Biomedical subjects

Jinghua Wang

Publications and source records attributed to Jinghua Wang.

At least 19 recordsLinked to original sources

PubMed2007

Transcriptional and epigenetic regulation of interleukin-2 gene in activated T cells by morphine.

Chronic morphine inhibits interleukin-2 (IL-2) at both the transcriptional and protein synthesis levels. The molecular mechanisms by which morphine decreases IL-2 are not fully understood. The production of IL-2 is tightly regulated by several transcription factors that bind to the IL-2 promoter. Herein, we show that chronic morphine treatment results in an increase in cAMP levels with a concurrent up-regulation of the cAMP inducible repressor inducible cAMP early repressor (ICER)/cAMP response element modulator (CREM) and down-regulation of p-cAMP-response element-binding protein (CREB) in activated T cells. Furthermore, ICER competes for p-CREB binding to the cAMP-responsive elements (CREs) site. This leads to the uncoupling of CBP/p300 thereby abrogating IL-2 transcription. Overexpression of either antisense CREM or CREB plasmid rescued morphine-induced inhibition of IL-2 promoter activity and protein production. In addition, we also found that chronic morphine treatment inhibited the acetylation and trimethylation of histones and decreased both DNA demethylation and accessibility of the IL-2 promoter. These findings suggest that chronic morphine treatment may function through both transcriptional and epigenetic mechanisms to inhibit IL-2 production.

Animals↗

PubMed2006

T1 measurements incorporating flip angle calibration and correction in vivo.

In this work, we propose a variable FA method that combines in vivo flip angle (FA) calibration and correction with a short TR variable FA approach for a fast and accurate T(1) mapping. The precision T(1)s measured across a uniform milk phantom is estimated to be 2.65% using the conventional (slow) inversion recovery (IR) method and 28.5% for the variable FA method without FA correction, and 2.2% when FA correction is included. These results demonstrate that the sensitivity of the variable FA method to RF nonuniformities can be dramatically reduced when these nonuniformities are directly measured and corrected. The acquisition time for this approach decreases to 10 min from 85 min for the conventional IR method. In addition, we report that the averaged T(1)s measured from five normal subjects are 900 +/- 3 ms, 1337 +/- 8 ms and 2180 +/- 25 ms in white matter (WM), gray matter (GM) and cerebral spinal fluid (CSF) using the variable flip angle method with FA correction at 3 T, respectively. These results are consistent with previously reported values obtained with much longer acquisition times. The method reduces the total scan time for whole brain T(1) mapping, including FA measurement and calibration, to approximately 6 min. The novelty of this method lies in the in vivo calibration and the correction of the FAs, thereby allowing a rapid and accurate T(1) mapping at high field for many applications.

Adult↗

PubMed2006

Mutations of phosphorylation sites Ser10 and Thr187 of p27Kip1 abolish cytoplasmic redistribution but do not abrogate G0/1 phase arrest in the HepG2 cell line.

The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is an important regulator of cell cycle progression as it negatively regulates G(0/1) progression and plays a major role in controlling the cell cycle. The screening of the p27(Kip1) sequence identified many potential phosphorylation sites. Although Ser(10) and Thr(187) were shown to be important for p27(Kip1) function, the effects of a combined deletion of both sites on p27(Kip1) function are still unknown. To investigate the effects of the overexpression of exogenous p27(Kip1) protein lacking both the Ser(10) and Thr(187) sites on subcellular localization, cell cycle, and proliferation, a plasmid was constructed containing mutations of p27(Kip1) at Ser(10) and Thr(187) (S10A/T187A p27), and transfected into the HepG(2) cell line with Lipofectamine. Wild-type and mutant p27 plasmids S10A and T187A were transfected separately as control groups. As a result, the proliferation of HepG(2) cells was greatly inhibited and cell cycle was arrested in G(0/1) phase after exogenous p27(Kip1) double-mutant expression. All recombinant p27(Kip1) constructs were distributed in the nucleus after synchronization in G(0) phase by treatment with leptomycin B. The expressed wild-type and T187A p27(Kip1) proteins were translocated from the nucleus into cytoplasm when cells were exposed to 20% serum for 8 h, whereas the S10A p27(Kip1) and S10A/T187A p27(Kip1) proteins remained in the nucleus. FACS profiles and cell growth curves indicated that the Ser(10) and Thr(187) double mutant has no significant effect on the biological activities of cell cycle control and growth inhibition. Our results suggest that expression of the p27(Kip1) double-mutant abolishes its cytoplasmic redistribution but does not abrogate G(0/1) phase arrest in the HepG(2) cell line.

Carcinoma, Hepatocellular↗

PubMed2006

Manipulation of image intensity distribution at 7.0 T: passive RF shimming and focusing with dielectric materials.

PURPOSE: To investigate the effects of high dielectric material padding on RF field distribution in the human head at 7.0 T, and demonstrate the feasibility and effectiveness of RF passive shimming and focusing with such an approach. MATERIALS AND METHODS: The intensity distribution changes of gradient-recalled-echo (GRE) and spin-echo (SE) images of a human head acquired with water pads (dielectric constant = 78) placed in specified configurations around the head at 7.0 T were evaluated and compared with computer simulation results using the finite difference time domain (FDTD) method. The contributions to the B(1) field distribution change from the displacement current and conductive current of a given configuration of dielectric padding were determined with computer simulations. RESULTS: MR image intensity distribution in the human head with an RF coil at 7.0 T can be changed drastically by placing water pads around the head. Computer simulations reveal that the high permittivity of water pads results in a strong displacement current that enhances image intensity in the nearby region and alters the intensity distribution of the entire brain. CONCLUSION: The image intensity distribution in the human head at ultra-high field strengths can be effectively manipulated with high permittivity padding. Utilizing this effect, the B(1) field inside the human head of a given RF coil can be adjusted to reduce the B(1) field inhomogeneity artifact associated with the wave behavior (RF passive shimming) or to locally enhance the signal-to-noise ratio (SNR) in targeted regions of interest (ROIs; RF field focusing).

Brain↗

PubMed2006

Factors influencing flip angle mapping in MRI: RF pulse shape, slice-select gradients, off-resonance excitation, and B0 inhomogeneities.

To understand the various effects that influence actual flip angles, and correct for these effects, it is important to precisely quantify the MRI parameters (such as T1, T2, and perfusion). In this paper actual flip angle maps are calculated using a conventional gradient-echo (GRE) sequence with different radiofrequency (RF) pulse shapes (Gaussian, sinc, and truncated-sinc), slice-selection gradients, off-resonance excitations, and B0 field inhomogeneities. The experimental results demonstrate that RF pulse shapes significantly affect the flip angle distribution and calibration factors. Off-resonance RF excitations, B0 nonuniformities, and slice-selection gradients can lead to degradations in the signal intensities of the images used to map the flip angle, and potentially introduce a bias and increased variance in the measured flip angles.

Algorithms↗

PubMed2005

Morphine induces CD4+ T cell IL-4 expression through an adenylyl cyclase mechanism independent of the protein kinase A pathway.

Impaired host defense mechanisms after major operative procedures and trauma are recognized as important factors in the development of infectious complication. Trauma is associated with impaired cellular immunity and CD4+ T cell Th2 differentiation. We have previously implicated morphine treatment as a possible mechanism for Th2 differentiation after injury. In this investigation we first establish that morphine treatment in vivo results in Th2 differentiation and that this effect is mediated through a naltrexone-sensitive opioid receptor. We investigated the intracellular mechanism by which morphine controls CD4+ T cell differentiation and demonstrate that morphine treatment in vitro 1) increases anti CD3/CD28 Ab-induced CD4+ T cell IL-4 protein synthesis, IL-4 mRNA, and GATA-3 mRNA accumulation through a pertussis toxin-sensitive receptor; 2) results in a dose-dependent increase in anti-CD3/CD28 Ab-induced CD4+ T cell cytoplasmic cAMP concentration; and 3) increases the forskolin-stimulated cytoplasmic cAMP level through a pertussis toxin-sensitive receptor. We also demonstrate that chronic morphine treatment increases anti-CD3/CD28 Ab-induced IL-4 promoter activity and IL-4 immunoprotein expression through a p38 MAPK-dependent, but protein kinase A- and Erk1/Erk2-independent, mechanism.

Adenylyl Cyclases↗

PubMed2005

Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection.

Chronic morphine use impairs host innate immune response and increases susceptibility to bacteria and virus. In this study a novel mouse model of chronic morphine treatment, followed by intranasal inoculation with Streptococcus pneumoniae, was used to investigate microbial events and host innate immune response. Our results show that chronic morphine treatment markedly delayed neutrophil recruitment and increased bacterial burden in the lung, spleen, and blood with a subsequent increase in mortality. In morphine-treated animals, before neutrophil recruitment, a significant decrease in TNF-alpha, IL-1, IL-6, MIP-2, and KC was observed both in bronchoalveolar lavage fluids and in lung tissue. In the early phase of infection, we found that accumulation of galectin-3 in the alveolar space of streptococcus-infected lungs was decreased after morphine treatment. The transcription factor NF-kappaB in lung resident cells was also inhibited after morphine treatment. Taken together, these results suggest that chronic morphine treatment in an S. pneumoniae infection model suppresses NF-kappaB gene transcription in lung resident cells, which, in turn, modulates the transcriptional regulation of MIP-2 and inflammatory cytokines. The decreased synthesis of MIP-2 and inflammatory cytokines coupled with the decreased release of galectin-3 result in reduced migration of neutrophils to the site of infection, thereby increasing susceptibility to S. pneumoniae infection after morphine treatment.

Analgesics, Opioid↗

PubMed2005

Measurement and correction of transmitter and receiver induced nonuniformities in vivo.

Signal intensity nonuniformities in high field MR imaging limit the ability of MRI to provide quantitative information and can negatively impact diagnostic scan quality. In this paper, a simple method is described for correcting these effects based on in vivo measurement of the transmission field B1+ and reception sensitivity maps. These maps can be obtained in vivo with either gradient echo (GE) or spin echo (SE) imaging sequences, but the SE approach exhibits an advantage over the GE approach for correcting images over a range of flip angles. In a uniform phantom, this approach reduced the ratio of the signal SD to its mean from around 30% before correction to approximately 6% for the SE approach and 9% for the GE approach after correction. The application of the SE approach for correcting intensity nonuniformities is demonstrated in vivo with human brain images obtained using a conventional spin echo sequence at 3.0 T. Furthermore, it is also shown that this in vivo B1+ and reception sensitivity mapping can be performed using segmented echo planar imaging sequences providing acquisition times of less than 2 min. Although the correction presented here is demonstrated with a simultaneous transmit and receive volume coil, it can be extended to the case of separate transmission and reception coils, including surface and phase array coils.

Algorithms↗

PubMed2005

In vivo method for correcting transmit/receive nonuniformities with phased array coils.

Phased array coils are finding widespread applications in both the research and the clinical setting. However, intensity nonuniformities with such coils can reduce the potential benefits of these coils, particularly for applications such as tissue segmentation. In this work, a method is described for correcting the nonuniform signal response based on in vivo measures of both the transmission field of body coil and the reception sensitivity of phased array coils, separately. For a uniform phantom, the reception sensitivity can be calculated using both Bloch equations and transmission field maps. For a heterogeneous object such as a brain, a minimal contrast acquisition must be obtained to map the receiver nonuniformities. This transmit field/receiver sensitivity (TFRS) approach is compared with the standard methods of using the body coil to obtain a reference scan and low-pass filtering. The quantitative comparison results shows that the TFRS approach provides superior results in correcting intensity nonuniformities for a uniform phantom. This approach reduces the ratio between signal intensity SD of an image and its mean intensity from approximately 21% before correction to 13% after correction. Results are also shown demonstrating the utility of this approach in vivo with human brain images. The method is general and can be applied with most pulse sequences, any coil combination for transmission and reception, and in any anatomic region.

Algorithms↗

PubMed2004

Temperature and SAR calculations for a human head within volume and surface coils at 64 and 300 MHz.

PURPOSE: To examine relationships between specific energy absorption rate (SAR) and temperature distributions in the human head during radio frequency energy deposition in MRI. MATERIALS AND METHODS: A multi-tissue numerical model of the head was developed that considered thermal conductivity, heat capacity, perfusion, heat of metabolism, electrical properties, and density. Calculations of SAR and the resulting temperature increase were performed for different coils at different frequencies. RESULTS: Because of tissue-dependent perfusion rates and thermal conduction, there is not a good overall spatial correlation between SAR and temperature increase. When a volume coil is driven to induce a head average SAR level of either 3.0 or 3.2 W/kg, it is unlikely that a significant temperature increase in the brain will occur due to its high rate of perfusion, although limits on SAR in any 1 g of tissue in the head may be exceeded. CONCLUSION: Attempts to ensure RF safety in MRI often rely on assumptions about local temperature from local SAR levels. The relationship between local SAR and local temperature is not, however, straightforward. In cases where high SAR levels are required due to pulse sequence demands, calculations of temperature may be preferable to calculations of SAR because of the more direct relationship between temperature and safety.

Equipment Safety↗

PubMed2004

Relationship of apparent myocardial T2 and oxygenation: towards quantification of myocardial oxygen extraction fraction.

PURPOSE: To explore the relationship of myocardial T(2) and oxygenation for the quantification of myocardial oxygen extraction fraction (OEF). MATERIALS AND METHODS: A proposed myocardial T(2)-OEF relationship was evaluated by computer simulation and in nine normal dogs in vivo. The relationship was based on a simplified two-compartment T(2) model. In the dogs, dipyridamole was infused intravenously to increase blood flow and change in myocardial oxygen content. The accuracy of the measurement in myocardial OEF in vivo by magnetic resonance imaging (MRI) was determined by arterial and coronary sinus blood sampling. RESULTS: Global myocardial T(2) increased 16.1% from rest to the peak of dipyridamole-induced vasodilation (44.6 +/- 2.1 msec vs. 51.4 +/- 2.1 msec, P < 0.001). Corresponding OEF measured by arterial and venous (AV) sampling decreased from 0.64 +/- 0.15 at rest to 0.18 +/- 0.08 during the dipyridamole vasodilation, whereas OEF calculated by MRI at the peak effect of dipyridamole was 20 +/- 4%. Global myocardial OEF measured dynamically by MRI showed a strong correlation with OEF measured by blood sampling (correlation coefficient (CC) = 0.83) during pharmacologic vasodilation. CONCLUSION: When combined with vasodilator stress, assessment of OEF may provide a putative measure of myocardial flow reserve, allowing consecutive monitoring of myocardial dose-responses to a variety of interventions and offering a new tool for the detection of coronary artery disease.

Animals↗

PubMed2004

Analysis of sulfur-containing compounds in crude oils by comprehensive two-dimensional gas chromatography with sulfur chemiluminescence detection.

This paper reports an analytical method for separating, identifying, and quantifying sulfur-containing compounds in crude oil fraction (IBP-360 degrees C) samples based on comprehensive two-dimensional gas chromatography coupled with a sulfur chemiluminescence detector. Various sulfur-containing compounds and their groups were analyzed with one direct injection. 3620 peaks were detected including 1722 thiols/thioethers/ disulfides/1-ring thiophenes, 953 benzothiophenes, 704 dibenzothiophenes, and 241 benzonaphthothiophenes. The target sulfur compounds and their groups were identified based on the group separation feature and structured retention of comprehensive two-dimensional gas chromatography as well as standard substances. The quantitative analysis of major sulfur-containing compounds and total sulfur was based on the linear response of the sulfur chemiluminescence detector using the internal standard method. The sulfur contents of target sulfur compounds and their groups in 4 crude oil fractions were also determined. The recoveries for standard sulfur-containing compounds were in the range of 90-102%. The quantitative result of total sulfur in the Oman crude oil fraction sample was compared with those from ASTM D 4294 standard method (total S by X-ray fluorescence spectrometry), the relative deviation (RD%) was 4.2% and the precision of the method satisfactory.

Journal Article↗

PubMed2004

Dynamic estimation of the myocardial oxygen extraction ratio during dipyridamole stress by MRI: a preliminary study in canines.

The myocardial oxygen extraction fraction (OEF) reflects the balance between myocardial oxygen supply and demand. The feasibility of quantifying myocardial OEF was demonstrated with MRI during pharmacologic vasodilation in dogs. Dipyridamole was infused intravenously to increase blood flow and change in myocardial oxygen content. Arterial and coronary sinus blood sampling was performed during dipyridamole-induced vasodilation to measure the myocardial blood oxygen content. Myocardial T(2) was measured dynamically during the vasodilation, and quantified with a simplified diffusion model as a function of myocardial OEF and blood volume. The results showed a strong correlation (R(2) = 0.89) between myocardial OEF values measured by MRI and those measured by blood sampling. Regional differences in the OEF were demonstrated by direct infusion of dipyridamole into coronary arteries in dogs. Combined with vasodilator stress, dynamic assessments of the OEF may provide a putative measurement of myocardial flow reserve and allow consecutive monitoring of myocardial dose and response.

Animals↗

PubMed2004

Phantom design method for high-field MRI human systems.

A phantom design method suitable for high-field MRI based on the RF field wave characteristics of sample and experimental validations at 7.0 T and 3.0 T are presented. The RF field distribution in a phantom with a given RF coil system is primarily determined by the sample size relative to the wavelength inside the sample, and the ratio between the displacement and conduction currents. Experimental results demonstrate that the MR image intensity patterns associated with wave behavior in human samples at a given field strength can be reproduced with a phantom at the same or different field strengths once the dimension and penetration constant are scaled by the corresponding wavelength in the sample medium.

Brain Mapping↗

PubMed2004

Chronic morphine treatment differentiates T helper cells to Th2 effector cells by modulating transcription factors GATA 3 and T-bet.

Chronic morphine treatment in animal models has been shown to alter a number of immune parameters including suppression of cellular immunity. T helper cell differentiation into Th2 effector cell may be a major contributing factor to impaired cellular immunity following chronic drug abuse. We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma (Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner. In addition in this paper, we show that chronic morphine treatment resulted in a decrease in IFNgamma and IL-2 mRNA and an increase in IL-4 and IL-5 mRNA accumulation in murine splenocytes. Furthermore, chronic morphine treatment inhibited IFNgamma promoter activity and increased IL-4 promoter activity in respective promoter transfected primary T cells. In addition, we also demonstrate that chronic morphine treatment resulted in an increase in GATA 3 binding to DNA consensus elements in electromobility shift assays and an increase in GATA 3 protein and mRNA levels. In contrast, chronic morphine treatment resulted in a decrease in T-bet mRNA levels. From these data, we conclude that chronic morphine treatment differentiates T helper cell to Th2 effector cells by modulating key master switches that results in committing T helper cell to a Th2 phenotype.

Animals↗

PubMed2004

[Distribution of sulfur-containing compounds in the gasoline range petroleum products].

A capillary gas chromatography coupled with sulfur chemiluminescence detection (GC-SCD) method has been developed for detailed analysis and group-type characterization of sulfur compounds in gasoline range petroleum products. Chemical treatment of the samples was carried out using selective reactions for group-type classification of compounds. A total of 107 sulfur compounds were tentatively classified and identified based on standard substances and retention rule. The relative standard deviations (RSDs) of retention times were no more than 0.25%. The quantitative analysis on major sulfur compounds and total sulfur was carried out based on the linear response of sulfur chemiluminescence detector and the internal standard method. The recoveries were in the range of 96% - 115%. For the sulfur-containing compounds whose concentration exceeded 7 mg/kg, the RSDs of the determination were less than 8.9%. Various types of gasoline were analyzed and their sulfur distributions were investigated using the developed method. The results show that the method can be used to separate, identify and quantitate sulfur-containing compounds.

Chromatography, Gas↗

PubMed2003

Determination of sulfur-containing compounds in diesel oils by comprehensive two-dimensional gas chromatography with a sulfur chemiluminescence detector.

This article reports an analytical method for separating, identifying and quantitating sulfur-containing compounds and their groups in diesel oils (170-400 degrees C) using comprehensive two-dimensional gas chromatography coupled with a sulfur chemiluminescence detector. The identification of target compounds and their groups was based on standard substances, the group separation feature and tile-effect of comprehensive two-dimensional gas chromatography. The quantitative analysis on major sulfur compounds and total sulfur was carried out based on the linear response of sulfur chemiluminescence detector and the internal standards method. The results of total sulfur determination in the samples were compared with those from ASTM D 4294 standard method, the R.S.D. percentage were <6.02%, correctness of this method can meet the industrial requirement. To the end, the method developed was used to investigate the sulfur-containing compounds in different diesel oils, the result shows that the distribution of sulfur-containing compounds in diesel oils from different process units are apparently different. The sulfur compounds in fluid catalytic cracking (FCC), residuum fluid catalytic cracking (RFCC) diesel oils mainly exist in the form of alkyl-substituted dibenzothiophenes that add up to about 40-50% of the total sulfur, while this number is only 6-8 and 20-28% in visbreaking (VB) and delayed-coking (DC) diesel oils, respectively.

Chromatography, Gas↗

PubMed2003

Morphine negatively regulates interferon-gamma promoter activity in activated murine T cells through two distinct cyclic AMP-dependent pathways.

To explore the mechanism by which morphine promotes the incidence of HIV infection, we evaluated the regulatory role of morphine on the interferon-gamma (IFN-gamma) promoter in activated T cells from wild type and mu-opioid receptor knockout mice. Our results show that morphine inhibited anti-CD3/CD28-stimulated IFN-gamma promoter activity in a dose-dependent manner. Chronic morphine treatment of T cells increased intracellular cAMP. To evaluate the role of cAMP in morphine's modulatory function, the effects of dibutyryl cyclic AMP and forskolin were investigated. Both dibutyryl cyclic AMP and forskolin treatment inhibited IFN-gamma promoter activity. Treatment with pertussis toxin, but not with a protein kinase A inhibitor, antagonized morphine's inhibitory effects. Morphine inhibited phosphorylation of ERK1/2 and p38 MAPK; in addition, morphine treatment in the presence of either ERK1/2 or p38 MAPK inhibitor (PD98059 or SB203580) resulted in an additive inhibition of IFN-gamma promoter activity. The transcription factor activator protein-1, NF-kappaB, and nuclear factor of activated T cells (NFAT) were negatively regulated by morphine. Overexpression of NF-kappaB p65 rescued the inhibitory effect of morphine on IFN-gamma promoter activity. However, only when NFATc1 was co-overexpressed with c-fos was the inhibitory effect of morphine on IFN-gamma promoter counteracted. The inhibitory effects of morphine were not observed in T cells obtained from mu-opioid receptor knockout mice, suggesting that morphine modulation of IFN-gamma promoter activity is mediated through the mu-opioid receptor. In summary, our data indicate that morphine modulation of IFN-gamma promoter activity is mediated through two distinct cAMP-dependent pathways, the NF-kappaB signaling pathway and the ERK1/2, p38 MAPK, AP-1/NFAT pathway.

Animals↗