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Biomedical subjects

Q Chen

Publications and source records attributed to Q Chen.

At least 217 records · Page 12Linked to original sources
PubMed2000

The duffy-binding-like domain 1 of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a heparan sulfate ligand that requires 12 mers for binding.

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surfaces of parasitized red blood cells (pRBC), mediates rosetting, a virulent phenotype. Here, we show that pRBC specifically bind heparan sulfate (HS) and heparin onto their surfaces and that the rosetting ligand PfEMP1 specifically adheres to heparin-Sepharose when extracted from the surfaces of radioiodinated infected RBC. An analysis of the binding properties of the different regions of PfEMP1 provides evidence that the Duffy-binding-like domain-1 (DBL-1) is the predominant ligand involved in HS and heparin binding. Soluble DBL-1 requires a minimal heparin fragment size of a 12-mer ( approximately 4 kd) for binding and is critically dependent on N-sulfation. A 12-mer is also the minimal heparin fragment that disrupts naturally formed rosettes. DBL-1 binds specifically to erythrocytes and also to HS from endothelial cells and human aorta but not to chondroitin sulfate A, suggesting that different PfEMP1s mediate adhesion to distinct glycosaminoglycans in individual malaria parasites. Present data suggest that HS on endothelial cells may also be involved in the sequestration of pRBC. Elucidation of these binding mechanisms opens up new possibilities for therapeutic strategies targeting adhesive interactions of pRBC.

Animals↗
PubMed2000

[Effects of black and red rice on the formation of aortic plaques and blood lipids in rabbits].

In order to observe the antiatherosclerotic effects of black and red rice and to find out their mechanism, 24 New Zealand male white rabbits (average body weight 1.91 kg) were divided randomly into three groups (white rice, black rice and red rice groups). The rabbits were fed a cholesterol-enriched diet (cholesterol 5 g/kg, lard 35 g/kg) containing 300 g/kg white, black and red rice powder respectively. The rabbits were sacrificed 10 weeks later. The aorta was dissected and stained in 0.5% oilred-isopropanol solution. The plaque area and total area of aorta were measured by an automatic image analyzer. Serum lipids were determined by an automatic analyzer. The results showed that the plaque area (% of total surface) in the black and red rice groups was significantly lower than that in the white rice group (P < 0.05). Serum TG, TC, LDL-C, ApoB and ApoAI/ApoB were not significantly different among the three groups (P > 0.05). However, the concentrations of HDL-C and ApoAI were significantly higher in the black and red rice groups than those in the white groups (P < 0.05). No significant difference was found between the black and red rice groups. It is concluded that black and red rice might be effective in reducing atherosclerotic plaques on the aorta of rabbits fed a cholesterol-enriched diet. The effectiveness of black and red rice against atherosclerosis might be related to the high level of serum HDL-C and ApoAI.

Animals↗
PubMed2000

Suppression of CYP2C11 gene transcription by interleukin-1 mediated by NF-kappaB binding at the transcription start site.

Inflammatory cytokines cause the down-regulation of multiple cytochrome P450 mRNAs, but the transcriptional mechanisms involved are not known. We investigated the role of a putative negative NF-kappaB-responsive element, nkappaB-RE1, in the down-regulation of the CYP2C11 gene in rat hepatocytes. This sequence spans the transcription start site of CYP2C11, from positions -2 to +8. Electrophoretic mobility shift assays showed that nuclear extracts from livers of rats treated with bacterial lipopolysaccharide, or from hepatocytes treated with interleukin-1beta, formed a protein complex with an oligonucleotide probe containing the nkappaB-RE1, and that this complex contained predominantly the p50 subunit of NF-kappaB. Binding of NF-kappaB to the nkappaB-RE1 probe was of lower affinity than to a probe containing the prototypic NF-kappaB enhancer of the immunoglobulin kappa chain gene. Mutations in the 5'-end of the nkappaB-RE1, and to a lesser extent the 3'-end, reduced the affinity of NF-kappaB for this element. Introduction of the 5'-mutation into nkappaB-RE1 abolished the response of the -200-CYP2C11-chloramphenicol acetyltransferase reporter construct to interleukin-1 or lipopolysaccharide. We conclude that nkappaB-RE1 is a functional negative regulatory element that participates in the inflammatory suppression of CYP2C11.

Animals↗
PubMed2000

Mechanoregulation of chondrocyte proliferation, maturation, and hypertrophy: ion-channel dependent transduction of matrix deformation signals.

Mechanical stress-induced matrix deformation plays a fundamental role in regulating cellular activities; however, little is known about its underlying mechanisms. To understand the effects of matrix deformation on chondrocytes, we characterized primary chondrocytes cultured on three-dimensional collagen scaffoldings, which can be loaded mechanically with a computer-controlled "Bio-Stretch" device. Cyclic matrix deformation greatly stimulated proliferation of immature chondrocytes, but not that of hypertrophic chondrocytes. This indicates that mechanical stimulation of chondrocyte proliferation is developmental stage specific. Synthesis of cartilage matrix protein (CMP/matrilin-1), a mature chondrocyte marker, and type X collagen, a hypertrophic chondrocyte marker, was up-regulated by stretch-induced matrix deformation. Therefore, genes of CMP and type X collagen are responsive to mechanical stress. Mechanical stimulation of the mRNA levels of CMP and type X collagen occurred exactly at the same time points when these markers were synthesized by nonloading cells. This indicates that cyclic matrix deformation does not alter the speed of differentiation, but affects the extent of differentiation. The addition of the stretch-activated channel blocker gadolinium during loading abolished mechanical stimulation of chondrocyte proliferation, but did not affect the up-regulation of CMP mRNA by mechanical stretch. In contrast, the calcium channel blocker nifedipine inhibited both the stretch-induced proliferation and the increase of CMP mRNA. This suggests that stretch-induced matrix deformation regulates chondrocyte proliferation and differentiation via two signal transduction pathways, with stretch-activated channels involved in transducing the proliferative signals and calcium channels involved in transducing the signals for both proliferation and differentiation.

Animals↗
PubMed2000

Transcriptional activation of the hepatocyte growth factor receptor (c-met) gene by its ligand (hepatocyte growth factor) is mediated through AP-1.

Hepatocyte Growth Factor (HGF) exerts its biological effects via binding and activating a transmembrane protein tyrosine kinase receptor known as c-Met. Previous studies from our laboratory demonstrated that c-met gene expression is inducible by its own ligand (HGF). However, the molecular mechanism(s) involved in this process are unknown. The present study was carried out to address this question. Transfection of various c-met-CAT promoter constructs into the mouse hepatocellular carcinoma cell line Hepa 1-6 in combination with electrophoretic mobility shift assays (EMSA) identified the responsive element as an activated protein-1 (AP-1) binding site (TGAGTCA) within the c-met core promoter region at position -158 to -152. The c-met AP-1 element binds specifically to AP-1 protein as verified by supershift assays. EMSA studies and mutational analyses of the promoter region also revealed that the members of the Sp family of transcription factors (Sp-1 and Sp-3) bind to the c-met Sp-1 element (located at position -124) which is adjacent to the AP-1 site. We show that Sp binding dampens binding of AP-1 to its cognate site in the c-met promoter region. Stimulation of Hepa 1-6 cells with HGF resulted in a rapid and dramatic enhancement of the AP-1 binding activity as well as an overall increase in the level of AP-1 protein. Cotransfection of AP-1 expression vectors (c-Fos plus c-Jun) with c-met promoter constructs resulted in stimulation of c-met promoter activity. We found that transactivation of the c-met promoter by AP-1 can be blocked by Curcumin, an inhibitor of AP-1. Moreover, we found that the induction of the endogenous c-met gene by HGF is inhibited by the addition of Curcumin. The results demonstrate that the HGF-induced transcription of the c-met gene by HGF is, at least in part, due to activation of the AP-1 pathway.

5' Untranslated Regions↗
PubMed2000

Astrocytes express specific variants of CaM KII delta and gamma, but not alpha and beta, that determine their cellular localizations.

Multiple isoforms of type II Ca(2+)-calmodulin-dependent kinase (CaM KII) are composed of two major neuron-specific subunits, designated alpha and beta, and two less well-characterized subunits that are also expressed in non-neuronal tissues, designated delta and gamma. Regulated expression of these 4 gene products, and several variants produced by alternative splicing, shows temporal and regional specificity and influences intracellular targeting. We used immunoblotting and RT-PCR to analyze subunit and variant expression and distribution in cultured cerebellar astrocytes and neurons, and whole cerebellar cortex from rodent brain. The data indicate that: (i) astrocytes express a single splice variant of delta, namely delta(2); (ii) like neurons, astrocytes express two forms of CaM KII gamma; gamma(B) and gamma(A); (iii) these CaM KII variants are enriched in the supernate fraction in astrocytes, and the particulate fraction in neurons; (iv) unlike neurons, astrocytes do not express detectable levels of alpha or beta subunits or their respective splice variants. The results indicate that neurons and astrocytes express distinct CaM KII subunits and variants that localize to distinct subcellular compartments and, by inference, exert distinct cellular functions.

Animals↗
PubMed2000

Effect of respiratory phases on MR lung signal intensity and lung conspicuity using segmented multiple inversion recovery turbo spin echo (MIR-TSE).

The purpose of this study was to determine the effect of respiratory phase on signal intensity of the lung. Lung images were obtained from eleven healthy human volunteers using a multiple inversion recovery segmented turbo spin echo sequence (MIR-TSE). MIR exploits the difference in T(1) between different tissues to effectively null signal contributions from fat and muscle for improved visualization of the lung. The volunteers were asked to perform breath-holding on end inspiration or end expiration. There was a significant decrease in signal intensity of the lung with average SNR of 7.3 +/- 0.9 vs. 14.4 +/- 0.8 for coronal slices, and 9.5 +/-1.5 vs. 16.0 +/-2.4 for sagittal breath-hold images acquired during end inspiration compared with end expiration. It is concluded that MRI of the lungs should be performed during end expiration in order to optimize image quality.

Female↗
PubMed2000

1H magnetic resonance imaging of human lung using inversion recovery turbo spin echo.

Evaluation of lung pathologies using magnetic resonance imaging remains limited, primarily due to the lung's low proton density and high density of magnetic field susceptibility gradients. It is hypothesized that visualization of the lung is possible if signal intensity from muscle and/or fat is suppressed or reduced. Using the inversion recovery and frequency selective saturation pulse with a half-Fourier single-shot turbo spin-echo (HASTE) or a segmented, centric reordered turbo spin-echo (TSE) readout, signal intensity and contrast of tissues can be manipulated to enhance the visibility of the lung. Multislice images of the lung from 10 healthy volunteers were acquired with negligible motion artifacts. Peripheral pulmonary vessels appear well delineated. T(1) maps of the lung are also presented; the overall average was 1335 +/- 85 msec and 1245 +/- 93 msec with the volunteers performing breath-holding on end-expiration and end-inspiration, respectively. This difference is statistically significant, at P < 0.01.

Adult↗
PubMed2000

Semiquantitative assessment of uterine perfusion using first pass dynamic contrast-enhanced MR imaging for patients treated with uterine fibroid embolization.

The feasibility of using first pass dynamic contrast-enhanced MRI to monitor semiquantitatively the perfusion changes of the uterus after uterine arterial embolization is demonstrated. Ten women, who underwent uterine arterial embolization for fibroid treatment, were included in this study. To derive a perfusion index, an additional axial slice through the abdominal aorta was obtained simultaneously when acquiring MR perfusion data. This technique may prove valuable in monitoring the outcome of uterine arterial embolization and documentation of preserved uterine perfusion after this procedure. J. Magn. Reson. Imaging 2000;12:1004-1008.

Adult↗
PubMed2000

Imaging pulmonary blood flow and perfusion using phase-sensitive selective inversion recovery.

A technique is described for imaging pulmonary blood flow using a phase-sensitive selective inversion recovery (PS-SIR) sequence. PS-SIR image reconstruction provides excellent contrast, differentiating fully relaxed inflowing blood from inverted blood and lung tissue. The magnetization of the inverted tissues remains negative at any inversion delay less than that at which the magnetization of the lung tissue is nulled, whereas that of the fully relaxed inflowing blood is always positive. Pulmonary blood flow can be observed by tracking the propagation of the pixels with positive values. Five healthy volunteers were imaged. The normal pattern of blood flow advancing from the central arteries toward the peripheries and into the lung parenchyma with return toward the center via draining veins was depicted. The method offers promise for evaluating pulmonary blood flow without the need for image subtraction or contrast administration. Magn Reson Med 43:793-795, 2000.

Adult↗
PubMed2000

Multiple inversion recovery MR subtraction imaging of human ventilation from inhalation of room air and pure oxygen.

The feasibility of MR subtraction imaging of lung ventilation using air against oxygen using a multiple inversion recovery half-Fourier single-shot turbo spin echo (MIR-HASTE) sequence was investigated. Eight healthy, nonsmoking volunteers (3 males, 5 females; from 27 to 48 years of age) were studied on a 1.5 T MR unit. The ventilation image was obtained from the subtraction of the images acquired with the subject inhaling room air and 100% oxygen. By suppressing the signal from subcutaneous fat and thoracic muscle, MIR-HASTE improved the subtraction of signal arising from background tissues. Lung parenchyma, pulmonary veins, descending aorta, spleen, and kidney showed high signal difference, but pulmonary arteries exhibited minimal signal difference. Because of minimal signal change in the pulmonary arteries after inhalation of 100% oxygen, the average signal decreases in the left and right lungs including hilus and periphery amounted to only 19.4+/-4.5 and 20.2+/-3.4%, respectively, compared with regional averages of 23.6+/-5.4 and 24.1+/-3.1% for both lung peripheries alone. Magn Reson Med 43:913-916, 2000.

Administration, Inhalation↗
PubMed2000

Noninvasive pulmonary perfusion imaging by STAR-HASTE sequence.

The STAR-HASTE sequence has been shown to be useful for perfusion imaging in areas that are plagued by magnetic susceptibility artifacts. Pulmonary perfusion imaging with this technique was attempted in this study. Quantitative analysis was also conducted, using an appropriate kinetic model in one subject. In six healthy subjects, gradual enhancement was observed in pulmonary artery to distal lung parenchyma when inflow time was increased. Our initial results suggest that noninvasive evaluation of pulmonary perfusion by magnetic resonance imaging without administration of an exogenous agent is possible.

Adult↗
PubMed2000

SPACR in the interphotoreceptor matrix of the mouse retina: molecular, biochemical and immunohistochemical characterization.

Mouse SPACR cDNA was cloned by screening a mouse retina cDNA library using a PCR probe derived from human SPACR cDNA. Mouse SPACR cDNA comprises 3675 bp containing an open reading frame coding for 742 amino acids. Multitissue Northern blot analysis and in situ hybridization studies indicate that SPACR expression is restricted to retinal photoreceptors. The SPACR core protein was identified with Western blotting following SDS-PAGE with a SPACR C-terminal peptide polyclonal antibody and a chondroitin-6-sulfate Deltadisaccharide monoclonal antibody. The 150 kD immunopositive band was isolated, digested with trypsin and the peptides analysed by MALDI mass spectroscopy. Peptide mass mapping confirmed the identity of the 150 kD immunopositive band to be mouse SPACR core protein. Alignment comparisons of the deduced amino acid sequence of mouse and human SPACR show 64% homology. Like SPACR in the human interphotoreceptor matrix, the mouse orthologue contains a large central mucin-like domain flanked by consensus sites for N-linked oligosaccharide attachment, one EGF-like domain and four hyaluronan-binding motifs. Unlike human SPACR, which contains no conventional consensus sites for glycosaminoglycan attachment, mouse SPACR contains three. Recent biochemical studies of human and mouse SPACR protein indicate that this novel interphotoreceptor matrix molecule is a glycoprotein in human and a proteoglycan in the mouse. The presence of consensus sites for glycosaminoglycan attachment in the deduced sequence of mouse SPACR and the absence of these sites in human SPACR provide molecular verification of our biochemical results, suggesting that differences in post-translational modifications of SPACR may be important in SPACR function in foveate and non-foveate retinas.

Amino Acid Sequence↗
PubMed2000

Genetic polymorphism of RhD-negative associated haplotypes in the Chinese.

The Rh blood group is the most polymorphic human blood group system, and is clinically significant in transfusion medicine. Individuals are classified as Rh-positive and Rh-negative depending on the presence or absence of the D antigen on the red cell surface. The RhD-negative trait could be generated by multiple genetic mechanisms, which have been shown to be ethnic group-dependent. In this study, we evaluated the status of seven RHD-specific exons (exons 3, 4, 5, 6, 7, 9, and 10) and RH intron 4 in 119 Chinese blood donors, using the sequence-specific primers polymerase chain reaction (SSP-PCR). Of the 87 individuals who were RhD-negative, 52 with the ce/ce, ce/cE, or Ce/ce genotype (60%) lacked the above seven RHD exons; 22 with the Ce/Ce or Ce/ce genotype (25%) had all the RHD exons examined; 13 with the Ce/ce genotype (15%) carried at least one RHD exon. Antigen association analysis suggested the existence of a novel class of RhD-negative associated haplotypes in the Chinese, tentatively denoted D(nf)Ce. The D(nf)Ce haplotype consisted of a normal RHCe allele and a nonfunctional RHD gene, which vary depending on the structure of the RHD gene. Among the RhD-negative Chinese, the estimated frequencies of the dce, dCe, and D(nf)Ce haplotypes were 0.7500, 0.0465, and 0.2035, respectively. No statistically significant deviation from Hardy-Weinberg equilibrium was observed using this genetic model.

China↗
PubMed2000

The questionable role of a microsomal delta8 acyl-coA-dependent desaturase in the biosynthesis of polyunsaturated fatty acids.

Several experimental approaches were used to determine whether rat liver and testes express an acyl-CoA-dependent delta8 desaturase. When [1-14C]5,11,14-eicosatrienoic acid was injected via the tail vein, or directly into testes, it was incorporated into liver and testes phospholipids, but it was not metabolized to other labeled fatty acids. When [1-14C]11,14-eicosadienoic acid was injected, via the tail vein or directly into testes, or incubated with microsomes from both tissues, it was only metabolized to 5,11,14-eicosatrienoic acid. When ethyl 5,5,11,11,14,14-d6-5,11,14-eicosatrienoate was fed to rats maintained on a diet devoid of fat, it primarily replaced esterified 5,8,11-eicosatrienoic acid, but not arachidonic acid. No labeled linoleate or arachidonate were detected. Dietary ethyl linoleate and ethyl 19,19,20,20-d4-1,2-13C-11,14-eicosadienoate were about equally effective as precursors of esterified arachidonate. The doubly labeled 11,14-eicosadienoate was metabolized primarily by conversion to 17,17,18,18-d4-9,12-ocatdecadienoic acid, followed by its conversion to yield esterified arachidonate, with a mass four units greater than endogenous arachidonate. In addition, the doubly labeled substrate gave rise to a small amount of arachidonate, six mass units greater than endogenous arachidonate. No evidence was obtained, with the radiolabeled substrates, for the presence of a delta8 desaturase. However, the presence of an ion, six mass units greater than endogenous arachidonate when doubly labeled 11,14-eicosadienoate was fed, suggests that a small amount of the substrate may have been metabolized by the sequential use of delta8 and delta5 desaturases.

Animals↗
PubMed2000

Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies.

Reactive nitrogen species may play a mechanistic role in neurodegenerative diseases by posttranslationally altering normal brain proteins. In support of this hypothesis, we demonstrate that an anti-3-nitrotyrosine polyclonal antibody stains all of the major hallmark lesions of synucleinopathies including Lewy bodies, Lewy neurites and neuraxonal spheroids in dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and neurodegeneration with brain iron accumulation type 1, as well as glial and neuronal cytoplasmic inclusions in multiple system atrophy. This antibody predominantly recognized nitrated alpha-synuclein when compared to other in vitro nitrated constituents of these pathological lesions, such as neurofilament subunits and microtubules. Collectively, these findings imply that alpha-synuclein is nitrated in pathological lesions. The widespread presence of nitrated alpha-synuclein in diverse intracellular inclusions suggests that oxidation/nitration is involved in the onset and/or progression of neurodegenerative diseases.

Adult↗
PubMed2000

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance imaging is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Humans↗