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Browning J.D.,University of Texas Southwestern Medical Center | Browning J.D.,Advanced Imaging Research Center | Baker J.A.,University of Texas Southwestern Medical Center | Rogers T.,University of Texas Southwestern Medical Center | And 3 more authors.
American Journal of Clinical Nutrition | Year: 2011

Background: Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipo-genesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction. Objective: The aim of this study was to determine the effectiveness of 2 wk of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in subjects with NAFLD. Design: Eighteen NAFLD subjects (n = 5 men and 13 women) with a mean (±SD) age of 45 ± 12 y and a body mass index (in kg/m1) of 35 ± 7 consumed a carbohydrate-restricted (<20 g/d) or calorie-restricted (1200-1500 kcal/d) diet for 2 wk. Hepatic triglycerides were measured before and after intervention by magnetic resonance spectroscopy. Results: Mean (±SD) weight loss was similar between the groups (-4.0 ± 1.5 kg in the calorie-restricted group and -4.6 ± 1.5 kg in the carbohydrate-restricted group; P = 0.363). Liver triglycerides decreased significantly with weight loss (P < 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects (-55 ± 14%) than in calorie-restricted subjects (-28 ± 23%). Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = -0.606, P = 0.008), posttreatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = -0.191, P < 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P < 0.001). Conclusions: Two weeks of dietary intervention (=4.3% weight loss) reduced hepatic triglycerides by =42% in subjects with NAFLD; however, reductions were significantly greater with dietary carbohydrate restriction than with calorie restriction. This may have been due, in part, to enhanced hepatic and whole-body oxidation. © 2011 American Society for Nutrition. Source


Hooks J.C.,Advanced Imaging Research Center
Biopolymers | Year: 2011

Multimeric interactions that occur in biology provide impetus for chemists to explore new types of synthetic multivalent ligands that alter cellular functions by mechanisms inaccessible to natural substances. While many different molecules such as peptides, antibody fragments, carbohydrates and organic moieties have been used in developing multimeric ligands, it is worth exploring other important molecular types that have hardly been tested in developing multimeric compounds. Peptoids are one such class of compounds with highly facile synthesis as well as much better biologically amenable qualities. Recently, we identified two HCC4017 lung cancer cell targeting peptoids. Here we explore the possibility of synthesizing multimers of these compounds completely through a solid phase synthesis approach. We have synthesized mini-libraries of homodimers, homotrimers and most importantly, heterodimers of our lung cancer specific compounds. The idea is to develop series of compounds that only differs by the linker portion, which is readily adjustable within the library. The purpose of this is to find the optimal distance between each monomeric unit of the multimer that allows them to perfectly interact with their individual biological targets displayed on the cell surface. Future screens of these minilibraries will identify the multimers with improved binding affinities. Source


Krishnamurthy L.C.,Advanced Imaging Research Center | Krishnamurthy L.C.,University of Texas at Arlington | Liu P.,Advanced Imaging Research Center | Ge Y.,New York University | Lu H.,Advanced Imaging Research Center
Magnetic Resonance in Medicine | Year: 2014

Purpose Measurement of venous oxygenation (Yv) is a critical step toward quantitative assessment of brain oxygen metabolism, a key index in many brain disorders. The present study aims to develop a noninvasive, rapid, and reproducible method to measure Yv in a vessel-specific manner. Theory The method, T2-Relaxation-Under-Phase-Contrast MRI, utilizes complex subtraction of phase-contrast to isolate pure blood signal, applies nonslice-selective T2-preparation to measure T2, and converts T2 to oxygenation using a calibration plot. Methods Following feasibility demonstration, several technical aspects were examined, including validation with an established global Yv technique, test-retest reproducibility, sensitivity to detect oxygenation changes due to hypoxia and caffeine challenges, applicability of echo-planar-imaging (EPI) acquisition to shorten scan duration, and ability to study veins with a caliber of 1-2 mm. Results T2-Relaxation-Under-Phase-Contrast was able to simultaneously measure Yv in all major veins in the brain, including sagittal sinus, straight sinus, great vein, and internal cerebral vein. T 2-Relaxation-Under-Phase-Contrast results showed an excellent agreement with the reference technique, high sensitivity to oxygenation changes, and test-retest variability of 3.5 ± 1.0%. The use of segmented-EPI was able to reduce the scan duration to 1.5 minutes. It was also feasible to study pial veins and deep veins. Conclusion T2-Relaxation-Under-Phase- Contrast MRI is a promising technique for vessel-specific oxygenation measurement. © 2013 Wiley Periodicals, Inc. Source


Togao O.,Advanced Imaging Research Center | Doi S.,Southwestern Medical Center | Kuro-o M.,Southwestern Medical Center | Masaki T.,Advanced Imaging Research Center | Takahashi M.,Kure kyosai Hospital
Radiology | Year: 2010

Purpose: To test, in a murine model of unilateral ureteral obstruction (UUO), whether the magnetic resonance (MR) imaging-derived apparent diffusion coefficient (ADC) changes during the progression of renal fibrosis and correlates with the histopathologic changes observed in renal fibrogenesis. Materials and Methods: This study was approved by the institutional animal care and use committee. A UUO was created in each of 14 mice. In five mice, longitudinal diffusion-weighted (DW) imaging was performed before the UUO (day 0) and on days 3 and 7 after the UUO and was followed by histopathologic analysis. The nine remaining mice were examined with cross-sectional studies on days 0 ( n = 4) and 3 ( n = 5). ADCs were measured with a spin-echo echo-planar sequence at five b values ranging from 350 to 1200 sec/mm2. Differences in ADC among the time points and between the sides were assessed by using Tukey-Kramer and Student t tests, respectively. ADC was correlated with cell density and α-smooth muscle actin (α-SMA, a marker of myofibroblasts) expression at linear regression analysis. Results: Histopathologic examination revealed typical renal fibrosis on the side with UUO. The ADC decreased over time on the UUO side, from (1.02 ± 0.06 [standard deviation]) x 10-3 mm2/sec on day 0 to (0.70 ± 0.08) x 10-3 mm2/sec on day 3 (P < .001) and (0.57 ± 0.10) x 10-3 mm2/sec on day 7 (P < .001). The percentage change in ADC was greater on the UUO side than on the contralateral side on days 3 (29% ± 9, P = .05) and 7 (44% ± 11, P < .01). ADC correlated with both increased cell density and increased α-SMA expression (P < .001 for both correlations). Conclusion: An ADC decrease in renal fibrosis is associated with an increased number of cells, including fibroblasts. ADC has the potential to serve as a sensitive noninvasive biomarker of renal fibrosis. © RSNA, 2010. Source


Lu H.,Advanced Imaging Research Center | Yezhuvath U.S.,Advanced Imaging Research Center | Xiao G.,University of Texas Southwestern Medical Center
Human Brain Mapping | Year: 2010

The power of fMRI in assessing neural activities is hampered by inter-subject variations in basal physiologic parameters, which may not be related to neural activation but has a modulatory effect on fMRI signals. Therefore, normalization of fMRI signals with these parameters is useful in reducing variations and improving sensitivity of this important technique. Recently, we have shown that basal venous oxygenation is a significant modulator of fMRI signals and individuals with higher venous oxygenation tend to have lower fMRI signals. In this study, we aim to test the utility of venous oxygenation normalization in distinguishing subject groups. A "model" condition was used in which two visual stimuli with different flashing frequencies were used to stimulate two subject groups, respectively, thereby simulating the situation of control and patient groups. It was found that visualevoked BOLD signal is significantly correlated with baseline venous T2 (P 1/4 0.0003) and inclusion of physiologic modulator in the regression analysis can substantially reduce P values of group-level statistical tests. When applied to voxel-wise analysis, the normalization process can allow the detection of more significant voxels. The utility of other basal parameters, including blood pressure, heart rate, arterial oxygenation, and end-tidal CO2, in BOLD normalization was also assessed and it was found that the improvement was less significant. Time-to-peak of the BOLD responses was also studied and it was found that subjects with higher basal venous oxygenation tend to slower BOLD responses. © 2009 Wiley-Liss, Inc. Source

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