesions, the area under the curve was 0.94 (95% CI, 0.92-0.96). For the 44 studies that used a 1.5T MR unit, the pooled sensitivity and specificity were 91% (95% CI, 89%-92%) and 86% (95% CI, 81%-90%), respectively. For the 17 studies that used a 3.0T MR unit, the pooled sensitivity and specificity were 88% (95% CI, 83%-91%) and 84% (95% CI, 0.78-0.89), respectively. Publication bias and significant heterogeneity were observed; however, no threshold was found among the 61 studies. No significant difference was found in the sensitivity or specificity between the subgroups. The results of the comparison between the subgroups that had used either a 1.5T or 3.0T MR unit suggest that the diagnostic accuracy for breast cancer compared with benign lesions is not significantly different. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. T1- and T2*-dominant extravasation correction in DSC-MRI: Part I—theoretical considerations and implications for assessment of tumor hemodynamic properties

    PubMed Central

    Bjornerud, Atle; Sorensen, A Gregory; Mouridsen, Kim; Emblem, Kyrre E

    2011-01-01

    We present a novel contrast agent (CA) extravasation-correction method based on analysis of the tissue residue function for assessment of multiple hemodynamic parameters. The method enables semiquantitative determination of the transfer constant and can be used to distinguish between T1- and T2*-dominant extravasation effects, while being insensitive to variations in tissue mean transit time (MTT). Results in 101 patients with confirmed glioma suggest that leakage-corrected absolute cerebral blood volume (CBV) values obtained with the proposed method provide improved overall survival prediction compared with normalized CBV values combined with an established leakage-correction method. Using a standard gradient-echo echo-planar imaging sequence, ∼60% and 10% of tumors with detectable CA extravasation mainly exhibited T1- and T2*-dominant leakage effects, respectively. The remaining 30% of leaky tumors had mixed T1- and T2*-dominant effects. Using an MTT-sensitive correction method, our results show that CBV is underestimated when tumor MTT is significantly longer than MTT in the reference tissue. Furthermore, results from our simulations suggest that the relative contribution of T1- versus T2*-dominant extravasation effects is strongly dependent on the effective transverse relaxivity in the extravascular space and may thus be a potential marker for cellular integrity and tissue structure. PMID:21505483

  20. T Regulatory Cell Induced Foxp3 Binds the IL2, IFNγ, and TNFα Promoters in Virus-Specific CD8+ T Cells from Feline Immunodeficiency Virus Infected Cats.

    PubMed

    Wang, Yan; Nag, Mukta; Tuohy, Joanne L; De Paris, Kristina; Fogle, Jonathan E

    2018-03-01

    Polyfunctional CD8 + T cells play a critical role in controlling viremia during AIDS lentiviral infections. However, for most HIV-infected individuals, virus-specific CD8 + T cells exhibit loss of polyfunctionality, including loss of IL2, TNFα, and IFNγ. Using the feline immunodeficiency virus (FIV) model for AIDS lentiviral persistence, our laboratory has demonstrated that FIV-activated Treg cells target CD8 + T cells, leading to a reduction in IL2 and IFNγ production. Furthermore, we have demonstrated that Treg cells induce expression of the repressive transcription factor, Foxp3, in CD8 + T cells. Based upon these findings, we asked if Treg-induced Foxp3 could bind to the IL2, TNFα, and IFNγ promoter regions in virus-specific CD8 + T cells. Following coculture with autologous Treg cells, we demonstrated decreased mRNA levels of IL2 and IFNγ at weeks 4 and 8 postinfection and decreased TNFα at week 4 postinfection in virus-specific CD8 + T cells. We also clearly demonstrated Treg cell-induced Foxp3 expression in virus-specific CD8 + T cells at weeks 1, 4, and 8 postinfection. Finally, we documented Foxp3 binding to the IL2, TNFα, and IFNγ promoters at 8 weeks and 6 months postinfection in virus-specific CD8 + T cells following Treg cell coculture. In summary, the results here clearly demonstrate that Foxp3 inhibits IL2, TNFα, and IFNγ transcription by binding to their promoter regions in lentivirus-specific CD8 + T cells. We believe this is the first description of this process during the course of AIDS lentiviral infection.

  1. Influence of MC3T3-E1 preosteoblast culture on the corrosion of a T6-treated AZ91 alloy

    PubMed Central

    Brooks, Emily K.; Tobias, Menachem E.; Yang, Shuying; Bone, Lawrence B.; Ehrensberger, Mark T.

    2015-01-01

    This study investigated the corrosion of artificially aged T6 heat-treated Mg-9%Al-1%Zn (AZ91) for biomedical applications. Corrosion tests and surface analysis were completed both with and without a monolayer of mouse preosteoblast MC3T3-E1 cells cultured on the sample. Electrochemical impedance spectroscopy (EIS) and inductively coupled plasma mass spectroscopy (ICPMS) were used to explore the corrosion processes after either 3 or 21 days of AZ91 incubation in cell culture medium (CCM). The EIS showed both the inner layer resistance (Rin) and outer layer resistance (Rout) were lower for samples without cells cultured on the surface at 3 days (Rin = 2.64 e4 Ω/cm2, Rout = 140 Ω/cm2) compared to 21 days (Rin = 3.60 e4 Ω/cm2, Rout = 287 Ω/cm2) due to precipitation of magnesium and calcium phosphates over time. Samples with preosteoblasts cultured on the surface had a slower initial corrosion (3 day, Rin = 1.88 e5 Ω/cm2, Rout = 1060 Ω/cm2) which was observed to increase over time (21 day, Rin = 2.99 e4 Ω/cm2, Rout = 287 Ω/cm2). Changes in the corrosion processes were thought to be related to changes in the coverage provided by the cell layer. Our results reveal that the presence of cells and biological processes are able to significantly influence the corrosion rate of AZ91. PMID:25715925

  2. Retracted: Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population.

    PubMed

    Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen

    2015-03-01

    The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with type-2 diabetic nephropathy (T2DN) susceptibility and the risk of type-2 diabetes mellitus (T2DM) developing into T2DN in Caucasian populations is still controversial. A meta-analysis was performed to evaluate the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Sixteen articles were identified for the analysis of the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. Sensitivity analysis according to sample size of case (<100 vs. ≥100) was also performed, and the results were similar to the non-sensitivity analysis. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. However, more studies should be performed in the future. © The Author(s) 2014.

  3. Identification of novel gammadelta T-cell subsets following bacterial infection in the absence of Vgamma1+ T cells: homeostatic control of gammadelta T-cell responses to pathogen infection by Vgamma1+ T cells.

    PubMed

    Newton, Darren J; Andrew, Elizabeth M; Dalton, Jane E; Mears, Rainy; Carding, Simon R

    2006-02-01

    Although gammadelta T cells are a common feature of many pathogen-induced immune responses, the factors that influence, promote, or regulate the response of individual gammadelta T-cell subsets to infection is unknown. Here we show that in the absence of Vgamma1+ T cells, novel subsets of gammadelta T cells, expressing T-cell receptor (TCR)-Vgamma chains that normally define TCRgammadelta+ dendritic epidermal T cells (DETCs) (Vgamma5+), intestinal intraepithelial lymphocytes (iIELs) (Vgamma7+), and lymphocytes associated with the vaginal epithelia (Vgamma6+), are recruited to the spleen in response to bacterial infection in TCR-Vgamma1-/- mice. By comparison of phenotype and structure of TCR-Vgamma chains and/or -Vdelta chains expressed by these novel subsets with those of their epithelium-associated counterparts, the Vgamma6+ T cells elicited in infected Vgamma1-/- mice were shown to be identical to those found in the reproductive tract, from where they are presumably recruited in the absence of Vgamma1+ T cells. By contrast, Vgamma5+ and Vgamma7+ T cells found in infected Vgamma1-/- mice were distinct from Vgamma5+ DETCs and Vgamma7+ iIELs. Functional analyses of the novel gammadelta T-cell subsets identified for infected Vgamma1-/- mice showed that whereas the Vgamma5+ and Vgamma7+ subsets may compensate for the absence of Vgamma1+ T cells by producing similar cytokines, they do not possess cytocidal activity and they cannot replace the macrophage homeostasis function of Vgamma1+ T cells. Collectively, these findings identify novel subsets of gammadelta T cells, the recruitment and activity of which is under the control of Vgamma1+ T cells.

  4. Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells

    PubMed Central

    Ertelt, James M.; Rowe, Jared H.; Mysz, Margaret A.; Singh, Charanjeet; Roychowdhury, Monika; Aguilera, Marijo N.; Way, Sing Sing

    2011-01-01

    T cell activation is controlled by incompletely defined opposing stimulation and suppression signals that together sustain the balance between optimal host defense against infection and peripheral tolerance. Herein, we explored the impacts of Foxp3+ regulatory T cell (Treg) suppression in priming antigen-specific T cell activation under non-infection and infection conditions. We find the transient ablation of Foxp3+ Tregs unleashes the robust expansion and activation of peptide stimulated CD8+ T cells that provide protection against Listeria monocytogenes (Lm) infection in an antigen-specific fashion. By contrast, Treg-ablation had non-significant impacts on the CD8+ T cell response primed by infection with recombinant Lm. Similarly, non-recombinant Lm administered with peptide stimulated the expansion and activation of CD8+ T cells that paralleled the response primed by Treg-ablation. Interestingly, these adjuvant properties of Lm did not require CD8+ T cell stimulation by IL-12 produced in response to infection, but instead were associated with sharp reductions in Foxp3+ Treg suppressive potency. Therefore, Foxp3+ Tregs impose critical barriers that when overcome naturally during infection or artificially with ablation allows the priming of protective antigen-specific CD8+ T cells. PMID:21810602

  5. Thermodynamics of triple helix formation: spectrophotometric studies on the d(A)10.2d(T)10 and d(C+3T4C+3).d(G3A4G3).d(C3T4C3) triple helices.

    PubMed Central

    Pilch, D S; Brousseau, R; Shafer, R H

    1990-01-01

    We have stabilized the d(A)10.2d(T)10 and d(C+LT4C+3).d(G3A4G3).d(C3T4C3) triple helices with either NaCl or MgCl2 at pH 5.5. UV mixing curves demonstrate a 1:2 stoichiometry of purine to pyrimidine strands under the appropriate conditions of pH and ionic strength. Circular dichroic titrations suggest a possible sequence-independent spectral signature for triplex formation. Thermal denaturation profiles indicate the initial loss of the third strand followed by dissociation of the underlying duplex with increasing temperature. Depending on the base sequence and ionic conditions, the binding affinity of the third strand for the duplex at 25 degrees C is two to five orders of magnitude lower than that of the two strands forming the duplex. Thermodynamic parameters for triplex formation were determined for both sequences in the presence of 50 mM MgCl2 and/or 2.0 M NaCl. Hoogsteen base pairs are 0.22-0.64 kcal/mole less stable than Watson-Crick base pairs, depending on ionic conditions and base composition. C+.G and T.A Hoogsteen base pairs appear to have similar stability in the presence of Mg2+ ions at low pH. PMID:2216768

  6. 3D isotropic T2-weighted fast spin echo (VISTA) versus 2D T2-weighted fast spin echo in evaluation of the calcaneofibular ligament in the oblique coronal plane.

    PubMed

    Park, H J; Lee, S Y; Choi, Y J; Hong, H P; Park, S J; Park, J H; Kim, E

    2017-02-01

    To investigate whether the image quality of three-dimensional (3D) volume isotropic fast spin echo acquisition (VISTA) magnetic resonance imaging (MRI) of the calcaneofibular ligament (CFL) view is comparable to that of 2D fast spin echo T2-weighted images (2D T2 FSE) for the evaluation of the CFL, and whether 3D VISTA can replace 2D T2 FSE for the evaluation of CFL injuries. This retrospective study included 76 patients who underwent ankle MRI with CFL views of both 2D T2 FSE MRI and 3D VISTA. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of both techniques were measured. The anatomical identification score and diagnostic performances were evaluated by two readers independently. The diagnostic performances of 3D VISTA and 2D T2 FSE were analysed by sensitivity, specificity, and accuracy for diagnosing CFL injury with reference standards of surgically or clinically confirmed diagnoses. Surgical correlation was performed in 29% of the patients, and clinical examination was used in those who did not have surgery (71%). The SNRs and CNRs of 3D VISTA were significantly higher than those of 2D T2 FSE. The anatomical identification scores on 3D VISTA were inferior to those on 2D T2 FSE, and the differences were statistically significant (p<0.05). There were no significant differences in diagnostic performance between the two sequences when diagnoses were classified as normal or abnormal. Although the image quality of 3D VISTA MRI of the CFL view is not equal to that of 2D T2 FSE for the anatomical evaluation of CFL, 3D VISTA has a diagnostic performance comparable to that of 2D T2 FSE for the diagnosis of CFL injuries. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  7. Phosphoinositide 3–kinase γ participates in T cell receptor–induced T cell activation

    PubMed Central

    Alcázar, Isabela; Marqués, Miriam; Kumar, Amit; Hirsch, Emilio; Wymann, Matthias; Carrera, Ana C.; Barber, Domingo F.

    2007-01-01

    Class I phosphoinositide 3–kinases (PI3Ks) constitute a family of enzymes that generates 3-phosphorylated polyphosphoinositides at the cell membrane after stimulation of protein tyrosine (Tyr) kinase–associated receptors or G protein–coupled receptors (GPCRs). The class I PI3Ks are divided into two types: class IA p85/p110 heterodimers, which are activated by Tyr kinases, and the class IB p110γ isoform, which is activated by GPCR. Although the T cell receptor (TCR) is a protein Tyr kinase–associated receptor, p110γ deletion affects TCR-induced T cell stimulation. We examined whether the TCR activates p110γ, as well as the consequences of interfering with p110γ expression or function for T cell activation. We found that after TCR ligation, p110γ interacts with Gαq/11, lymphocyte-specific Tyr kinase, and ζ-associated protein. TCR stimulation activates p110γ, which affects 3-phosphorylated polyphosphoinositide levels at the immunological synapse. We show that TCR-stimulated p110γ controls RAS-related C3 botulinum substrate 1 activity, F-actin polarization, and the interaction between T cells and antigen-presenting cells, illustrating a crucial role for p110γ in TCR-induced T cell activation. PMID:17998387

  8. Type 1 Responses of Human Vγ9Vδ2 T Cells to Influenza A Viruses▿

    PubMed Central

    Qin, Gang; Liu, Yinping; Zheng, Jian; Ng, Iris H. Y.; Xiang, Zheng; Lam, Kwok-Tai; Mao, Huawei; Li, Hong; Peiris, J. S. Malik; Lau, Yu-Lung; Tu, Wenwei

    2011-01-01

    γδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection. PMID:21752902

  9. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing

    PubMed Central

    Jones, Christopher P.; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-01-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNALys3. Host cell tRNALys is selectively packaged into HIV-1 through a specific interaction between the major tRNALys-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNALys3 is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNALys and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNALys3 in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNALys to increase the efficiency of tRNALys3 annealing to viral RNA. PMID:23264568

  10. T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment

    PubMed Central

    Dong, Lei; Nordlohne, Johannes; Ge, Shuwang; Hertel, Barbara; Melk, Anette; Rong, Song; Haller, Hermann

    2016-01-01

    Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment. PMID:26449606

  11. Curcumin Inhibits CD4+ T Cell Activation, but Augments CD69 Expression and TGF-β1-Mediated Generation of Regulatory T Cells at Late Phase

    PubMed Central

    Kim, Girak; Jang, Mi Seon; Son, Young Min; Seo, Min Ji; Ji, Sang Yun; Han, Seung Hyun; Jung, In Duk; Park, Yeong-Min; Jung, Hyun Jung; Yun, Cheol-Heui

    2013-01-01

    Background Curcumin is a promising candidate for a natural medicinal agent to treat chronic inflammatory diseases. Although CD4+ T cells have been implicated in the pathogenesis of chronic inflammation, whether curcumin directly regulates CD4+ T cells has not been definitively established. Here, we showed curcumin-mediated regulation of CD2/CD3/CD28-initiated CD4+ T cell activation in vitro. Methodology/Principal Findings Primary human CD4+ T cells were stimulated with anti-CD2/CD3/CD28 antibody-coated beads as an in vitro surrogate system for antigen presenting cell-T cell interaction and treated with curcumin. We found that curcumin suppresses CD2/CD3/CD28-initiated CD4+ T cell activation by inhibiting cell proliferation, differentiation and cytokine production. On the other hand, curcumin attenuated the spontaneous decline of CD69 expression and indirectly increased expression of CCR7, L-selectin and Transforming growth factor-β1 (TGF-β1) at the late phase of CD2/CD3/CD28-initiated T cell activation. Curcumin-mediated up-regulation of CD69 at late phase was associated with ERK1/2 signaling. Furthermore, TGF-β1 was involved in curcumin-mediated regulation of T cell activation and late-phase generation of regulatory T cells. Conclusions/Significance Curcumin not merely blocks, but regulates CD2/CD3/CD28-initiated CD4+ T cell activation by augmenting CD69, CCR7, L-selectin and TGF-β1 expression followed by regulatory T cell generation. These results suggest that curcumin could directly reduce T cell-dependent inflammatory stress by modulating CD4+ T cell activation at multiple levels. PMID:23658623

  12. Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

    PubMed

    Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario

    2014-01-01

    The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

  13. Modulation of sweet taste by umami compounds via sweet taste receptor subunit hT1R2.

    PubMed

    Shim, Jaewon; Son, Hee Jin; Kim, Yiseul; Kim, Ki Hwa; Kim, Jung Tae; Moon, Hana; Kim, Min Jung; Misaka, Takumi; Rhyu, Mee-Ra

    2015-01-01

    Although the five basic taste qualities-sweet, sour, bitter, salty and umami-can be recognized by the respective gustatory system, interactions between these taste qualities are often experienced when food is consumed. Specifically, the umami taste has been investigated in terms of whether it enhances or reduces the other taste modalities. These studies, however, are based on individual perception and not on a molecular level. In this study we investigated umami-sweet taste interactions using umami compounds including monosodium glutamate (MSG), 5'-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu) and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3-expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly attenuated by MSG and umami active peptides but not by umami active nucleotides. Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious when sweet receptors are activated by sweeteners that target the extracellular domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate, which interact with the T1R3 transmembrane domain (TMD). Application of umami compounds with lactisole, inhibitory drugs that target T1R3, exerted a more severe inhibitory effect. The inhibition was also observed with F778A sweet receptor mutant, which have the defect in function of T1R3 TMD. These results suggest that umami peptides affect sweet taste receptors and this interaction prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric manner, not to the T1R3. This is the first report to define the interaction between umami and sweet taste receptors.

  14. 3.0T MR imaging of the ankle: Axial traction for morphological cartilage evaluation, quantitative T2 mapping and cartilage diffusion imaging-A preliminary study.

    PubMed

    Jungmann, Pia M; Baum, Thomas; Schaeffeler, Christoph; Sauerschnig, Martin; Brucker, Peter U; Mann, Alexander; Ganter, Carl; Bieri, Oliver; Rummeny, Ernst J; Woertler, Klaus; Bauer, Jan S

    2015-08-01

    To determine the impact of axial traction during high resolution 3.0T MR imaging of the ankle on morphological assessment of articular cartilage and quantitative cartilage imaging parameters. MR images of n=25 asymptomatic ankles were acquired with and without axial traction (6kg). Coronal and sagittal T1-weighted (w) turbo spin echo (TSE) sequences with a driven equilibrium pulse and sagittal fat-saturated intermediate-w (IMfs) TSE sequences were acquired for morphological evaluation on a four-point scale (1=best, 4=worst). For quantitative assessment of cartilage degradation segmentation was performed on 2D multislice-multiecho (MSME) SE T2, steady-state free-precession (SSFP; n=8) T2 and SSFP diffusion-weighted imaging (DWI; n=8) images. Wilcoxon-tests and paired t-tests were used for statistical analysis. With axial traction, joint space width increased significantly and delineation of cartilage surfaces was rated superior (P<0.05). Cartilage surfaces were best visualized on coronal T1-w images (P<0.05). Differences for cartilage matrix evaluation were smaller. Subchondral bone evaluation, motion artifacts and image quality were not significantly different between the acquisition methods (P>0.05). T2 values were lower at the tibia than at the talus (P<0.001). Reproducibility was better for images with axial traction. Axial traction increased the joint space width, allowed for better visualization of cartilage surfaces and improved compartment discrimination and reproducibility of quantitative cartilage parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Topographical Variation of Human Femoral Articular Cartilage Thickness, T1rho and T2 Relaxation Times Is Related to Local Loading during Walking.

    PubMed

    Van Rossom, Sam; Wesseling, Mariska; Van Assche, Dieter; Jonkers, Ilse

    2018-01-01

    Objective Early detection of degenerative changes in the cartilage matrix composition is essential for evaluating early interventions that slow down osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be effective for detecting early changes in proteoglycan and collagen content. To use these magnetic resonance imaging (MRI) methods, it is important to document the topographical variation in cartilage thickness, T1rho and T2 relaxation times in a healthy population. As OA is partially mechanically driven, the relation between these MRI-based parameters and localized mechanical loading during walking was investigated. Design MR images were acquired in 14 healthy adults and cartilage thickness and T1rho and T2 relaxation times were determined. Experimental gait data was collected and processed using musculoskeletal modeling to identify weight-bearing zones and estimate the contact force impulse during gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over the femoral cartilage was analyzed and compared between the weight-bearing and non-weight-bearing zone of the medial and lateral condyle as well as the trochlea. Results Medial condyle cartilage thickness was correlated to the contact force impulse ( r = 0.78). Lower T1rho, indicating increased proteoglycan content, was found in the medial weight-bearing zone. T2 was higher in all weight-bearing zones compared with the non-weight-bearing zones, indicating lower relative collagen content. Conclusions The current results suggest that medial condyle cartilage is adapted as a long-term protective response to localized loading during a frequently performed task and that the weight-bearing zone of the medial condyle has superior weight bearing capacities compared with the non-weight-bearing zones.

  16. Quantitative T2 evaluation at 3.0T compared to morphological grading of the lumbar intervertebral disc: a standardized evaluation approach in patients with low back pain.

    PubMed

    Stelzeneder, David; Welsch, Goetz Hannes; Kovács, Balázs Krisztián; Goed, Sabine; Paternostro-Sluga, Tatjana; Vlychou, Marianna; Friedrich, Klaus; Mamisch, Tallal Charles; Trattnig, Siegfried

    2012-02-01

    The purpose of our investigation was to compare quantitative T2 relaxation time measurement evaluation of lumbar intervertebral discs with morphological grading in young to middle-aged patients with low back pain, using a standardized region-of-interest evaluation approach. Three hundred thirty lumbar discs from 66 patients (mean age, 39 years) with low back pain were examined on a 3.0T MR unit. Sagittal T1-FSE, sagittal, coronal, and axial T2-weighted FSE for morphological MRI, as well as a multi-echo spin-echo sequence for T2 mapping, were performed. Morphologically, all discs were classified according to Pfirrmann et al. Equally sized rectangular regions of interest (ROIs) for the annulus fibrosus were selected anteriorly and posteriorly in the outermost 20% of the disc. The space between was defined as the nucleus pulposus. To assess the reproducibility of this evaluation, inter- and intraobserver statistics were performed. The Pfirrmann scoring of 330 discs showed the following results: grade I: six discs (1.8%); grade II: 189 (57.3%); grade III: 96 (29.1%); grade IV: 38 (11.5%); and grade V: one (0.3%). The mean T2 values (in milliseconds) for the anterior and the posterior annulus, and the nucleus pulposus for the respective Pfirrmann groups were: I: 57/30/239; II: 44/67/129; III: 42/51/82; and IV: 42/44/56. The nucleus pulposus T2 values showed a stepwise decrease from Pfirrmann grade I to IV. The posterior annulus showed the highest T2 values in Pfirrmann group II, while the anterior annulus showed relatively constant T2 values in all Pfirrmann groups. The inter- and intraobserver analysis yielded intraclass correlation coefficients (ICC) for average measures in a range from 0.82 (anterior annulus) to 0.99 (nucleus). Our standardized method of region-specific quantitative T2 relaxation time evaluation seems to be able to characterize different degrees of disc degeneration quantitatively. The reproducibility of our ROI measurements is sufficient to

  17. Relationship Between T1 Slope and Cervical Alignment Following Multilevel Posterior Cervical Fusion Surgery: Impact of T1 Slope Minus Cervical Lordosis.

    PubMed

    Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2016-04-01

    Retrospective study. To assess the relationship between sagittal alignment of the cervical spine and patient-reported health-related quality-of-life scores following multilevel posterior cervical fusion, and to explore whether an analogous relationship exists in the cervical spine using T1 slope minus C2-C7 lordosis (T1S-CL). A recent study demonstrated that, similar to the thoracolumbar spine, the severity of disability increases with sagittal malalignment following cervical reconstruction surgery. From 2007 to 2013, 38 consecutive patients underwent multilevel posterior cervical fusion for cervical stenosis, myelopathy, and deformities. Radiographic measurements included C0-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), T1 slope, and T1S-CL. Pearson correlation coefficients were calculated between pairs of radiographic measures and health-related quality-of-life. C2-C7 SVA positively correlated with neck disability index (NDI) scores (r = 0.495). C2-C7 lordosis (P = 0.001) and T1S-CL (P = 0.002) changes correlated with NDI score changes after surgery. For significant correlations between C2-C7 SVA and NDI scores, regression models predicted a threshold C2-C7 SVA value of 50 mm, beyond which correlations were most significant. The T1S-CL also correlated positively with C2-C7 SVA and NDI scores (r = 0.871 and r = 0.470, respectively). Results of the regression analysis indicated that a C2-C7 SVA value of 50 mm corresponded to a T1S-CL value of 26.1°. This study showed that disability of the neck increased with cervical sagittal malalignment following surgical reconstruction and a greater T1S-CL mismatch was associated with a greater degree of cervical malalignment. Specifically, a mismatch greater than 26.1° corresponded to positive cervical sagittal malalignment, defined as C2-C7 SVA greater than 50 mm. 3.

  18. Calcification of MC3T3-E1 cells on titanium and zirconium.

    PubMed

    Umezawa, Takayuki; Chen, Peng; Tsutsumi, Yusuke; Doi, Hisashi; Ashida, Maki; Suzuki, Shoichi; Moriyama, Keiji; Hanawa, Takao

    2015-01-01

    To confirm similarity of hard tissue compatibility between titanium and zirconium, calcification of MC3T3-E1 cells on titanium and zirconium was evaluated in this study. Mirror-polished titanium (Ti) and zirconium (Zr) disks and zirconium-sputter deposited titanium (Zr/Ti) were employed in this study. The surface of specimens were characterized using scanning electron microscopy and X-ray diffraction. Then, the cellular proliferation, differentiation and calcification of MC3T3-E1 cells on specimens were investigated. The surface of Zr/Ti was much smoother and cleaner than those of Ti and Zr. The proliferation of the cell was the same among three specimens, while the differentiation and calcification on Zr/Ti were faster than those on Ti and Zr. Therefore, Ti and Zr showed the identical hard tissue compatibility according to the evaluation with MC3T3-E1 cells. Sputter deposition may improve cytocompatibility.

  19. Ginsenoside Rb1 promotes browning through regulation of PPARγ in 3T3-L1 adipocytes.

    PubMed

    Mu, Qianqian; Fang, Xin; Li, Xiaoke; Zhao, Dandan; Mo, Fangfang; Jiang, Guangjian; Yu, Na; Zhang, Yi; Guo, Yubo; Fu, Min; Liu, Jun-Li; Zhang, Dongwei; Gao, Sihua

    2015-10-23

    Browning of white adipocyte tissue (WAT) has received considerable attention due to its potential implication in preventing obesity and related comorbidities. Ginsenoside Rb1 is reported to improve glycolipid metabolism and reduce body weight in obese animals. However whether the body reducing effect mediates by browning effect remains unclear. For this purpose, 3T3-L1 adipocytes were used to study the effect of ginsenoside Rb1 on browning adipocytes specific genes and oxygen consumptions. The results demonstrate that 10 μM of ginsenoside Rb1 increases basal glucose uptake and promoted browning evidenced by significant increases in mRNA expressions of UCP-1, PGC-1α and PRDM16 in 3T3-L1 mature adipocytes. Further, ginsenoside Rb1 also increases PPARγ activity. And the browning effect is abrogated by GW9692, a PPARγ antagonist. In addition, ginsenoside Rb1 increases basal respiration rate, ATP production and uncoupling capacity in 3T3-L1 adipocytes. Those effects are also blunted by GW9692. The results suggest that ginsenoside Rb1 promote browning of 3T3-L1 adipocytes through induction of PPARγ. Our finding offer a new source to discover browning agonists and also useful to understand and extend the applications of ginseng and its constituents. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Elevated Cyclic AMP Levels in T Lymphocytes Transformed by Human T-Cell Lymphotropic Virus Type 1

    PubMed Central

    Kress, Andrea K.; Schneider, Grit; Pichler, Klemens; Kalmer, Martina; Fleckenstein, Bernhard; Grassmann, Ralph

    2010-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of adult T-cell leukemia/lymphoma (ATLL), transforms CD4+ T cells to permanent growth through its transactivator Tax. HTLV-1-transformed cells share phenotypic properties with memory and regulatory T cells (T-reg). Murine T-reg-mediated suppression employs elevated cyclic AMP (cAMP) levels as a key regulator. This led us to determine cAMP levels in HTLV-1-transformed cells. We found elevated cAMP concentrations as a consistent feature of all HTLV-1-transformed cell lines, including in vitro-HTLV-1-transformed, Tax-transformed, and patient-derived cells. In transformed cells with conditional Tax expression, high cAMP levels coincided with the presence of Tax but were lost without it. However, transient ectopic expression of Tax alone was not sufficient to induce cAMP. We found specific downregulation of the cAMP-degrading phosphodiesterase 3B (PDE3B) in HTLV-1-transformed cells, which was independent of Tax in transient expression experiments. This is in line with the notion that PDE3B transcripts and cAMP levels are inversely correlated. Overexpression of PDE3B led to a decrease of cAMP in HTLV-1-transformed cells. Decreased expression of PDE3B was associated with inhibitory histone modifications at the PDE3B promoter and the PDE3B locus. In summary, Tax transformation and its continuous expression contribute to elevated cAMP levels, which may be regulated through PDE3B suppression. This shows that HTLV-1-transformed cells assume biological features of long-lived T-cell populations that potentially contribute to viral persistence. PMID:20573814

  1. Atmospheric Dispersion Capability for T2VOC

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oldenburg, Curtis M.

    2005-09-19

    Atmospheric transport by variable-K theory dispersion has been added to T2VOC. The new code, T2VOCA, models flow and transport in the subsurface identically to T2VOC, but includes also the capability for modeling passive multicomponent variable-K theory dispersion in an atmospheric region assumed to be flat, horizontal, and with a logarithmic wind profile. The specification of the logarithmic wind profile in the T2VOC input file is automated through the use of a build code called ATMDISPV. The new capability is demonstrated on 2-D and 3-D example problems described in this report.

  2. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing.

    PubMed

    Jones, Christopher P; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-02-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.

  3. Preparation and physical properties of polycrystalline (Bi1-xPbx)2Sr2Ca2Cu3Oy high T c superconductors

    NASA Astrophysics Data System (ADS)

    Awan, M. S.; Maqsood, M.; Mirza, S. A.; Yousaf, M.; Maqsood, A.

    1995-02-01

    (Bi1-xPbx:)2Sr2Ca2Cu3Oy ( x = 0.3) high critical transition temperature ( T c) superconductors are synthesized by the solid-state reaction method in polycrystalline form. X-ray diffraction (XRD) studies, direct current (dc) electrical resistivity measurements, scanning electron microscopic (SEM) studies, critical current density measurements, and zero-field alternating current (ac) susceptibility measurements are performed to investigate the physical changes, structural changes, and magnetic behavior of the superconducting samples. X-ray diffraction studies show that a high T c phase exists with orthorhombic symmetry in the specimen. According to the XRD data, the lattice parameters of the high T c phase were determined as a = 0.537(1) nm, b = 0.539(1) nm, and c = 3.70(1) nm. The compound exhibits a superconducting transition at 106 ±1 K for zero resistance. The ac susceptibility measurements in zero field confirm the dc electrical resistivity results; hence both support the XRD results. The particle size and structural changes as a function of the cold-pressing and aging effect are also reported.

  4. A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata.

    PubMed

    Oda, Satoko; Funato, Hiromasa; Sato, Fumi; Adachi-Akahane, Satomi; Ito, Masanori; Takase, Kenkichi; Kuroda, Masaru

    2014-06-15

    Vesicular glutamate transporter isoforms, VGluT1-VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus. Thus, it has been strongly suggested that a subset of thalamocortical projections to RSC possesses both VGluT1 and VGluT2. In this study, double-labeled neuronal somata showing both VGluT1 and VGluT2 immunolabelings were found exclusively in the ventral region of AD (vAD). Many double-labeled axon terminals were also found in two major targets of vAD, the rostral part of the reticular thalamic nucleus and layers Ia and III-IV of the retrosplenial granular b cortex (RSGb). Some were also found in layer Ia of the retrosplenial granular a cortex (RSGa). These axon terminals contain significant amounts of both VGluTs. Because the subset of thalamocortical projections to RSC has a unique molecular basis in the glutamatergic transmission system, it might play an important role in the higher cognitive functions processed in the RSC. Furthermore, double-labeled axon terminals of a different type were distributed in RSGb and RSGa. Because they are small and the immunoreactivity of VGluT2 is significantly weaker than that of VGluT1, they seemed to be a subset of corticocortical terminals. Copyright © 2013 Wiley Periodicals, Inc.

  5. Evaluation of shoulder pathology: three-dimensional enhanced T1 high-resolution isotropic volume excitation MR vs two-dimensional fast spin echo T2 fat saturation MR.

    PubMed

    Park, H J; Lee, S Y; Kim, M S; Choi, S H; Chung, E C; Kook, S H; Kim, E

    2015-03-01

    To evaluate the diagnostic accuracy of three-dimensional (3D) enhanced T1 high-resolution isotropic volume excitation (eTHRIVE) shoulder MR for the detection of rotator cuff tears, labral lesions and calcific tendonitis of the rotator cuff in comparison with two-dimensional (2D) fast spin echo T2 fat saturation (FS) MR. This retrospective study included 73 patients who underwent shoulder MRI using the eTHRIVE technique. Shoulder MR images were interpreted separately by two radiologists. They evaluated anatomic identification and image quality of the shoulder joint on routine MRI sequences (axial and oblique coronal T2 FS images) and compared them with the reformatted eTHRIVE images. The images were scored on a four-point scale (0, poor; 1, questionable; 2, adequate; 3, excellent) according to the degree of homogeneous and sufficient fat saturation to penetrate bone and soft tissue, visualization of the glenoid labrum and distinction of the supraspinatus tendon (SST). The diagnostic accuracy of eTHRIVE images compared with routine MRI sequences was evaluated in the setting of rotator cuff tears, glenoid labral injuries and calcific tendonitis of the SST. Fat saturation scores for eTHRIVE were significantly higher than those of the T2 FS for both radiologists. The sensitivity and accuracy of the T2 FS in diagnosing rotor cuff tears were >90%, whereas sensitivity and accuracy of the eTHRIVE method were significantly lower. The sensitivity, specificity and accuracy of both images in diagnosing labral injuries and calcific tendonitis were similar and showed no significant differences. The specificity of both images for the diagnosis of labral injuries and calcific tendonitis was higher than the sensitivities. The accuracy of 3D eTHRIVE imaging was comparable to that of 2D FSE T2 FS for the diagnosis of glenoid labral injury and calcific tendonitis of SST. The 3D eTHRIVE technique was superior to 2D FSE T2 FS in terms of fat saturation. Overall, 3D eTHRIVE was inferior

  6. 26 CFR 1.382-1T - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false [Reserved] 1.382-1T Section 1.382-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-1T [Reserved] ...

  7. 26 CFR 1.181-0T - Table of contents (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Table of contents (temporary). 1.181-0T Section...-0T Table of contents (temporary). This section lists the table of contents for §§ 1.181-1T through 1... deduction allowed. § 1.181-2TElection (temporary). (a) Time and manner of making election. (b) Election by...

  8. The Efficiency of Delone Coverings of the Canonical Tilings T}(*(A_4)) -> T^*(A4) and T}(*(D_6)) -> T^*(D6)

    NASA Astrophysics Data System (ADS)

    Papadopolos, Zorka; Kasner, Gerald

    This chapter is devoted to the coverings of the two quasiperiodic canonical tilings T}(*(A_4)) -> T^*(A4) and T}(*(D_6)) equiv {cal T}(*(2F)) -> T^*(D6) T^*(2F), obtained by projection from the root lattices A4 and D6, respectively. In the first major part of this chapter, in Sect. 5.2, we shall introduce a Delone covering T}(*(A_4)}) -> C^sT^*(A4) of the 2-dimensional decagonal tiling T}(*(A_4)) -> T^*(A4). In the second major part of this chapter, Sect. 5.3, we summarize the results related to the Delone covering of the icosahedral tiling T}(*(D_6)) -> T^*(D6), T}(*(D_6)}) -> CT^*(D6) and determine the zero-, single-, and double- deckings and the resulting thickness of the covering. In the conclusions section, we give some suggestions as to how the definition of the Delone covering might be changed in order to reach some real (full) covering of the icosahedral tiling T}(*(D_6)) -> T^*(D6). In Section 5.2 the definition of the Delone covering is also changed in order to avoid an unnecessary large thickness of the covering.

  9. Growth hormone facilitates 5'-azacytidine-induced myogenic but inhibits 5'-azacytidine-induced adipogenic commitment in C3H10T1/2 mesenchymal stem cells.

    PubMed

    Jia, Dan; Zheng, Weijiang; Jiang, Honglin

    2018-06-01

    The C3H10T1/2 cells are considered mesenchymal stem cells (MSCs) because they can be induced to become the progenitor cells for myocytes, adipocytes, osteoblasts, and chondrocytes by the DNA methyltransferase inhibitor 5'-azacytidine. In this study, we determined the effect of growth hormone (GH) on the myogenic and adipogenic lineage commitment in C3H10T1/2 cells. The C3H10T1/2 cells were treated with recombinant bovine GH in the presence or absence of 5'-azacytidine for 4 days. The myogenic commitment in C3H10T1/2 cells was assessed by immunostaining them for MyoD, the marker for myoblasts, and by determining their capacity to differentiate into the multinucleated myotubes. The adipogenic commitment in C3H10T1/2 cells was assessed by determining their ability to differentiate into adipocytes. Myotubes and adipocyteswere identified by immunocytochemistry and Oil Red O staining, respectively. C3H10T1/2 cells treated with 5'-azacytidine and GH for 4 days contained a greater percentage of MyoD-positive cells than those treated with 5'-axacytidine alone (P < 0.05). The former generated more myotubes than the latter upon induced myoblast differentiation (P < 0.05). However, C3H10T1/2 cells treated with GH alone did not form any myotubes. C3H10T1/2 cells treated with 5'-azacytidine formed adipocytes upon adipocyte differentiation induction, whereas C3H10T1/2 cells treated with GH alone did not form any adipocytes. C3H10T1/2 cells treated with both 5'-azacytidine and GH formed fewer adipocytes than those treated with 5'-azacytidine alone (P < 0.05). Both GHR and IGF-I mRNA expression in C3H10T1/2 cells were increased by 5'-azacytidine (P < 0.05), but neither was affected by GH. Overall, this study showed that GH enhanced 5'-azacytidine-induced commitment in C3H10T1/2 cells to myoblasts but inhibited 5'-azacytidine-induced commitment to preadipocytes. These results support the possibility that GH stimulates skeletal muscle growth and inhibits adipose

  10. Influence of MC3T3-E1 preosteoblast culture on the corrosion of a T6-treated AZ91 alloy.

    PubMed

    Brooks, Emily K; Tobias, Menachem E; Yang, Shuying; Bone, Lawrence B; Ehrensberger, Mark T

    2016-02-01

    This study investigated the corrosion of artificially aged T6 heat-treated Mg-9%Al-1%Zn (AZ91) for biomedical applications. Corrosion tests and surface analysis were completed both with and without a monolayer of mouse preosteoblast MC3T3-E1 cells cultured on the sample. Electrochemical impedance spectroscopy (EIS) and inductively coupled plasma mass spectroscopy (ICPMS) were used to explore the corrosion processes after either 3 or 21 days of AZ91 incubation in cell culture medium (CCM). The EIS showed both the inner layer resistance (Rin ) and outer layer resistance (Rout ) were lower for samples without cells cultured on the surface at 3 days (Rin  = 2.64 e4 Ω/cm(2) , Rout  = 140 Ω/cm(2) ) compared to 21 days (Rin  = 3.60 e4 Ω/cm(2) , Rout  = 287 Ω/cm(2) ) due to precipitation of magnesium and calcium phosphates over time. Samples with preosteoblasts cultured on the surface had a slower initial corrosion (3 day, Rin  = 1.88 e5 Ω/cm(2) , Rout  = 1060 Ω/cm(2) ) which was observed to increase over time (21 day, Rin  = 2.99 e4 Ω/cm(2) , Rout  = 287 Ω/cm(2) ). Changes in the corrosion processes were thought to be related to changes in the coverage provided by the cell layer. Our results reveal that the presence of cells and biological processes are able to significantly influence the corrosion rate of AZ91. © 2015 Wiley Periodicals, Inc.

  11. Statistical power comparisons at 3T and 7T with a GO / NOGO task.

    PubMed

    Torrisi, Salvatore; Chen, Gang; Glen, Daniel; Bandettini, Peter A; Baker, Chris I; Reynolds, Richard; Yen-Ting Liu, Jeffrey; Leshin, Joseph; Balderston, Nicholas; Grillon, Christian; Ernst, Monique

    2018-07-15

    The field of cognitive neuroscience is weighing evidence about whether to move from standard field strength to ultra-high field (UHF). The present study contributes to the evidence by comparing a cognitive neuroscience paradigm at 3 Tesla (3T) and 7 Tesla (7T). The goal was to test and demonstrate the practical effects of field strength on a standard GO/NOGO task using accessible preprocessing and analysis tools. Two independent matched healthy samples (N = 31 each) were analyzed at 3T and 7T. Results show gains at 7T in statistical strength, the detection of smaller effects and group-level power. With an increased availability of UHF scanners, these gains may be exploited by cognitive neuroscientists and other neuroimaging researchers to develop more efficient or comprehensive experimental designs and, given the same sample size, achieve greater statistical power at 7T. Published by Elsevier Inc.

  12. Towards clinical assessment of velopharyngeal closure using MRI: evaluation of real-time MRI sequences at 1.5 and 3 T.

    PubMed

    Scott, A D; Boubertakh, R; Birch, M J; Miquel, M E

    2012-11-01

    The objective of this study was to demonstrate soft palate MRI at 1.5 and 3 T with high temporal resolution on clinical scanners. Six volunteers were imaged while speaking, using both four real-time steady-state free-precession (SSFP) sequences at 3 T and four balanced SSFP (bSSFP) at 1.5 T. Temporal resolution was 9-20 frames s(-1) (fps), spatial resolution 1.6 × 1.6 × 10.0-2.7 × 2.7 × 10.0 mm(3). Simultaneous audio was recorded. Signal-to-noise ratio (SNR), palate thickness and image quality score (1-4, non-diagnostic-excellent) were evaluated. SNR was higher at 3 T than 1.5 T in the relaxed palate (nasal breathing position) and reduced in the elevated palate at 3 T, but not 1.5 T. Image quality was not significantly different between field strengths or sequences (p=NS). At 3 T, 40% acquisitions scored 2 and 56% scored 3. Most 1.5 T acquisitions scored 1 (19%) or 4 (46%). Image quality was more dependent on subject or field than sequence. SNR in static images was highest with 1.9 × 1.9 × 10.0 mm(3) resolution (10 fps) and measured palate thickness was similar (p=NS) to that at the highest resolution (1.6 × 1.6 × 10.0 mm(3)). SNR in intensity-time plots through the soft palate was highest with 2.7 × 2.7 × 10.0 mm(3) resolution (20 fps). At 3 T, SSFP images are of a reliable quality, but 1.5 T bSSFP images are often better. For geometric measurements, temporal should be traded for spatial resolution (1.9 × 1.9 × 10.0 mm(3), 10 fps). For assessment of motion, temporal should be prioritised over spatial resolution (2.7 × 2.7 × 10.0 mm(3), 20 fps). Advances in knowledge Diagnostic quality real-time soft palate MRI is possible using clinical scanners and optimised protocols have been developed. 3 T SSFP imaging is reliable, but 1.5 T bSSFP often produces better images.

  13. Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development.

    PubMed

    Wang, Haopeng; Holst, Jeff; Woo, Seng-Ryong; Guy, Cliff; Bettini, Matt; Wang, Yao; Shafer, Aaron; Naramura, Mayumi; Mingueneau, Michaël; Dragone, Leonard L; Hayes, Sandra M; Malissen, Bernard; Band, Hamid; Vignali, Dario A A

    2010-04-07

    Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T-cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is mediated by the CD3varepsilon proline-rich sequence, Lck, c-Cbl, and SLAP, which collectively trigger the dynamin-dependent downmodulation, lysosomal sequestration and degradation of surface TCR:CD3 complexes. Blocking this tonic ubiquitylation by mutating all the lysines in the CD3 cytoplasmic tails significantly upregulates TCR levels on DP thymocytes. Mimicking monoubiquitylation by expression of a CD3zeta-monoubiquitin (monoUb) fusion molecule significantly reduces TCR levels on immature thymocytes. Moreover, modulating CD3 ubiquitylation alters immunological synapse (IS) formation and Erk phosphorylation, thereby shifting the signalling threshold for positive and negative selection, and regulatory T-cell development. Thus, tonic TCR:CD3 ubiquitylation results in precise regulation of TCR expression on immature T cells, which is required to maintain the fidelity of T-cell development.

  14. Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development

    PubMed Central

    Wang, Haopeng; Holst, Jeff; Woo, Seng-Ryong; Guy, Cliff; Bettini, Matt; Wang, Yao; Shafer, Aaron; Naramura, Mayumi; Mingueneau, Michaël; Dragone, Leonard L; Hayes, Sandra M; Malissen, Bernard; Band, Hamid; Vignali, Dario A A

    2010-01-01

    Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T-cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is mediated by the CD3ɛ proline-rich sequence, Lck, c-Cbl, and SLAP, which collectively trigger the dynamin-dependent downmodulation, lysosomal sequestration and degradation of surface TCR:CD3 complexes. Blocking this tonic ubiquitylation by mutating all the lysines in the CD3 cytoplasmic tails significantly upregulates TCR levels on DP thymocytes. Mimicking monoubiquitylation by expression of a CD3ζ-monoubiquitin (monoUb) fusion molecule significantly reduces TCR levels on immature thymocytes. Moreover, modulating CD3 ubiquitylation alters immunological synapse (IS) formation and Erk phosphorylation, thereby shifting the signalling threshold for positive and negative selection, and regulatory T-cell development. Thus, tonic TCR:CD3 ubiquitylation results in precise regulation of TCR expression on immature T cells, which is required to maintain the fidelity of T-cell development. PMID:20150895

  15. RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hahm, Jong Ryeal; Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27; Ahmed, Mahmoud

    3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-L-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 wasmore » highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-L-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity. - Highlights: • Overexpression of GFP-LC3 in 3T3-L1 cells produces intracellular lipid droplets. • SREBP2 is highly activated in preadipocytes transfected with adenoviral GFP-LC3. • RKIP phosphorylation at serine 153 is significantly increased during adipogenesis. • RKIP knockdown promotes ERK1 and PPARγ activation during adipogenesis. • RKIP-dependent ERK1 activation increases

  16. Comparison of axial T1 spin-echo and T1 fat-saturation magnetic resonance imaging techniques in the diagnosis of chondromalacia patellae.

    PubMed

    Vanarthos, W J; Pope, T L; Monu, J U

    1994-12-01

    To test the diagnostic value of T1 spin-echo and T1 fat-saturated magnetic resonance images (MRIs), we reviewed axial T1-weighted images with and without fat saturation in 20 patients with clinically suspected chondromalacia of the patella. All scans were obtained on 1.5-MR units. The scans were randomly ordered and reviewed independently at different times by two radiologists without knowledge of the arthroscopy results. The sensitivity of the individual techniques for detecting grade 3 or 4 chondromalacia patellae was 92% for fat-saturated axial T1-weighted images alone, and 67% for axial T1-weighted images without fat saturation. The sensitivity of the combined techniques was 100% for grades 3 and 4 and 90% for all grades (0 to 4). Chondromalacia patellae is diagnosed more accurately by using T1 fat saturation than by using T1 spin-echo images. With a combination of the two techniques, accuracy is 90% to 100%.

  17. Expression of Master Regulators of T-cell, Helper T-cell and Follicular Helper T-cell Differentiation in Angioimmunoblastic T-cell Lymphoma.

    PubMed

    Matsumoto, Yosuke; Nagoshi, Hisao; Yoshida, Mihoko; Kato, Seiichi; Kuroda, Junya; Shimura, Kazuho; Kaneko, Hiroto; Horiike, Shigeo; Nakamura, Shigeo; Taniwaki, Masafumi

    2017-11-01

    Objective It has been postulated that the normal counterpart of angioimmunoblastic T-cell lymphoma (AITL) is the follicular helper T-cell (TFH). Recent immunological studies have identified several transcription factors responsible for T-cell differentiation. The master regulators associated with T-cell, helper T-cell (Th), and TFH differentiation are reportedly BCL11B, Th-POK, and BCL6, respectively. We explored the postulated normal counterpart of AITL with respect to the expression of the master regulators of T-cell differentiation. Methods We performed an immunohistochemical analysis in 15 AITL patients to determine the expression of the master regulators and several surface markers associated with T-cell differentiation. Results BCL11B was detected in 10 patients (67%), and the surface marker of T-cells (CD3) was detected in all patients. Only 2 patients (13%) expressed the marker of naïve T-cells (CD45RA), but all patients expressed the marker of effector T-cells (CD45RO). Nine patients expressed Th-POK (60%), and 7 (47%) expressed a set of surface antigens of Th (CD4-positive and CD8-negative). In addition, BCL6 and the surface markers of TFH (CXCL13, PD-1, and SAP) were detected in 11 (73%), 8 (53%), 14 (93%), and all patients, respectively. Th-POK-positive/BCL6-negative patients showed a significantly shorter overall survival (OS) than the other patients (median OS: 33.0 months vs. 74.0 months, p=0.020; log-rank test). Conclusion Many of the AITL patients analyzed in this study expressed the master regulators of T-cell differentiation. The clarification of the diagnostic significance and pathophysiology based on the expression of these master regulators in AITL is expected in the future.

  18. Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human Vγ22 T Cells

    PubMed Central

    Wang, Hong; Morita, Craig T.

    2016-01-01

    22 T cells play important roles in human immunity to pathogens and in cancer immunotherapy by responding to isoprenoid metabolites, such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and isopentenyl pyrophosphate. The Ig superfamily protein butyrophilin (BTN)3A1 was shown to be required for prenyl pyrophosphate stimulation. We proposed that the intracellular B30.2 domain of BTN3A1 binds prenyl pyrophosphates, resulting in a change in the extracellular BTN3A1 dimer that is detected by Vγ22 TCRs. Such B30.2 binding was demonstrated recently. However, other investigators reported that the extracellular BTN3A1 IgV domain binds prenyl pyrophosphates, leading to the proposal that the Vγ22 TCR recognizes the complex. To distinguish between these mechanisms, we mutagenized residues in the two binding sites and tested the mutant BTN3A1 proteins for their ability to mediate prenyl pyrophosphate stimulation of Vγ22 T cells to proliferate and secrete TNF-α. Mutagenesis of residues in the IgV site had no effect on Vγ22 T cell proliferation or secretion of TNF-α. In contrast, mutagenesis of residues within the basic pocket and surrounding V regions of the B30.2 domain abrogated prenyl pyrophosphate-induced proliferation. Mutations of residues making hydrogen bonds to the pyrophosphate moiety also abrogated TNF-α secretion, as did mutation of aromatic residues making contact with the alkenyl chain. Some mutations further from the B30.2 binding site also diminished stimulation, suggesting that the B30.2 domain may interact with a second protein. These findings support intracellular sensing of prenyl pyrophosphates by BTN3A1 rather than extracellular presentation. PMID:26475929

  19. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kusunoki, Chisato, E-mail: yosizaki@belle.shiga-med.ac.jp; Yang, Liu; Yoshizaki, Takeshi

    Highlights: Black-Right-Pointing-Pointer Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. Black-Right-Pointing-Pointer EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. Black-Right-Pointing-Pointer Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid ({omega}3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of {omega}3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treatedmore » with {omega}3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). {omega}3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with {omega}3-PUFA prevented H{sub 2}O{sub 2}-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.« less

  20. Chaperonin-containing T-complex Protein 1 Subunit ζ Serves as an Autoantigen Recognized by Human Vδ2 γδ T Cells in Autoimmune Diseases.

    PubMed

    Chen, Hui; You, Hongqin; Wang, Lifang; Zhang, Xuan; Zhang, Jianmin; He, Wei

    2016-09-16

    Human γδ T cells recognize conserved endogenous and stress-induced antigens typically associated with autoimmune diseases. However, the role of γδ T cells in autoimmune diseases is not clear. Few autoimmune disease-related antigens recognized by T cell receptor (TCR) γδ have been defined. In this study, we compared Vδ2 TCR complementarity-determining region 3 (CDR3) between systemic lupus erythematosus (SLE) patients and healthy donors. Results show that CDR3 length distribution differed significantly and displayed oligoclonal characteristics in SLE patients when compared with healthy donors. We found no difference in the frequency of Jδ gene fragment usage between these two groups. According to the dominant CDR3δ sequences in SLE patients, synthesized SL2 peptides specifically bound to human renal proximal tubular epithelial cell line HK-2; SL2-Vm, a mutant V sequence of SL2, did not bind. We identified the putative protein ligand chaperonin-containing T-complex protein 1 subunit ζ (CCT6A) using SL2 as a probe in HK-2 cell protein extracts by affinity chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. We found CCT6A expression on the surface of HK-2 cells. Cytotoxicity of only Vδ2 γδ T cells to HK-2 cells was blocked by anti-CCT6A antibody. Finally, we note that CCT6A concentration was significantly increased in plasma of SLE and rheumatoid arthritis patients. These data suggest that CCT6A is a novel autoantigen recognized by Vδ2 γδ T cells, which deepens our understanding of mechanisms in autoimmune diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of the knee.

    PubMed

    Van Dyck, Pieter; Kenis, Christoph; Vanhoenacker, Filip M; Lambrecht, Valérie; Wouters, Kristien; Gielen, Jan L; Dossche, Lieven; Parizel, Paul M

    2014-06-01

    The aim of this prospective study was to compare routine MRI scans of the knee at 1.5 and 3 T obtained in the same individuals in terms of their performance in the diagnosis of cartilage lesions. One hundred patients underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR examinations consisted of multiplanar 2D turbo spin-echo sequences. Three radiologists independently graded all articular surfaces of the knee joint seen at MRI. With arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the proportion of correctly graded cartilage lesions within the knee joint were determined and compared using resampling statistics. For all readers and surfaces combined, the respective sensitivity, specificity, and accuracy for detecting all grades of cartilage lesions in the knee joint using MRI were 60, 96, and 87% at 1.5 T and 69, 96, and 90% at 3 T. There was a statistically significant improvement in sensitivity (p < 0.05), but not specificity or accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a statistically significant (p < 0.05) improvement in the proportion of correctly graded cartilage lesions at 3 T as compared to 1.5 T. A 3-T MR protocol significantly improves diagnostic performance for the purpose of detecting cartilage lesions within the knee joint, when compared with a similar protocol performed at 1.5 T. III.

  2. Comparison of biochemical cartilage imaging techniques at 3 T MRI.

    PubMed

    Rehnitz, C; Kupfer, J; Streich, N A; Burkholder, I; Schmitt, B; Lauer, L; Kauczor, H-U; Weber, M-A

    2014-10-01

    To prospectively compare chemical-exchange saturation-transfer (CEST) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping to assess the biochemical cartilage properties of the knee. Sixty-nine subjects were prospectively included (median age, 42 years; male/female = 32/37) in three cohorts: 10 healthy volunteers, 40 patients with clinically suspected cartilage lesions, and 19 patients about 1 year after microfracture therapy. T2 mapping, dGEMRIC, and CEST were performed at a 3 T MRI unit using a 15-channel knee coil. Parameter maps were evaluated using region-of-interest analysis of healthy cartilage, areas of chondromalacia and repair tissue. Differentiation of damaged from healthy cartilage was assessed using receiver-operating characteristic (ROC) analysis. Chondromalacia grade 2-3 had significantly higher CEST values (P = 0.001), lower dGEMRIC (T1-) values (P < 0.001) and higher T2 values (P < 0.001) when compared to the normal appearing cartilage. dGEMRIC and T2 mapping correlated moderately negative (Spearman coefficient r = -0.56, P = 0.0018) and T2 mapping and CEST moderately positive (r = 0.5, P = 0.007), while dGEMRIC and CEST did not significantly correlate (r = -0.311, P = 0.07). The repair tissue revealed lower dGEMRIC values (P < 0.001) and higher CEST values (P < 0.001) with a significant negative correlation (r = -0.589, P = 0.01), whereas T2 values were not different (P = 0.54). In healthy volunteers' cartilage, CEST and dGEMRIC showed moderate positive correlation (r = 0.56), however not reaching significance (P = 0.09). ROC-analysis demonstrated non-significant differences of T2 mapping vs CEST (P = 0.14), CEST vs dGEMRIC (P = 0.89), and T2 mapping vs dGEMRIC (P = 0.12). CEST is able to detect normal and damaged cartilage and is non-inferior in distinguishing both when compared to dGEMRIC and T2 mapping. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. Effects of Age, Gender and Hemispheric Location on T2 Hypointensity in the Pulvinar at 3T.

    PubMed

    White, Matthew L; Zhang, Yan; Helvey, Jason T; Yu, Fang; Omojola, Matthew F

    2014-12-01

    Pulvinar signal intensity decrease on T2-weighted images has been reported in some neurological abnormalities. We aimed to define the normal T2 signal hypointensity pattern present in the pulvinar to avoid erroneous radiological interpretation. One hundred and forty-two subjects (54 men and 88 women; age range 9-91 years) with unremarkable brain 3T MR findings were enrolled. MR images were analyzed with regard to signal intensity of the pulvinar relative to the thalamus on fluid attenuated inversion recovery images. Effects of age, gender and hemispheric location on the degree of T2 hypointensity were statistically analyzed. The statistical association was measured between the pattern of signal changes in the pulvinar region and that in the putamen and the globus pallidus. We detected a linear signal decrease in the pulvinar region with age. The male subjects had a more rapid decrease of signal with age than female subjects. The right pulvinar region had a higher chance of hypointensity compared to the left. A positive linear association was found when signal change from the pulvinar region was compared with signal in the putamen and globus pallidus. We detected a linear signal decrease with age in the pulvinar. The physiological signal features of the pulvinar also depend on gender and hemispheric lateralization. The pattern of signal change in the pulvinar is similar to but not the same as that in the putamen and globus pallidus.

  4. 3,3′-Diindolylmethane Induces G1 Arrest and Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia Cells

    PubMed Central

    Shorey, Lyndsey E.; Hagman, Amanda M.; Williams, David E.; Ho, Emily; Dashwood, Roderick H.; Benninghoff, Abby D.

    2012-01-01

    Certain bioactive food components, including indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) from cruciferous vegetables, have been shown to target cellular pathways regulating carcinogenesis. Previously, our laboratory showed that dietary I3C is an effective transplacental chemopreventive agent in a dibenzo[def,p]chrysene (DBC)-dependent model of murine T-cell lymphoblastic lymphoma. The primary objective of the present study was to extend our chemoprevention studies in mice to an analogous human neoplasm in cell culture. Therefore, we tested the hypothesis that I3C or DIM may be chemotherapeutic in human T-cell acute lymphoblastic leukemia (T-ALL) cells. Treatment of the T-ALL cell lines CCRF-CEM, CCRF-HSB2, SUP-T1 and Jurkat with DIM in vitro significantly reduced cell proliferation and viability at concentrations 8- to 25-fold lower than the parent compound I3C. DIM (7.5 µM) arrested CEM and HSB2 cells at the G1 phase of the cell cycle and 15 µM DIM significantly increased the percentage of apoptotic cells in all T-ALL lines. In CEM cells, DIM reduced protein expression of cyclin dependent kinases 4 and 6 (CDK4, CDK6) and D-type cyclin 3 (CCND3); DIM also significantly altered expression of eight transcripts related to human apoptosis (BCL2L10, CD40LG, HRK, TNF, TNFRSF1A, TNFRSF25, TNFSF8, TRAF4). Similar anticancer effects of DIM were observed in vivo. Dietary exposure to 100 ppm DIM significantly decreased the rate of growth of human CEM xenografts in immunodeficient SCID mice, reduced final tumor size by 44% and increased the apoptotic index compared to control-fed mice. Taken together, our results demonstrate a potential for therapeutic application of DIM in T-ALL. PMID:22514694

  5. Incidental pineal cysts in children who undergo 3-T MRI.

    PubMed

    Whitehead, Matthew T; Oh, Christopher C; Choudhri, Asim F

    2013-12-01

    Pineal cysts, both simple and complex, are commonly encountered in children. More cysts are being detected with MR technology; however, nearly all pineal cysts are benign and require no follow-up. To discover the prevalence of pineal cysts in children at our institution who have undergone high-resolution 3-T MRI. We retrospectively reviewed 100 consecutive 3-T brain MRIs in children ages 1 month to 17 years (mean 6.8 ± 5.1 years). We evaluated 3-D volumetric T1-W imaging, axial T2-W imaging, axial T2-W FLAIR (fluid attenuated inversion recovery) and coronal STIR (short tau inversion recovery) sequences. Pineal parenchymal and cyst volumes were measured in three planes. Cysts were analyzed for the presence and degree of complexity. Pineal cysts were present in 57% of children, with a mean maximum linear dimension of 4.2 mm (range 1.5-16 mm). Of these cysts, 24.6% showed thin septations or fluid levels reflecting complexity. None of the cysts demonstrated complete T2/FLAIR signal suppression. No cyst wall thickening or nodularity was present. There was no significant difference between the ages of children with and without cysts. Cysts were more commonly encountered in girls than boys (67% vs. 52%; P = 0.043). There was a slight trend toward increasing pineal gland volume with age. Pineal cysts are often present in children and can be incidentally detected by 3-T MRI. Characteristic-appearing pineal cysts in children are benign, incidental findings, for which follow-up is not required if there are no referable symptoms or excessive size.

  6. Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells1

    PubMed Central

    Joshi, Nikhil S.; Cui, Weiguo; Dominguez, Claudia; Chen, Jonathan H.; Hand, Timothy W.; Kaech, Susan M.

    2011-01-01

    Memory CD8 T cells acquire TEM properties following reinfection, and may reach terminally differentiated, senescent states (“Hayflick limit”) after multiple infections. The signals controlling this process are not well understood, but we found that the degree of 2o effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and pre-existing memory CD8 T cell number (i.e., 1o memory CD8 T cell precursor frequency) present during secondary infection. Compared to naïve cells, memory CD8 T cells were predisposed towards terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of antigen. TE cell formation following 2o or 3o infections was dependent on increased T-bet expression because T-bet+/− cells were resistant to these phenotypic changes. Larger numbers of pre-existing memory CD8 T cells limited the duration of 2o infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2o TE CD8 T cells that formed. Together, these data show that, over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with antigen or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by pre-existing memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies. PMID:21930973

  7. Significant Artifact Reduction at 1.5T and 3T MRI by the Use of a Cochlear Implant with Removable Magnet: An Experimental Human Cadaver Study

    PubMed Central

    Wagner, Franca; Wimmer, Wilhelm; Leidolt, Lars; Vischer, Mattheus; Weder, Stefan; Wiest, Roland; Mantokoudis, Georgios; Caversaccio, Marco D.

    2015-01-01

    Objective Cochlear implants (CIs) are standard treatment for postlingually deafened individuals and prelingually deafened children. This human cadaver study evaluated diagnostic usefulness, image quality and artifacts in 1.5T and 3T magnetic resonance (MR) brain scans after CI with a removable magnet. Methods Three criteria (diagnostic usefulness, image quality, artifacts) were assessed at 1.5T and 3T in five cadaver heads with CI. The brain magnetic resonance scans were performed with and without the magnet in situ. The criteria were analyzed by two blinded neuroradiologists, with focus on image distortion and limitation of the diagnostic value of the acquired MR images. Results MR images with the magnet in situ were all compromised by artifacts caused by the CI. After removal of the magnet, MR scans showed an unequivocal artifact reduction with significant improvement of the image quality and diagnostic usefulness, both at 1.5T and 3T. Visibility of the brain stem, cerebellopontine angle, and parieto-occipital lobe ipsilateral to the CI increased significantly after magnet removal. Conclusions The results indicate the possible advantages for 1.5T and 3T MR scanning of the brain in CI carriers with removable magnets. Our findings support use of CIs with removable magnets, especially in patients with chronic intracranial pathologies. PMID:26200775

  8. Significant Artifact Reduction at 1.5T and 3T MRI by the Use of a Cochlear Implant with Removable Magnet: An Experimental Human Cadaver Study.

    PubMed

    Wagner, Franca; Wimmer, Wilhelm; Leidolt, Lars; Vischer, Mattheus; Weder, Stefan; Wiest, Roland; Mantokoudis, Georgios; Caversaccio, Marco D

    2015-01-01

    Cochlear implants (CIs) are standard treatment for postlingually deafened individuals and prelingually deafened children. This human cadaver study evaluated diagnostic usefulness, image quality and artifacts in 1.5T and 3T magnetic resonance (MR) brain scans after CI with a removable magnet. Three criteria (diagnostic usefulness, image quality, artifacts) were assessed at 1.5T and 3T in five cadaver heads with CI. The brain magnetic resonance scans were performed with and without the magnet in situ. The criteria were analyzed by two blinded neuroradiologists, with focus on image distortion and limitation of the diagnostic value of the acquired MR images. MR images with the magnet in situ were all compromised by artifacts caused by the CI. After removal of the magnet, MR scans showed an unequivocal artifact reduction with significant improvement of the image quality and diagnostic usefulness, both at 1.5T and 3T. Visibility of the brain stem, cerebellopontine angle, and parieto-occipital lobe ipsilateral to the CI increased significantly after magnet removal. The results indicate the possible advantages for 1.5T and 3T MR scanning of the brain in CI carriers with removable magnets. Our findings support use of CIs with removable magnets, especially in patients with chronic intracranial pathologies.

  9. London penetration depth measurements in Ba (Fe 1-xT x) 2As 2(T=Co,Ni,Ru,Rh,Pd,Pt,Co+Cu) superconductors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gordon, Ryan T.

    2011-01-01

    The London penetration depth has been measured in various doping levels of single crystals of Ba(Fe 1-xT x) 2As 2 (T=Co,Ni,Ru,Rh,Pd,Pt,Co+Cu) superconductors by utilizing a tunnel diode resonator (TDR) apparatus. All in-plane penetration depth measurements exhibit a power law temperature dependence of the form Δλ ab(T) = CT n, indicating the existence of low-temperature, normal state quasiparticles all the way down to the lowest measured temperature, which was typically 500 mK. Several different doping concentrations from the Ba(Fe 1-xT x) 2As 2 (T=Co,Ni) systems have been measured and the doping dependence of the power law exponent, n, is compared tomore » results from measurements of thermal conductivity and specific heat. In addition, a novel method has been developed to allow for the measurement of the zero temperature value of the in-plane penetration depth, λ ab(0), by using TDR frequency shifts. By using this technique, the doping dependence of λ ab(0) has been measured in the Ba(Fe 1-xCo x) 2As 2 series, which has allowed also for the construction of the doping-dependent superfluid phase stiffness, ρ s(T) = [λ(0)/λ(T)] 2. By studying the effects of disorder on these superconductors using heavy ion irradiation, it has been determined that the observed power law temperature dependence likely arises from pair-breaking impurity scattering contributions, which is consistent with the proposed s±-wave symmetry of the superconducting gap in the dirty scattering limit. This hypothesis is supported by the measurement of an exponential temperature dependence of the penetration depth in the intrinsically clean LiFeAs, indicative of a nodeless superconducting gap.« less

  10. Glasses of the As/sub 2/S/sub 3/-T1/sub 2/S system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gutenev, M.S.

    1986-08-01

    A dielcometric study of (AsS /SUB 1.5/ ) /SUB 1-x/ (TiS /SUB 0.5/ ) /SUB x/ (0 is less than or equal to x is less than or equal to 0.61) glasses was carried out. Glassforming alloys were prepared in thin-walled quartz ampules by rapid cooling from 700 C in air. The methods of determination of permittivity, refractive index, and density, the values of which are shown here, have been previously discussed. The molar infrared polarizability is calculated from the experimental data previously gathered, and the concentration dependence is shown. In this paper, the presence of chemical atomic order inmore » T1AsS/sub 2/ glass described by TISAsS /SUB 2/2/ structural units was experimentally proved. An assumption was made of strong mutual influence of T1AsS/sub 2/ and AsS /SUB 1.5/ complexes caused by coordination of thallium with bridging sulfur atoms.« less

  11. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510; Yoshizaki, Takayuki

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear.more » Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.« less

  12. 17 CFR 240.11a1-3(T) - Bona fide hedge transactions in certain securities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bona fide hedge transactions in certain securities. 240.11a1-3(T) Section 240.11a1-3(T) Commodity and Securities Exchanges... (rule 11a-1) § 240.11a1-3(T) Bona fide hedge transactions in certain securities. A bona fide hedge...

  13. 17 CFR 240.11a1-3(T) - Bona fide hedge transactions in certain securities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Bona fide hedge transactions in certain securities. 240.11a1-3(T) Section 240.11a1-3(T) Commodity and Securities Exchanges... (rule 11a-1) § 240.11a1-3(T) Bona fide hedge transactions in certain securities. A bona fide hedge...

  14. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun

    2011-06-17

    Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from themore » edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.« less

  15. Effect of Mangiferin and Mahanimbine on Glucose Utilization in 3T3-L1 cells.

    PubMed

    Kumar, B Dinesh; Krishnakumar, K; Jaganathan, Saravana Kumar; Mandal, Mahitosh

    2013-01-01

    Stem barks of Mangifera indica contain a rich content of mangiferin (xanthone glucoside), whereas Murraya koenigii leaves contain rich sources of mahanimbine (carbazole alkaloid) and used traditionally for the treatment of diabetes. To investigate the effects of mangiferin (xanthone glucoside) and mahanimbine (carbazole alkaloid) on glucose utilization in 3T3-L1 cells. Mangiferin was isolated from stem barks of Mangifera indica and mahanimbine was isolated from Murraya koenigii leaves. These isolated compounds were subjected to MTT assay and glucose utilization test with 3T3-L1 cells. Treatment of the 3T3-L1 cells with mangiferin and mahanimbine increased the glucose utilization in a dose-dependent manner. At a concentration of 1 mM, mangniferin showed 2-fold increase in glucose utilization compared with untreated control. In case of mahanimbine, the observed effect at 1 mM was almost equivalent to positive control (insulin at 1 μM). Moreover, MTT assay showed that both of these compounds were less toxic at a concentration of 1 mM (nearly 75% cells are viable). The present results indicated that these natural products (mangiferin and mahanimbine) exhibited potential ethnomedical uses in management of diabetes.

  16. S1PR1 is crucial for accumulation of regulatory T cells in tumors via STAT3

    PubMed Central

    Priceman, Saul J.; Shen, Shudan; Wang, Lin; Deng, Jiehui; Yue, Chanyu; Kujawski, Maciej; Yu, Hua

    2014-01-01

    Summary S1PR1 signaling has been shown to restrain the number and function of Tregs in the periphery under physiological conditions and in colitis models, but its role in regulating tumor-associated T cells is unknown. Here, we show that S1PR1 signaling in T cells drives Treg accumulation in tumors, limits CD8+ T cell recruitment and activation, and promotes tumor growth. S1PR1 intrinsic in T cells affects Tregs, but not CD8+ T cells, as demonstrated by adoptive transfer models and transient pharmacological S1PR1 modulation. We further investigated the molecular mechanism(s) underlying S1PR1-mediated Treg accumulation in tumors, showing that increasing S1PR1 in CD4+ T cells promotes STAT3 activation and JAK/STAT3-dependent Treg tumor migration. Furthermore functionally ablating STAT3 in T cells diminishes tumor-associated Treg accumulation and tumor growth. Our study demonstrates a stark contrast of the consequences by the same signaling receptor, namely S1PR1, in regulating Tregs in the periphery and in tumors. PMID:24630990

  17. Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response

    PubMed Central

    Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

    2014-01-01

    Background. Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-β and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3+CTLA4+ Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation. PMID:25152568

  18. 26 CFR 1.6031(b)-2T - REMIC reporting requirements (temporary). [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements (temporary). [Reserved] ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false REMIC reporting requirements (temporary). [Reserved] 1.6031(b)-2T Section 1.6031(b)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  19. 3,3',5-triiodothyroxine inhibits apoptosis and oxidative stress by the PKM2/PKM1 ratio during oxygen-glucose deprivation/reperfusion AC16 and HCM-a cells: T3 inhibits apoptosis and oxidative stress by PKM2/PKM1 ratio.

    PubMed

    Li, Qi; Qi, Xin; Jia, Wenjun

    2016-06-17

    Oxidative stress (OS) plays a crucial role in the development of myocardial disease, which can induce the dysfunction of cardiac muscle cells. 3,3',5-triiodothyroxine (T3) is a hormone secreted from the thyroid gland that has been shown to protect cells by improving the redox state and to regulate the expression of pyruvate kinase muscle isozyme (PKM, including two isoforms PKM1 and PKM2). The present study aimed to reveal the key effects of T3 on protecting human myocardial cell lines from oxidative stress and the downstream molecular mechanism. An oxygen-glucose deprivation/reperfusion model (OGDR) and three subtypes of the deiodinase family (DIO1, DIO2, and DIO3), which convert thyroxine (T4) to T3, were tested in this model. Our results show that the expression of DIO1, DIO2 and T3 was downregulated, but DIO3 was upregulated in OGDR-treated AC16 and HCM-a cells. Then, OGDR-treated cells were treated with T3 and T4. The results show that T3 inhibited the expression of reactive oxygen species (ROS) and malonic dialdehyde (MDA), but upregulated glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The effects of T4 were not notable. T3 also protected OGDR cells from apoptosis and upregulated the PKM2/PKM1 ratio. Further mechanistic studies found that PKM2 inhibition by small interfering RNA (siRNA) could attenuate the anti-OS and anti-apoptotic effects of T3. These findings suggest that T3 can inhibit apoptosis and oxidative stress in OGDR-treated AC16 and HCM-a cells by regulating the PKM2/PKM1 ratio. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. CD4+ T Cells Reactive to Enteric Bacterial Antigens in Spontaneously Colitic C3H/HeJBir Mice: Increased T Helper Cell Type 1 Response and Ability to Transfer Disease

    PubMed Central

    Cong, Yingzi; Brandwein, Steven L.; McCabe, Robert P.; Lazenby, A.; Birkenmeier, Edward H.; Sundberg, John P.; Elson, Charles O.

    1998-01-01

    C3H/HeJBir mice are a new substrain that spontaneously develop colitis early in life. This study was done to determine the T cell reactivity of C3H/HeJBir mice to candidate antigens that might be involved in their disease. C3H/HeJBir CD4+ T cells were strongly reactive to antigens of the enteric bacterial flora, but not to epithelial or food antigens. The stimulatory material in the enteric bacteria was trypsin sensitive and restricted by class II major histocompatibility complex molecules, but did not have the properties of a superantigen. The precursor frequency of interleuken (IL)-2–producing, bacterial-reactive CD4+ T cells in colitic mice was 1 out of 2,000 compared to 1 out of 20,000–25,000 in noncolitic control mice. These T cells produced predominately IL-2 and interferon γ, consistent with a T helper type 1 cell response and were present at 3–4 wk, the age of onset of the colitis. Adoptive transfer of bacterial-antigen–activated CD4+ T cells from colitic C3H/HeJBir but not from control C3H/HeJ mice into C3H/HeSnJ scid/scid recipients induced colitis. These data represent a direct demonstration that T cells reactive with conventional antigens of the enteric bacterial flora can mediate chronic inflammatory bowel disease. PMID:9500788

  1. T1 and T2 mapping in myocarditis: seeing beyond the horizon of Lake Louise criteria and histopathology.

    PubMed

    Puntmann, Valentina O; Zeiher, Andreas M; Nagel, Eike

    2018-05-01

    Myocarditis and its sequelae remain an unconquered clinical problem, disproportionately affecting the young. Several hurdles beset myocarditis, including non-specific symptoms, heterogeneous clinical presentation, dynamic disease stages, underscored by an absence of an easy diagnostic test or a specific treatment. Areas covered: The current diagnostic means are poorly equipped to counter the challenge; the gold standard by invasive endomyocardial biopsy relies on availability of expert procedural and reading skill. The tissue diagnostic criteria were developed to improve readers agreement with clinical diagnosis, and not based on evidence for differential treatment or improved prognosis. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis. They require extensive imaging, which is insufficiently robust with poor diagnostic confidence and tissue pathophysiological validation; they similarly lack evidence of improved outcome by guiding clinical management. T1 and T2 mapping are a step-change, providing robust, short and quantifiable imaging application, which can veritably reflect the dynamic and heterogeneous underlying disease. Expert commentary: T1 and T2 mapping harbours a unique potential for an objective non-invasive disease recognition and treatment discovery in myocarditis. These measures should enter independently into clinical experimentation, with a high priority for outcome and therapeutic studies.

  2. Mitochondrial tRNALeu(UUR) C3275T, tRNAGln T4363C and tRNALys A8343G mutations may be associated with PCOS and metabolic syndrome.

    PubMed

    Ding, Yu; Xia, Bo-Hou; Zhang, Cai-Juan; Zhuo, Guang-Chao

    2018-02-05

    Polycystic ovary syndrome (PCOS) is a very prevalent endocrine disease affecting reproductive women. Clinically, patients with this disorder are more vulnerable to develop type 2 diabetes mellitus (T2DM), cardiovascular events, as well as metabolic syndrome (MetS). To date, the molecular mechanism underlying PCOS remains largely unknown. Previously, we showed that mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutation was an important cause for PCOS. In the current study, we described the clinical and biochemical features of a three-generation pedigree with maternally transmitted MetS, combined with PCOS. A total of three matrilineal relatives exhibited MetS including obesity, high triglyceride (TG) and Hemoglobin A1c (HbA1c) levels, and hypertension. Whereas one patient from the third generation manifestated PCOS. Mutational analysis of the whole mitochondrial genes from the affected individuals identified a set of genetic variations belonging to East Asia haplogroup B4b1c. Among these variants, the homoplasmic C3275T mutation disrupted a highly evolutionary conserved base-pairing (28A-46C) on the variable region of tRNA Leu(UUR) , whereas the T4363C mutation created a new base-pairing (31T-37A) in the anticodon stem of tRNA Gln , furthermore, the A8343G mutation occurred at the very conserved position of tRNA Lys and may result the failure in mitochondrial tRNAs (mt-tRNAs) metabolism. Biochemical analysis revealed the deficiency in mitochondrial functions including lower levels of mitochondrial membrane potential (MMP), ATP production and mtDNA copy number, while a significantly increased reactive oxygen species (ROS) generation was observed in polymononuclear leukocytes (PMNs) from the individuals carrying these mt-tRNA mutations, suggesting that these mutations may cause mitochondrial dysfunction that was responsible for the clinical phenotypes. Taken together, our data indicated that mt-tRNA mutations were associated with MetS and PCOS in this

  3. Phosphate (Pi)-regulated heterodimerization of the high-affinity sodium-dependent Pi transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular Pi sensing independently of Pi uptake.

    PubMed

    Bon, Nina; Couasnay, Greig; Bourgine, Annabelle; Sourice, Sophie; Beck-Cormier, Sarah; Guicheux, Jérôme; Beck, Laurent

    2018-02-09

    Extracellular phosphate (P i ) can act as a signaling molecule that directly alters gene expression and cellular physiology. The ability of cells or organisms to detect changes in extracellular P i levels implies the existence of a P i -sensing mechanism that signals to the body or individual cell. However, unlike in prokaryotes, yeasts, and plants, the molecular players involved in P i sensing in mammals remain unknown. In this study, we investigated the involvement of the high-affinity, sodium-dependent P i transporters PiT1 and PiT2 in mediating P i signaling in skeletal cells. We found that deletion of PiT1 or PiT2 blunted the P i -dependent ERK1/2-mediated phosphorylation and subsequent gene up-regulation of the mineralization inhibitors matrix Gla protein and osteopontin. This result suggested that both PiTs are necessary for P i signaling. Moreover, the ERK1/2 phosphorylation could be rescued by overexpressing P i transport-deficient PiT mutants. Using cross-linking and bioluminescence resonance energy transfer approaches, we found that PiT1 and PiT2 form high-abundance homodimers and P i -regulated low-abundance heterodimers. Interestingly, in the absence of sodium-dependent P i transport activity, the PiT1-PiT2 heterodimerization was still regulated by extracellular P i levels. Of note, when two putative P i -binding residues, Ser-128 (in PiT1) and Ser-113 (in PiT2), were substituted with alanine, the PiT1-PiT2 heterodimerization was no longer regulated by extracellular P i These observations suggested that P i binding rather than P i uptake may be the key factor in mediating P i signaling through the PiT proteins. Taken together, these results demonstrate that P i -regulated PiT1-PiT2 heterodimerization mediates P i sensing independently of P i uptake. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression.

    PubMed

    Franciosa, G; Diluvio, G; Gaudio, F Del; Giuli, M V; Palermo, R; Grazioli, P; Campese, A F; Talora, C; Bellavia, D; D'Amati, G; Besharat, Z M; Nicoletti, C; Siebel, C W; Choy, L; Rustighi, A; Sal, G Del; Screpanti, I; Checquolo, S

    2016-09-08

    Deregulated Notch signaling is associated with T-cell Acute Lymphoblastic Leukemia (T-ALL) development and progression. Increasing evidence reveals that Notch pathway has an important role in the invasion ability of tumor cells, including leukemia, although the underlying molecular mechanisms remain mostly unclear. Here, we show that Notch3 is a novel target protein of the prolyl-isomerase Pin1, which is able to regulate Notch3 protein processing and to stabilize the cleaved product, leading to the increased expression of the intracellular domain (N3IC), finally enhancing Notch3-dependent invasiveness properties. We demonstrate that the combined inhibition of Notch3 and Pin1 in the Notch3-overexpressing human leukemic TALL-1 cells reduces their high invasive potential, by decreasing the expression of the matrix metalloprotease MMP9. Consistently, Pin1 depletion in a mouse model of Notch3-induced T-ALL, by reducing N3IC expression and signaling, impairs the expansion/invasiveness of CD4(+)CD8(+) DP cells in peripheral lymphoid and non-lymphoid organs. Notably, in in silico gene expression analysis of human T-ALL samples we observed a significant correlation between Pin1 and Notch3 expression levels, which may further suggest a key role of the newly identified Notch3-Pin1 axis in T-ALL aggressiveness and progression. Thus, combined suppression of Pin1 and Notch3 proteins may be exploited as an additional target therapy for T-ALL.

  5. Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression

    PubMed Central

    Franciosa, G; Diluvio, G; Gaudio, F Del; Giuli, M V; Palermo, R; Grazioli, P; Campese, A F; Talora, C; Bellavia, D; D'Amati, G; Besharat, Z M; Nicoletti, C; Siebel, C W; Choy, L; Rustighi, A; Sal, G Del; Screpanti, I; Checquolo, S

    2016-01-01

    Deregulated Notch signaling is associated with T-cell Acute Lymphoblastic Leukemia (T-ALL) development and progression. Increasing evidence reveals that Notch pathway has an important role in the invasion ability of tumor cells, including leukemia, although the underlying molecular mechanisms remain mostly unclear. Here, we show that Notch3 is a novel target protein of the prolyl-isomerase Pin1, which is able to regulate Notch3 protein processing and to stabilize the cleaved product, leading to the increased expression of the intracellular domain (N3IC), finally enhancing Notch3-dependent invasiveness properties. We demonstrate that the combined inhibition of Notch3 and Pin1 in the Notch3-overexpressing human leukemic TALL-1 cells reduces their high invasive potential, by decreasing the expression of the matrix metalloprotease MMP9. Consistently, Pin1 depletion in a mouse model of Notch3-induced T-ALL, by reducing N3IC expression and signaling, impairs the expansion/invasiveness of CD4+CD8+ DP cells in peripheral lymphoid and non-lymphoid organs. Notably, in in silico gene expression analysis of human T-ALL samples we observed a significant correlation between Pin1 and Notch3 expression levels, which may further suggest a key role of the newly identified Notch3-Pin1 axis in T-ALL aggressiveness and progression. Thus, combined suppression of Pin1 and Notch3 proteins may be exploited as an additional target therapy for T-ALL. PMID:26876201

  6. Automated segmentation of multifocal basal ganglia T2*-weighted MRI hypointensities

    PubMed Central

    Glatz, Andreas; Bastin, Mark E.; Kiker, Alexander J.; Deary, Ian J.; Wardlaw, Joanna M.; Valdés Hernández, Maria C.

    2015-01-01

    Multifocal basal ganglia T2*-weighted (T2*w) hypointensities, which are believed to arise mainly from vascular mineralization, were recently proposed as a novel MRI biomarker for small vessel disease and ageing. These T2*w hypointensities are typically segmented semi-automatically, which is time consuming, associated with a high intra-rater variability and low inter-rater agreement. To address these limitations, we developed a fully automated, unsupervised segmentation method for basal ganglia T2*w hypointensities. This method requires conventional, co-registered T2*w and T1-weighted (T1w) volumes, as well as region-of-interest (ROI) masks for the basal ganglia and adjacent internal capsule generated automatically from T1w MRI. The basal ganglia T2*w hypointensities were then segmented with thresholds derived with an adaptive outlier detection method from respective bivariate T2*w/T1w intensity distributions in each ROI. Artefacts were reduced by filtering connected components in the initial masks based on their standardised T2*w intensity variance. The segmentation method was validated using a custom-built phantom containing mineral deposit models, i.e. gel beads doped with 3 different contrast agents in 7 different concentrations, as well as with MRI data from 98 community-dwelling older subjects in their seventies with a wide range of basal ganglia T2*w hypointensities. The method produced basal ganglia T2*w hypointensity masks that were in substantial volumetric and spatial agreement with those generated by an experienced rater (Jaccard index = 0.62 ± 0.40). These promising results suggest that this method may have use in automatic segmentation of basal ganglia T2*w hypointensities in studies of small vessel disease and ageing. PMID:25451469

  7. Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241

    PubMed Central

    Zhang, Liaoyuan; Guo, Zewang; Chen, Jiebo; Xu, Quanming; Lin, Hui; Hu, Kaihui; Guan, Xiong; Shen, Yaling

    2016-01-01

    Serratia sp. T241, a newly isolated xylose-utilizing strain, produced three 2,3-butanediol (2,3-BD) stereoisomers. In this study, three 2,3-butanediol dehydrogenases (BDH1-3) and one glycerol dehydrogenase (GDH) involved in 2,3-BD isomers formation by Serratia sp. T241 were identified. In vitro conversion showed BDH1 and BDH2 could catalyzed (3S)-acetoin and (3R)-acetoin into (2S,3S)-2,3-BD and meso-2,3-BD, while BDH3 and GDH exhibited the activities from (3S)-acetoin and (3R)-acetoin to meso-2,3-BD and (2R,3R)-2,3-BD. Four encoding genes were assembled into E. coli with budA (acetolactate decarboxylase) and budB (acetolactate synthase), responsible for converting pyruvate into acetoin. E. coli expressing budAB-bdh1/2 produced meso-2,3-BD and (2S,3S)-2,3-BD. Correspondingly, (2R,3R)-2,3-BD and meso-2,3-BD were obtained by E. coli expressing budAB-bdh3/gdh. These results suggested four enzymes might contribute to 2,3-BD isomers formation. Mutants of four genes were developed in Serratia sp. T241. Δbdh1 led to reduced concentration of meso-2,3-BD and (2S,3S)-2,3-BD by 97.7% and 87.9%. (2R,3R)-2,3-BD with a loss of 73.3% was produced by Δbdh3. Enzyme activity assays showed the decrease of 98.4% and 22.4% by Δbdh1 and Δbdh3 compared with the wild strain. It suggested BDH1 and BDH3 played important roles in 2,3-BD formation, BDH2 and GDH have small effects on 2,3-BD production by Serratia sp. T241. PMID:26753612

  8. Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241.

    PubMed

    Zhang, Liaoyuan; Guo, Zewang; Chen, Jiebo; Xu, Quanming; Lin, Hui; Hu, Kaihui; Guan, Xiong; Shen, Yaling

    2016-01-12

    Serratia sp. T241, a newly isolated xylose-utilizing strain, produced three 2,3-butanediol (2,3-BD) stereoisomers. In this study, three 2,3-butanediol dehydrogenases (BDH1-3) and one glycerol dehydrogenase (GDH) involved in 2,3-BD isomers formation by Serratia sp. T241 were identified. In vitro conversion showed BDH1 and BDH2 could catalyzed (3S)-acetoin and (3R)-acetoin into (2S,3S)-2,3-BD and meso-2,3-BD, while BDH3 and GDH exhibited the activities from (3S)-acetoin and (3R)-acetoin to meso-2,3-BD and (2R,3R)-2,3-BD. Four encoding genes were assembled into E. coli with budA (acetolactate decarboxylase) and budB (acetolactate synthase), responsible for converting pyruvate into acetoin. E. coli expressing budAB-bdh1/2 produced meso-2,3-BD and (2S,3S)-2,3-BD. Correspondingly, (2R,3R)-2,3-BD and meso-2,3-BD were obtained by E. coli expressing budAB-bdh3/gdh. These results suggested four enzymes might contribute to 2,3-BD isomers formation. Mutants of four genes were developed in Serratia sp. T241. Δbdh1 led to reduced concentration of meso-2,3-BD and (2S,3S)-2,3-BD by 97.7% and 87.9%. (2R,3R)-2,3-BD with a loss of 73.3% was produced by Δbdh3. Enzyme activity assays showed the decrease of 98.4% and 22.4% by Δbdh1 and Δbdh3 compared with the wild strain. It suggested BDH1 and BDH3 played important roles in 2,3-BD formation, BDH2 and GDH have small effects on 2,3-BD production by Serratia sp. T241.

  9. Bi-2212/1T-TaS2 Van der Waals junctions: Interplay of proximity induced high-T c superconductivity and CDW order.

    PubMed

    Li, Ang J; Zhu, Xiaochen; Stewart, G R; Hebard, Arthur F

    2017-07-05

    Understanding the coexistence, competition and/or cooperation between superconductivity and charge density waves (CDWs) in the transition metal dichalcogenides (TMDs) is an elusive goal which, when realized, promises to reveal fundamental information on this important class of materials. Here, we use four-terminal current-voltage measurements to study the Van der Waals interface between freshly exfoliated flakes of the high-T c superconductor, Bi-2212, and the CDW-dominated TMD layered material, 1T-TaS 2 . For highly transparent barriers, there is a pronounced Andreev reflection feature providing evidence for proximity-induced high-T c superconductivity in 1T-TaS 2 with a surprisingly large energy gap (~20 meV) equal to half that of intrinsic Bi-2212 (~40 meV). Our systematic study using conductance spectroscopy of junctions with different transparencies also reveals the presence of two separate boson modes, each associated with a "dip-hump" structure. We infer that the proximity-induced high-T c superconductivity in the 1T-TaS 2 is driven by coupling to the metastable metallic phase coexisting within the Mott commensurate CDW (CCDW) phase and associated with a concomitant change of the CCDW order parameter in the interfacial region.

  10. Oleoyl-L-carnitine inhibits glycine transport by GlyT2

    PubMed Central

    Carland, JE; Mansfield, RE; Ryan, RM; Vandenberg, RJ

    2013-01-01

    Background and Purpose Concentrations of extracellular glycine in the CNS are regulated by two Na+/Cl–-dependent glycine transporters, GlyT1 and GlyT2. Selective inhibitors of GlyT1 have been developed for the treatment of schizophrenia, whilst selective inhibitors of GlyT2 are analgesic in animal models of pain. We have assessed a series of endogenous lipids as inhibitors of GlyT1 and GlyT2. Experimental Approach Human GlyT1 and GlyT2 were expressed in Xenopus laevis oocytes, and the inhibitory actions of a series of acylcarnitines on glycine transport were measured using electrophysiological techniques. Key Results Oleoyl-l-carnitine inhibited glycine transport by GlyT2, with an IC50 of 340 nM, which is 15-fold more potent than the previously identified lipid inhibitor N-arachidonyl-glycine. Oleoyl-l-carnitine had a slow onset of inhibition and a slow washout. Using a series of chimeric GlyT1/2 transporters and point mutant transporters, we have identified an isoleucine residue in extracellular loop 4 of GlyT2 that conferred differences in sensitivity to oleoyl-l-carnitine between GlyT2 and GlyT1. Conclusions and Implications Oleoyl-l-carnitine is a potent non-competitive inhibitor of GlyT2. Previously identified GlyT2 inhibitors show potential as analgesics and the identification of oleoyl-l-carnitine as a novel GlyT2 inhibitor may lead to new ways of treating pain. PMID:22978602

  11. Tumor-penetrating Peptide Conjugated and Doxorubicin Loaded T1-T2 Dual Mode MRI Contrast Agents Nanoparticles for Tumor Theranostics

    PubMed Central

    Gao, Lipeng; Yu, Jing; Liu, Yang; Zhou, Jinge; Sun, Lei; Wang, Jing; Zhu, Jianzhong; Peng, Hui; Lu, Weiyue; Yu, Lei; Yan, Zhiqiang; Wang, Yiting

    2018-01-01

    The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. Methods: In this study, a tumor-penetrating peptide RGERPPR (RGE) modified, Gd-DTPA conjugated, and doxorubicin (DOX) loaded Fe3O4@SiO2@mSiO2 nanoparticle drug delivery system (Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs) was prepared for tumor theranostics. Results: The Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs showed a z-average hydrodynamic diameter of about 90 nm, and a pH-sensitive DOX release profile. The 3 T MRI results confirmed the relaxivity of the NPs (r1 = 6.13 mM-1S-1, r2 = 36.89 mM-1S-1). The in vitro cellular uptake and cytotoxicity assays on U87MG cells confirmed that the conjugation of RGERPPR played a significant role in increasing the cellular uptake and cytotoxicity of the NPs. The near-infrared fluorescence in vivo imaging results showed that the NPs could be significantly accumulated in the U87MG tumor tissue, which should result from the mediation of the tumor-penetrating peptide RGERPPR. The MRI results showed that the NPs offered a T1-T2 dual mode contrast imaging effect which would lead to a more precise diagnosis. Compared with unmodified NPs, the RGE-modified NPs showed significantly enhanced MR imaging signal in tumor tissue and antitumor effect, which should also be attributed to the tumor penetrating ability of RGERPPR peptide. Furthermore, the Hematoxylin and Eosin (H&E) staining and TUNEL assay proved that the NPs produced obvious cell apoptosis in tumor tissue. Conclusions: These results indicated that Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs are an effective targeted delivery system for tumor theranostics, and should have a potential value in the personalized treatment of tumor. PMID:29290795

  12. 26 CFR 1.25-2T - Amount of credit (Temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Changes in Rates During A Taxable Year § 1.25-2T Amount of credit (Temporary). (a) In general. Except as... average annual aggregate principal amount of mortgages executed during the immediately preceding 3... that the weighted average of the certificate credit rates in such mortgage credit certificate program...

  13. Reconstruction, thermodynamics and stability of the ΛCDM model in f(T,{ T }) gravity

    NASA Astrophysics Data System (ADS)

    Junior, Ednaldo L. B.; Rodrigues, Manuel E.; Salako, Ines G.; Houndjo, Mahouton J. S.

    2016-06-01

    We reconstruct the ΛCDM model for f(T,{ T }) theory, where T is the torsion scalar and { T } the trace of the energy-momentum tensor. The result shows that the action of ΛCDM is a combination of a linear term, a constant (-2{{Λ }}) and a nonlinear term given by the product \\sqrt{-T}{F}g[({T}1/3/16π G) (16π G{ T }+T+8{{Λ }})], with F g being a generic function. We show that to maintain conservation of the energy-momentum tensor, we should impose that {F}g[y] must be linear on the trace { T }. This reconstruction decays in f (T) theory for {F}g\\equiv Q, with Q a constant. Our reconstruction describes the cosmological eras to the present time. The model present stability within the geometric and matter perturbations for the choice {F}g=y, where y=({T}1/3/16π G)(16π G{ T }+T+8{{Λ }}), except for the geometric part in the de Sitter model. We impose the first and second laws of thermodynamics to ΛCDM and find the condition where they are satisfied, that is, {T}A,{G}{{eff}}\\gt 0, however where this is not possible in the cases that we choose, this leads to a breakdown of positive entropy and Misner-Sharp energy.

  14. Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes.

    PubMed

    Pagano, Eleonora; Coso, Omar; Calvo, Juan Carlos

    2008-05-01

    The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 cells as model, we demonstrate that EGF (10 nM, 5 min) in addition to stimulate receptor tyrosine phosphorylation of both erbB2 and EGFR, is able to induce the heterodimer erbB2-EGFR. We treated proliferating 3T3-L1 cells with two inhibitors, AG 825 (IC(50) 0.35 microM, 54 times more selective for erbB2 than for EGFR, IC(50) 19 microM), and AG 879 (IC(50) of 1 microM for erbB2 versus 500 microM for EGFR). We found that both inhibited the proliferation on a dose-dependent basis, reaching a 30% maximal inhibition at 100 microM (P < 0.001) for AG825, and a 20% maximal inhibition at 10 microM (P < 0.001) for AG 879. These results involve erbB2 in 3T3-L1 proliferation. When studying the differentiation process, we found that the action of MIX-Dexa immediately activates MEK, JNK and p38 kinases. We observed that PD98059 and SP600125 (MEK-ERK and JNK inhibitors, respectively) added 1 h prior to the MIX-Dexa induction produced a decrease in erbB2 expression after 6 h, which is even greater than the one produced by the inducers, MIX-Dexa. This work supports erbB2 as a key factor in 3T3-L1 adipogenesis, acting mostly and not only during the proliferative phase but also during the differentiation through modulation of both its expression and activity.

  15. Measurement of the ratio $$B(t \\to W b)/B(t \\to W q)$$ in $$t\\bar{t}$$ dilepton channel at CDF

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galloni, Camilla

    2012-01-01

    My analysis is based on the number of b-jets found in t¯t events using the dilepton sample with at least 2 jets in the final state. The charged leptons could be either electrons or muons. Tau leptons are not included. We use SecVtx algorithm, based on the reconstruction of a secondary vertex in the event, in order to identify a jet coming from b-quark fragmentation (b-tagging). Due to the high purity of the t¯t signal in dilepton events it is possible to perform a kinematic measurement of the t¯t cross section. Our strategy is to use this result to makemore » prediction on the number of t¯t events. We divide our sample in subsets according to dilepton type (combination of the lepton type), number of jets in the final states and events with zero, one or two tags. The comparison between events and the prediction, given by the sum of the expected t¯t estimate and the background yield, in each subsample is made using a Likelihood function. Our measured value for R is the one which maximizes the Likelihood, i.e. gives the best match between our expectation and the observed data. We measure: p¯p!t¯t = 7.05±0.53stat±0.42lumi , R= 0.86±0.06 (stat+syst) and, in the hypothesis of CKM matrix unitarity with three quark generations, | Vtb | = 0.93 ± 0.03. Our analysis on the p¯p!t¯t was performed independently of the official dilepton analisys on the t¯t production cross section. So it represents also a valuable crosscheck for the official analysis. In chapter 1, a brief introduction to the theoretical framework is given. The standard model of elementary particles and the Quantum Cromodynamic theories are introduced. Then the top quark is presented, with a short descpription of its properties, as its mass, its production mode and its cross section. Some previous results on R are listed as well. Later we present the experiment that collected our data, both the collider (chapter 2) and the detector (CDF)(chapter 3). In chapter 4 we describe the physics object

  16. Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels.

    PubMed

    Uduak, Okon Akpan; Ani, Elemi John; Etoh, Emmauel Columba Inyang; Macstephen, Adienbo Ologbagno

    2014-05-01

    There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels. To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH. Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control. These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB.

  17. Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels

    PubMed Central

    Uduak, Okon Akpan; Ani, Elemi John; Etoh, Emmauel Columba Inyang; Macstephen, Adienbo Ologbagno

    2014-01-01

    Background: There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels. Objective: To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH. Materials and Methods: Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. Results: The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control. Conclusion: These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB. PMID:25013255

  18. Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

    PubMed

    Cuny, F; Géry, B; Florescu, C; Clarisse, B; Blanchard, D; Rame, J-P; Babin, E; De Raucourt, D

    2013-11-01

    Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. CLCC François-Baclesse and CHU de Caen. Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Biosensor for the enantioselective analysis of the thyroid hormones (+)-3,3',5-triiodo-L-thyronine (T3) and (+)-3,3',5,5'-tetraiodo-L-thyronine (T4).

    PubMed

    Aboul-Enein, Hassan V; Stefan, Raluca-Ioana; Litescu, Simona; Radu, Gabriel Lucian

    2002-01-01

    An amperometric biosensor based on L-aminoacid oxidase is proposed for enantioselective assay of (+)-3,3',5-triiodo-L-thyronine (L-T3) and (+)-3,3',5,5'-tetraiodo-L-thyronine (L-T4), due to the fact that only the L enantiomer has the hormonal activity. The construction of the amperometric biosensor is simple and reproducible. The analytical information obtained from enantioselective analysis are reliable. The RSD <1% assured by using the amperometric biosensors for L enantiomers assay as raw materials, and from tablets, demonstrated their suitability for the analysis of T3 and T4 at ppb concentration levels.

  20. Comparative study of microelectrode recording-based STN location and MRI-based STN location in low to ultra-high field (7.0 T) T2-weighted MRI images

    NASA Astrophysics Data System (ADS)

    Verhagen, Rens; Schuurman, P. Richard; van den Munckhof, Pepijn; Fiorella Contarino, M.; de Bie, Rob M. A.; Bour, Lo J.

    2016-12-01

    Objective. The correspondence between the anatomical STN and the STN observed in T2-weighted MRI images used for deep brain stimulation (DBS) targeting remains unclear. Using a new method, we compared the STN borders seen on MRI images with those estimated by intraoperative microelectrode recordings (MER). Approach. We developed a method to automatically generate a detailed estimation of STN shape and the location of its borders, based on multiple-channel MER measurements. In 33 STNs of 19 Parkinson patients, we quantitatively compared the dorsal and lateral borders of this MER-based STN model with the STN borders visualized by 1.5 T (n = 14), 3.0 T (n = 10) and 7.0 T (n = 9) T2-weighted MRI. Main results. The dorsal border was identified more dorsally on coronal T2 MRI than by the MER-based STN model, with a significant difference in the 3.0 T (range 0.97-1.19 mm) and 7.0 T (range 1.23-1.25 mm) groups. The lateral border was significantly more medial on 1.5 T (mean: 1.97 mm) and 3.0 T (mean: 2.49 mm) MRI than in the MER-based STN; a difference that was not found in the 7.0 T group. Significance. The STN extends further in the dorsal direction on coronal T2 MRI images than is measured by MER. Increasing MRI field strength to 3.0 T or 7.0 T yields similar discrepancies between MER and MRI at the dorsal STN border. In contrast, increasing MRI field strength to 7.0 T may be useful for identification of the lateral STN border and thereby improve DBS targeting.