Biomedical subjects

Yi Wang

Publications and source records attributed to Yi Wang.

At least 127 records · Page 7Linked to original sources

PubMed2005

Effects of adrenomedullin gene overexpression on biological behavior of hepatic stellate cells.

AIM: To investigate the effects of adrenomedullin (AM) gene overexpression on the biological characteristics of human hepatic stellate cells (hHSCs) by stable transfection. METHODS: hHSCs which express low basal levels of AM were stably transfected with an expression construct containing rat AM gene or with an empty expression vector. Expression of AM in hHSCs was determined by reverse transcription (RT)-polymerase chain reaction (PCR) and radioimmunoassay (RIA). Cell proliferation was evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and immunocytochemistry. RT-PCR and Western blot were used to test the expression of procollagen types I and III. Protein expressions of interstitial collagenase (MMP-1), gelatinase (MMP-2) and tissue inhibitors of matrix metalloproteinases-2 (TIMP-2) were assessed by Western blot. RESULTS: Two cell clones (A-2, A-8) transfected with the AM gene expressed higher levels of AM mRNA (non-transfected group: 0.86+/-0.11, empty vector group: 1.01+/-0.11, A-2 clone group: 1.44+/-0.08 and A-8 clone group: 1.36+/-0.05) and protein (12.31+/-0.17, 12.35+/-0.12, 12.56+/-0.06 and 12.62+/-0.07) (P<0.05). AM gene overexpression had inhibitory effects on cell proliferation of hHSCs (29.6%, 30.9%, 18.9% and 21.8%, respectively. P<0.05) and expression of procollagen type I (0.58+/-0.1, 0.48+/-0.11, 0.3+/-0.06 and 0.31+/-0.07 at mRNA level) (0.27+/-0.07, 0.3+/-0.06, 0.14+/-0.05 and 0.13+/-0.05 at protein level) (P<0.05) and procollagen type III (0.17+/-0.04, 0.15+/-0.03, 0.1+/-0.02 and 0.09+/-0.02 at mRNA level) (0.22+/-0.04, 0.2+/-0.03, 0.11+/-0.04 and 0.13+/-0.03 at protein level) (P<0.05). Compared with cells non-transfected (TIMP2: 2.77+/-0.03, MMP-2: 0.5+/-0.04, MMP-1: 0.49+/-0.07) and transfected with empty vector (TIMP2: 2.79+/-0.04, MMP-2: 0.48+/-0.03, MMP-1: 0.45+/-0.09), these two clones had lower expression levels of TIMP2(A-2 clone group: 2.7+/-0.02 and A-8 clone group: 2.71+/-0.02) (P<0.05) and MMP-2(A-2 clone group: 0.15+/-0.05 and A-8 clone group: 0.13+/-0.04) (P<0.05) but displayed a higher expression level of MMP-1(A-2 clone group: 0.68+/-0.06 and A-8 clone group: 0.81+/-0.09) (P<0.05). CONCLUSION: AM gene exerts negative influence to some extent on hHSCs by inhibiting proliferation and production of extracellular matrix (ECM) in addition to inducing MMP-1 expression.

Adrenomedullin↗

PubMed2005

Systematic investigation of the signal properties of polycrystalline HgI2 detectors under mammographic, radiographic, fluoroscopic and radiotherapy irradiation conditions.

The signal properties of polycrystalline mercuric iodide (HgI2) film detectors, under irradiation conditions relevant to mammographic, radiographic, fluoroscopic and radiotherapy x-ray imaging, are reported. Each film detector consists of an approximately 230 to approximately 460 microm thick layer of HgI2 (fabricated through physical vapour deposition or a screen-print process) and a thin barrier layer, sandwiched between a pair of opposing electrode plates. The high atomic number, high density and low effective ionization energy, W(EFF), of HgI2 make it an attractive candidate for significantly improving the performance of active matrix, flat-panel imagers (AMFPIs) for several x-ray imaging applications. The temporal behaviour of current from the film detectors in the presence and in the absence of radiation was used to examine dark current levels, the lag and reciprocity of the signal response, x-ray sensitivity and W(EFF). The results are discussed in the context of present AMFPI performance. This study provides performance data for a wide range of potential medical x-ray imaging applications from a single set of detectors and represents the first investigation of the signal properties of polycrystalline mercuric iodide for the radiotherapy application.

Crystallization↗

PubMed2005

Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response.

The role of complement component C5 in asthma remains controversial. Here we examined the contribution of C5 at 3 critical checkpoints during the course of disease. Using an mAb specific for C5, we were able to evaluate the contribution of C5 during (a) the initiation of airway inflammation, (b) the maintenance of airway hyperresponsiveness (AHR), and (c) sustainment of an ongoing airway response to allergen provocation. Our results indicate that C5 is probably activated intrapulmonarily after infections or exposures to allergen and C5 inhibition has profound effects at all 3 critical checkpoints. In contrast to an earlier report, C5-deficient mice with established airway inflammation did not have elevated AHR to nonspecific stimuli. In the presence of airway inflammation, C5a serves as a direct link between the innate immune system and the development of AHR by engaging directly with its receptors expressed in airways. Through their powerful chemotactic and cell activation properties, both C5a and C5b-9 regulate the downstream inflammatory cascade, which results in a massive migration of inflammatory cells into the bronchial airway lumen and triggers the release of multiple harmful inflammatory mediators. This study suggests that targeting C5 is a potential clinical approach for treating patients with asthma.

Animals↗

PubMed2005

Fluvastatin prevents renal injury and expression of lactin-like oxidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia.

BACKGROUND: Lipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery. METHODS: Twenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin [10 mg.kg(-1).d(-1)]. After 16 weeks, serum total cholesterol (TC), low-density lipoprotein (LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using (99m)Tc-DTPA single photon emission computed tomograph ((99m)Tc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry. RESULTS: High cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits. CONCLUSIONS: Fluvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries.

Animals↗

PubMed2005

A family of K+ channel ancillary subunits regulate taste sensitivity in Caenorhabditis elegans.

We have identified a family of ancillary subunits of K(+) channels in Caenorhabditis elegans. MPS-1 and its related members MPS-2, MPS-3, and MPS-4 are detected in the nervous system of the nematode. Electrophysiological analysis in ASE neurons and mammalian cells and epigenetic inactivation by double-stranded RNA interference (RNAi) in vivo show that each MPS can associate with and functionally endow the voltage-gated K(+) channel KVS-1. In the chemosensory neuron ADF, three different MPS subunits combine with KVS-1 to form both binary (MPS-1.KVS-1) and ternary (MPS-2.MPS-3.KVS-1) complexes. RNAi of mps-2, mps-3, or both, enhance the taste of the animal for sodium without altering the susceptibility to other attractants. When sodium is introduced in the test plate as background or as antagonist attractant, the nematode loses the ability to recognize a second attractant. Thus, it appears that the chemosensory apparatus of C. elegans uses sensory thresholds and that a voltage-gated K(+) channel is specifically required for this mechanism.

Amino Acid Sequence↗

PubMed2005

Myocardial first-pass perfusion assessment using rotational long-axis MRI.

PURPOSE: To study a first-pass myocardial perfusion imaging method, such that long-axis imaging slices are obtained rotationally around the short-axis centroid of the left ventricular cavity, in order to improve myocardial coverage and better delineate the basal and apical myocardium. MATERIALS AND METHODS: This rotational long-axis (RLA) method was examined in 12 volunteers and compared to the perfusion images from conventional parallel short-axis (PSA) acquisitions in terms of the contrast to noise ratio (CNR), relative signal upslope and myocardial coverage. Both RLA and PSA first-pass perfusion images were acquired on each volunteer with otherwise identical imaging parameters using the partial Fourier saturation recovery steady state gradient echo sequence with refocused magnetization (TrueFISP) technique. RESULTS: Compared to PSA, RLA perfusion images with identical imaging parameters on the same subject exhibit an average of near 30% improvement in total myocardial area imaged. In addition, true basal and apical myocardium was seen on RLA, but not on PSA. The mean CNR and relative upslope were similar between the two techniques. CONCLUSIONS: This RLA perfusion imaging scheme is superior to the conventional PSA approach in terms of extent myocardial coverage and delineation of basal and apical regions of the left ventricle.

Aged↗

PubMed2005

Myocardial first pass perfusion: steady-state free precession versus spoiled gradient echo and segmented echo planar imaging.

The imaging sequences used in first pass (FP) perfusion to date have important limitations in contrast-to-noise ratio (CNR), temporal and spatial resolution, and myocardial coverage. As a result, controversy exists about optimal imaging strategies for FP myocardial perfusion. Since imaging performance varies from subject to subject, it is difficult to form conclusions without direct comparison of different sequences in the same subject. The purpose of this study was to directly compare the saturation recovery SSFP technique to other more commonly used myocardial first pass perfusion techniques, namely spoiled GRE and segmented EPI. Differences in signal-to-noise ratio (SNR), CNR, relative maximal upslope (RMU) of signal amplitude, and artifacts at comparable temporal and spatial resolution among the three sequences were investigated in computer simulation, contrast agent doped phantoms, and 16 volunteers. The results demonstrate that SSFP perfusion images exhibit an improvement of approximately 77% in SNR and 23% in CNR over spoiled GRE and 85% SNR and 50% CNR over segmented EPI. Mean RMU was similar between SSFP and spoiled GRE, but there was a 58% increase in RMU with SSFP versus segmented EPI.

Adult↗

PubMed2005

Antibacterial constituents from fruit bodies of ascomyce Bulgaria inquinans.

Two ergosterins and two triterpenoids were isolated from the dried fruit bodies of Ascomyce Bulgaria inquinans. By means of chemical (hydrolysis) and spectroscopic methods (NMR, El-MS), their structures were established as betuinic acid (1), cerevisterol (2), (24R)ergosta-7, 22E-diene-3beta, 5alpha, 6beta-triol-3-O-palmitate (3) and ursolic acid (4). Compound 3 is a new compound.

Anti-Bacterial Agents↗

PubMed2005

Antiinflammatory constituents from the roots of Smilax bockii warb.

From 70% ethanol extract of the roots of Smilax bockii warb., seven flavonoids, kaempferol (1), kaempferol-7-O-beta-D-glucopyranoside (2), quercetin (3), isorhamnetin (4), (+)-dihydro-kaempferol (5), engeletin (6), isoengeletin (7), and n-butyl-beta-D-fructopyranoside (8), caffeic acid n-butyl ester (9) were isolated and identified by means of chemical and spectroscopic. Compounds 2, 4, and 6-9 were isolated for the first time from the roots of S. bockii and compounds 2, 8, and 9 were firstly isolated from the genus Smilax. In addition, using the SEAP (Secreted alkaline phosphatase) assay system, we investigated the in vitro anti-inflammatory activity of the 70% ethanol extract of the roots of S. bockii, which showed moderate activity in inhibiting TNF-alpha-induced NF-kappaB activation with an IC50 value of 166.6 microg/mL.

Animals↗

PubMed2005

Iodination and radiolabeling of alpha-allocryptopine with iodine-125.

A procedure for labeling of alpha-allocryptopine with 125I is reported in this article. Alpha-allocryptopine is first iodinated with largely excessive iodine monochloride, and then radiolabeled by isotopic exchange with Na125I in a dichloromethane-water two-phase system. The radiochemical purity and yield of the labeled product are typically as high as 94% and 72%, respectively. Further chromatographic purification gives a highly pure product (radiochemical purity > 99%). The distribution of 125I-labeled alpha-allocryptopine in mice at 2 h after injection shows that the uptake of radioiodine in thyroid is negligibly low.

Animals↗

PubMed2005

Impaired recognition by Toll-like receptor 4 is responsible for exacerbated murine Pneumocystis pneumonia.

We investigated the effect of Toll-like receptor 4 (TLR4) on the progression of murine Pneumocystis pneumonia. TLR4-mutant C3H/HeJ and wild-type C3H/HeN mice were infected with Pneumocystis after depletion of CD4 T cells. Mutant mice lost body weight more quickly and showed exacerbated pulmonary injury even though there was no difference in Pneumocystis organism burden in the lung. Mutant mice showed reduced levels of IL-10, IL-12p40 and MIP-2 accompanied by elevated levels of TNF-alpha and IL-6 in the bronchoalveolar lavage fluid compared with those of wild-type mice 8 weeks after the infection. In response to stimulation with Pneumocystis antigen, the production of IL-10, IL-12p40 and MIP-2 by alveolar macrophages was partially impaired in mutant mice, while that in wild-type mice was suppressed by the anti-TLR4/MD-2 mAb, MTS510. Unlike the response to lipopolysaccharide stimulation, TLR4-reconstituted HEK293 cells showed no elevated NF-kappaB activation after stimulation with Pneumocystis antigen. Taken together, these findings suggest that recognition of Pneumocystis by TLR4 helps to regulate the host inflammatory responses through cytokine and chemokine production by alveolar macrophages.

Animals↗

PubMed2005

Molecular dynamics simulations of proteins in lipid bilayers.

With recent advances in X-ray crystallography of membrane proteins promising many new high-resolution structures, molecular dynamics simulations will become increasingly valuable for understanding membrane protein function, as they can reveal the dynamic behavior concealed in the static structures. Dramatic increases in computational power, in synergy with more efficient computational methodologies, now allow us to carry out molecular dynamics simulations of any structurally known membrane protein in its native environment, covering timescales of up to 0.1 micros. At the frontiers of membrane protein simulations are ion channels, aquaporins, passive and active transporters, and bioenergetic proteins.

Computer Simulation↗

PubMed2005

What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF.

The recent availability of high-resolution structures of two structurally highly homologous, but functionally distinct aquaporins from the same species, namely Escherichia coli AqpZ, a pure water channel, and GlpF, a glycerol channel, presents a unique opportunity to understand the mechanism of substrate selectivity in these channels. Comparison of the free energy profile of glycerol conduction through AqpZ and GlpF reveals a much larger barrier in AqpZ (22.8 kcal/mol) than in GlpF (7.3 kcal/mol). In either channel, the highest barrier is located at the selectivity filter. Analysis of substrate-protein interactions suggests that steric restriction of AqpZ is the main contribution to this large barrier. Another important difference is the presence of a deep energy well at the periplasmic vestibule of GlpF, which was not found in AqpZ. The latter difference can be attributed to the more pronounced structural asymmetry of GlpF, which may play a role in attracting glycerol.

Aquaporins↗

PubMed2005

Elevated plasma levels of vascular endothelial growth factor is associated with marked splenomegaly in chronic myeloid leukemia.

Recent investigations support the idea that angiogenesis is involved in the pathophysiology of hematologic malignancies, including chronic myeloid leukemia (CML). The aim of the present study was to evaluate plasma levels of VEGF and bFGF in a cohort of 51 chronic-phase CML patients at the time of diagnosis, as well as to investigate the effect of imatinib therapy on VEGF amounts in CML patients. Plasma VEGF levels were significantly higher in patients studied as compared with the 20 healthy subjects (p<0.001), the median plasma VEGF level detected in patients analysed and healthy controls was 433.4 pg mL(-1) (range 65.2-2,452.7 pg mL(-1)) and 81.6 pg mL(-1) (range 44.2-338.7 pg mL(-1)), respectively. On the other hand, no difference in bFGF plasma levels could be found between chronic-phase CML patients and the control group. There were significant associations between plasma VEGF levels and some characteristics of patients evaluated, with trends for higher VEGF values in patients with enlarged spleens (p = 0.02) and those with higher platelet count (p<0.001). Of the patients, 11 received imatinib treatment. The initial VEGF levels markedly decreased after 6 months of imatinib therapy in each patient (p<0.001). These data support the important pathophysiological role of VEGF in CML. Further studies aiming to explore the detailed angiogenic profile of CML may help in developing new therapeutic strategies for this myeloproliferative disorder.

Biomarkers↗

PubMed2005

Metamorphopsia after successful retinal detachment surgery: an optical coherence tomography study.

PURPOSE: To investigate the findings in optical coherence tomography (OCT) in eyes with metamorphopsia after scleral buckling surgery for macula-off retinal detachment. METHODS: A total of 46 patients (46 eyes) with macula-off retinal detachment were prospectively studied 2 months after successful scleral buckling surgery. Patients were examined with the Amsler grid, fundus biomicroscopy and OCT. RESULTS: At the 2 month follow-up, 31/46 (67%) patients had metamorphopsia; 24/31 (77%) of these patients had an abnormal macular structure on OCT and 7/31 (23%) showed a normal macula. However, of the 15 patients in the non-metamorphopsia group, 4/15 (27%) had an abnormal macula and 11/15 (73%) had a normal macula (p = 0.0015). The most common finding on OCT was neurosensory retinal detachment. CONCLUSIONS: Metamorphopsia after scleral buckling surgery in macula-off detachment is more common in patients in whom abnormal macular structure is seen on the OCT scan compared to those showing a normal macular structure. Neurosensory retinal detachment is the most common pathology in these patients.

Adolescent↗

PubMed2005

Segmented phosphors: MEMS-based high quantum efficiency detectors for megavoltage x-ray imaging.

Current electronic portal imaging devices (EPIDs) based on active matrix flat panel imager (AMFPI) technology use a metal plate+phosphor screen combination for x-ray conversion. As a result, these devices face a severe trade-off between x-ray quantum efficiency (QE) and spatial resolution, thus, significantly limiting their imaging performance. In this work, we present a novel detector design for indirect detection-based AMFPI EPIDs that aims to circumvent this trade-off. The detectors were developed using micro-electro-mechanical system (MEMS)-based fabrication techniques and consist of a grid of up to approximately 2 mm tall, optically isolated cells of a photoresist material, SU-8. The cells are dimensionally matched to the pixels of the AMFPI array, and packed with a scintillating phosphor. In this paper, various design considerations for such detectors are examined. An empirical evaluation of three small-area (approximately 7 x 7 cm2) prototype detectors is performed in order to study the effects of two design parameters--cell height and phosphor packing density, both of which are important determinants of the imaging performance. Measurements of the x-ray sensitivity, modulation transfer function (MTF) and noise power spectrum (NPS) were performed under radiotherapy conditions (6 MV), and the detective quantum efficiency (DQE) was determined for each prototype SU-8 detector. In addition, theoretical calculations using Monte Carlo simulations were performed to determine the QE of each detector, as well as the inherent spatial resolution due to the spread of absorbed energy. The results of the present studies were compared with corresponding measurements published in an earlier study using a Lanex Fast-B phosphor screen coupled to an indirect detection array of the same design. The SU-8 detectors exhibit up to 3 times higher QE, while achieving spatial resolution comparable or superior to Lanex Fast-B. However, the DQE performance of these early prototypes is significantly lower than expected due to high levels of optical Swank noise. Consequently, the SU-8 detectors presently exhibit DQE values comparable to Lanex Fast-B at zero spatial frequency and significantly lower than Fast-B at higher frequencies. Finally, strategies for reducing Swank noise are discussed and theoretical calculations, based on the cascaded systems model, are presented in order to estimate the performance improvement that can be achieved through such noise reduction.

Computer-Aided Design↗

PubMed2005

Segmented crystalline scintillators: an initial investigation of high quantum efficiency detectors for megavoltage x-ray imaging.

Electronic portal imaging devices (EPIDs) based on indirect detection, active matrix flat panel imagers (AMFPIs) have become the technology of choice for geometric verification of patient localization and dose delivery in external beam radiotherapy. However, current AMFPI EPIDs, which are based on powdered-phosphor screens, make use of only approximately 2% of the incident radiation, thus severely limiting their imaging performance as quantified by the detective quantum efficiency (DQE) (approximately 1%, compared to approximately 75% for kilovoltage AMFPIs). With the rapidly increasing adoption of image-guided techniques in virtually every aspect of radiotherapy, there exist strong incentives to develop high-DQE megavoltage x-ray imagers, capable of providing soft-tissue contrast at very low doses in megavoltage tomographic and, potentially, projection imaging. In this work we present a systematic theoretical and preliminary empirical evaluation of a promising, high-quantum-efficiency, megavoltage x-ray detector design based on a two-dimensional matrix of thick, optically isolated, crystalline scintillator elements. The detector is coupled with an indirect detection-based active matrix array, with the center-to-center spacing of the crystalline elements chosen to match the pitch of the underlying array pixels. Such a design enables the utilization of a significantly larger fraction of the incident radiation (up to 80% for a 6 MV beam), through increases in the thickness of the crystalline elements, without loss of spatial resolution due to the spread of optical photons. Radiation damage studies were performed on test samples of two candidate scintillator materials, CsI(Tl) and BGO, under conditions relevant to radiotherapy imaging. A detailed Monte Carlo-based study was performed in order to examine the signal, spatial spreading, and noise properties of the absorbed energy for several segmented detector configurations. Parameters studied included scintillator material, septal wall material, detector thickness, and the thickness of the septal walls. The results of the Monte Carlo simulations were used to estimate the upper limits of the modulation transfer function, noise power spectrum and the DQE for a select number of configurations. An exploratory, small-area prototype segmented detector was fabricated by infusing crystalline CsI(Tl) in a 2 mm thick tungsten matrix, and the signal response was measured under radiotherapy imaging conditions. Results from the radiation damage studies showed that both CsI(Tl) and BGO exhibited less than approximately 15% reduction in light output after 2500 cGy equivalent dose. The prototype CsI(Tl) segmented detector exhibited high uniformity, but a lower-than-expected magnitude of signal response. Finally, results from Monte Carlo studies strongly indicate that high scintillator-fill-factor configurations, incorporating high-density scintillator and septal wall materials, could achieve up to 50 times higher DQE compared to current AMFPI EPIDs.

Computer Simulation↗

PubMed2005

Multiple sequence alignment using an exhaustive and greedy algorithm.

We describe an exhaustive and greedy algorithm for improving the accuracy of multiple sequence alignment. A simple progressive alignment approach is employed to provide initial alignments. The initial alignment is then iteratively optimized against an objective function. For any working alignment, the optimization involves three operations: insertions, deletions and shuffles of gaps. The optimization is exhaustive since the algorithm applies the above operations to all eligible positions of an alignment. It is also greedy since only the operation that gives the best improving objective score will be accepted. The algorithms have been implemented in the EGMA (Exhaustive and Greedy Multiple Alignment) package using Java programming language, and have been evaluated using the BAliBASE benchmark alignment database. Although EGMA is not guaranteed to produce globally optimized alignment, the tests indicate that EGMA is able to build alignments with high quality consistently, compared with other commonly used iterative and non-iterative alignment programs. It is also useful for refining multiple alignments obtained by other methods.

Algorithms↗