Biomedical subjects

Ying Liu

Publications and source records attributed to Ying Liu.

At least 271 records · Page 15Linked to original sources

PubMed2004

Electrochemical and bioelectrochemistry properties of room-temperature ionic liquids and carbon composite materials.

Room-temperature ionic liquids (RTILs) are liquids at room temperature and represent a new class of nonaqueous but polar solvents with high ionic conductivity. The conductivity property of carbon nanotubes/RTILs and carbon microbeads/RTILs composite materials has been studied using ac impedance technology. Enzyme coated by RTILs-modified gold and glassy carbon electrodes allow efficient electron transfer between the electrode and the protein and also catalyze the reduction of O2 and H2O2.

Biochemistry↗

PubMed2004

Targeted mutagenesis of the angiogenic protein CCN1 (CYR61). Selective inactivation of integrin alpha6beta1-heparan sulfate proteoglycan coreceptor-mediated cellular functions.

The matricellular protein CCN1 (CYR61) regulates multiple cellular processes and plays essential roles in embryonic vascular development. A ligand of several integrin receptors, CCN1 acts through integrin alpha6beta1 and heparan sulfate proteoglycans (HSPGs) to promote specific functions in fibroblasts, smooth muscle cells, and endothelial cells. We have previously identified a novel alpha6beta1 binding site, T1, in domain III of CCN1. Here we uncover two novel 16-residue sequences, H1 and H2, in domain IV that can support alpha6beta1- and HSPGs-dependent cell adhesion, suggesting that these sequences contain closely juxtaposed or overlapping sites for interaction with alpha6beta1 and HSPGs. Furthermore, fibroblast adhesion to the H1 and H2 peptides is sufficient to induce prolonged MAPK activation, whereas adhesion to T1 induces transient MAPK activation. To dissect the roles of these sites in CCN1 function, we have created mutants disrupted in T1, H1, and H2 or in all three sites in the context of full-length CCN1. We show that the T1 and H1/H2 sites are functionally non-equivalent, and disruption of these sites differentially affected cell adhesion, migration, mitogen-activated protein kinase activation, and regulation of gene expression. Disruption of all three sites completely abolished alpha6beta1-HSPG-mediated cellular activities. All mutants disrupting T1, H1, and H2 fully retain alphavbeta3-mediated pro-angiogenic activities, indicating that these mutants are biologically active and are defective only in alpha6beta1-HSPG-mediated functions. Together, these findings identify and dissect the differential roles of the three sites (T1, H1, H2) required for alpha6beta1-HSPG-dependent CCN1 activities and provide a strategy to investigate these alpha6beta1-HSPG-specific activities in vivo.

Amino Acid Sequence↗

PubMed2004

Recursion equations in predicting band width under gradient elution.

The evolution of solute zone under gradient elution is a typical problem of non-linear continuity equation since the local diffusion coefficient and local migration velocity of the mass cells of solute zones are the functions of position and time due to space- and time-variable mobile phase composition. In this paper, based on the mesoscopic approaches (Lagrangian description, the continuity theory and the local equilibrium assumption), the evolution of solute zones in space- and time-dependent fields is described by the iterative addition of local probability density of the mass cells of solute zones. Furthermore, on macroscopic levels, the recursion equations have been proposed to simulate zone migration and spreading in reversed-phase high-performance liquid chromatography (RP-HPLC) through directly relating local retention factor and local diffusion coefficient to local mobile phase concentration. This new approach differs entirely from the traditional theories on plate concept with Eulerian description, since band width recursion equation is actually the accumulation of local diffusion coefficients of solute zones to discrete-time slices. Recursion equations and literature equations were used in dealing with same experimental data in RP-HPLC, and the comparison results show that the recursion equations can accurately predict band width under gradient elution.

Chromatography, High Pressure Liquid↗

PubMed2004

Association of -238G/A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population.

AIM: To clarify whether -238G/A polymorphism of tumor necrosis factor-alpha (TNF-alpha) gene promoter region was associated with outcomes of hepatitis B virus (HBV) infection in Han population of northern China, and to analyze the gene-environment interaction between -238G/A polymorphism and cigarette smoking or alcohol consumption. METHODS: A case-control study was conducted to analyze the association of TNF-alpha gene promoter polymorphism with HBV infection outcomes. A total of 207 patients with chronic hepatitis B (HB) and 148 cases of self-limited HBV infection from Ditan Hospital and Shunyi District Hospital in Beijing, respectively were recruited. History of smoking and alcohol drinking was inquired by a questionnaire. The -238G/A polymorphism of TNF-alpha gene promoter was genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of GG and GA genotypes were 98.07% and 1.93% in chronic HB patients and 93.24% and 6.76% in self-limited HBV infection individuals, respectively (chi(2)=5.30, P=0.02). The frequency of G allele was significantly higher in patients with chronic HB that in individuals with self-limited HBV infection (99.03% vs 96.62%, chi(2)=5.20, P=0.02). Only modestly increased risk of onset of chronic HB was found in smokers (OR=1.40, 95% CI: 0.87-2.28, P=0.14) and drinkers (OR=1.26, 95%CI: 0.78-2.05, P=0.32). There was a positive interaction between genotype GG and cigarette smoking with an interaction index (II) of 2.95, or alcohol consumption with an II of 1.64. CONCLUSION: The -238G/A polymorphism of TNF-alpha gene promoter region is independently associated with different outcomes of HBV infection.

Asian People↗

PubMed2004

[Fluorodeoxyglucose-positron emission tomography in carcinoma of the esophagogastric junction].

OBJECTIVE: To assess the value of fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) in carcinoma of the esophagogastric junction. METHODS: From December 1998 to April 2002, 27 patients were imaged with FDG-PET and FDG avid masses in the esophagogastric junction were found in every patient. FDG-PET data was analyzed by visual method and standardized uptake value (SUV). FDG-PET results were compared with pathological results and follow-up survey. RESULTS: 16 carcinomas of the esophagogastric junction and 11 non-specific FDG-avid masses of normal stomach were all considered malignant by visual method. Maximum and mean Standard uptake value (SUV) of cancer were 6.71 +/- 2.75 and 5.46 +/- 2.31, respectively; SUVmax and SUVmean of non-specific FDG avid mass were 2.99 +/- 0.67 and 2.38 +/- 0.51 respectively; SUV of cancer was higher than that of non-specific FDG avid mass (Z = -4.171, Z = -4.195, P < 0.01). CONCLUSIONS: FDG-PET has limited value in differentiating carcinoma of the esophagogastric junction from non-specific FDG avid mass of normal stomach.

Adult↗

PubMed2004

3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism.

SARS 3C-like proteinase has been proposed to be a key enzyme for drug design against SARS. Lack of a suitable assay has been a major hindrance for enzyme kinetic studies and a large-scale inhibitor screen for SARS 3CL proteinase. Since SARS 3CL proteinase belongs to the cysteine protease family (family C3 in clan CB) with a chymotrypsin fold, it is important to understand the catalytic mechanism of SARS 3CL proteinase to determine whether the proteolysis proceeds through a general base catalysis mechanism like chymotrypsin or an ion pair mechanism like papain. We have established a continuous colorimetric assay for SARS 3CL proteinase and applied it to study the enzyme catalytic mechanism. The proposed catalytic residues His41 and Cys145 were confirmed to be critical for catalysis by mutating to Ala, while the Cys145 to Ser mutation resulted in an active enzyme with a 40-fold lower activity. From the pH dependency of catalytic activity, the pK(a)'s for His41 and Cys145 in the wild-type enzyme were estimated to be 6.38 and 8.34, while the pK(a)'s for His41 and Ser145 in the C145S mutant were estimated to be 6.15 and 9.09, respectively. The C145S mutant has a normal isotope effect in D(2)O for general base catalysis, that is, reacts slower in D(2)O, while the wild-type enzyme shows an inverse isotope effect which may come from the lower activation enthalpy. The pK(a) values measured for the active site residues and the activity of the C145S mutant are consistent with a general base catalysis mechanism and cannot be explained by a thiolate-imidazolium ion pair model.

Alanine↗

PubMed2004

Controlled protein assembly on a switchable surface.

The strategy presented in this work supplies a general method of controlling protein assembly on a switchable low-density SAM, which may open a new way to design functional biocomposite films for biosensors or protein chips.

Protein Engineering↗

PubMed2004

Attenuation of zinc-induced neuronal death by the interaction of growth inhibitory factor with Rab3A in rat hippocampal neurons.

We examined the protective effect of growth inhibitory factor (GIF) against zinc-induced neuronal death in rat hippocampal neurons. In an in vitro cell culture system, 300 microM Zn(2+) readily induced death of hippocampal neuronal cells, which was characterized by massive necrosis and a minor degree of apoptosis. Neither the addition of recombinant GIF nor Rab3A alone could rescue these cells from death. However, the combination of GIF with Rab3A could significantly enhance the survival of the hippocampal neurons. This result was supported by both Annexin -V FITC/propidium dual staining and chromosomal DNA analysis. These findings suggest that GIF may inhibit Zn(2+)-induced neuronal death via its interaction with Rab3A.

Animals↗

PubMed2004

Tip110, the human immunodeficiency virus type 1 (HIV-1) Tat-interacting protein of 110 kDa as a negative regulator of androgen receptor (AR) transcriptional activation.

Upon binding to androgen, androgen receptor (AR) can activate expression of target genes through its direct binding to the androgen-responsive elements (AREs), which are located within the target gene promoters and/or enhancers. A number of cellular proteins have been identified as co-regulators to regulate this transactivation process. One common structural feature among these co-regulators is the presence of the LXXLL motif (X, any amino acid), the so-called nuclear receptor (NR) box, through which binding of these regulatory proteins to AR occurs. We have recently shown that Tip110 functions to potentiate the transactivation activity of human immunodeficiency virus type I (HIV-1) Tat protein. In this study, we report that Tip110 is a potent AR-binding protein that can suppress AR activity. Tip110 bound to AR in an NR box-dependent manner and inhibited AREs-mediated reporter gene expression. The inhibitory effects were abolished by removal of the NR box. Moreover, knock-down of the constitutive Tip110 expression significantly augmented AR transcriptional activation. In agreement with these findings, Tip110 overexpression blocked the prostate-specific antigen (PSA) gene, a well characterized target gene of AR from expression in LNCaP cells. Further analysis revealed that Tip110 prevented the complex formation between AR and AREs. Taken together, these results indicate that Tip110 is a negative regulator of AR transcriptional activation, and may be directly involved in AR-related developmental, physiological, and pathological processes.

Amino Acid Motifs↗

PubMed2004

Trends in reported incidences of gastric cancer by tumour location, from 1975 to 1989 in Japan.

BACKGROUND: This study was performed to estimate the incidence of gastric cancer by tumour location and to clarify whether the relative and absolute rates of gastric cancer in Japan changed between 1975 and 1989. METHODS: The stomach was anatomically divided into the upper, middle, and lower thirds. Age- and sex-specific incidences by tumour location were estimated by multiplying the age- and sex-specific national incidences of gastric cancer by the corresponding proportions of tumour location. We studied 171 721 cases of gastric cancer from the Gastric Cancer Registry of Japan. RESULTS: Over 15 years, the proportion of tumours in the upper third of the stomach increased in men but did not change much in women. The proportion of tumours in the middle third of the stomach increased among both men and women while the proportion of tumours in the lower third of the stomach decreased among both men and women. The incidence of tumours in the upper third of the stomach showed an increasing trend among elderly men and women but not among young ones. The incidence of tumours in the lower third of the stomach decreased significantly among men and women of most age groups. CONCLUSIONS: The present study added evidence of disparate trends in the incidence of gastric cancer by tumour location. The separate epidemiological features may indicate different aetiologies as well as changes in the degree of influence of these aetiologies.

Adenocarcinoma↗

PubMed2004

Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution.

Lipid movement between organelles is a critical component of eukaryotic membrane homeostasis. Niemann Pick type C (NP-C) disease is a fatal neurodegenerative disorder typified by lysosomal accumulation of cholesterol and sphingolipids. Expression of yeast NP-C-related gene 1 (NCR1), the orthologue of the human NP-C gene 1 (NPC1) defective in the disease, in Chinese hamster ovary NPC1 mutant cells suppressed lipid accumulation. Deletion of NCR1, encoding a transmembrane glycoprotein predominantly residing in the vacuole of normal yeast, gave no phenotype. However, a dominant mutation in the putative sterol-sensing domain of Ncr1p conferred temperature and polyene antibiotic sensitivity without changes in sterol metabolism. Instead, the mutant cells were resistant to inhibitors of sphingolipid biosynthesis and super sensitive to sphingosine and C2-ceramide. Moreover, plasma membrane sphingolipids accumulated and redistributed to the vacuole and other subcellular membranes of the mutant cells. We propose that the primordial function of these proteins is to recycle sphingolipids and that defects in this process in higher eukaryotes secondarily result in cholesterol accumulation.

Amino Acid Sequence↗

PubMed2004

Induction of C chemokine XCL1 (lymphotactin/single C motif-1 alpha/activation-induced, T cell-derived and chemokine-related cytokine) expression by HIV-1 Tat protein.

HIV-1 Tat has been proposed as a key agent in many AIDS-related disorders, including HIV-1-associated neurological diseases. We have recently shown that Tat expression induces a significant increase in T lymphocytes in the brains of Tat transgenic mice. The CNS infiltration of T lymphocytes has been noted in AIDS patients. In the present study using this unique genetic system we attempted to understand the underlying mechanisms of Tat expression-induced infiltration of T lymphocytes by examining chemokine expression. RNase protection assay revealed that in addition to CCL2 (monocyte chemoattractant protein-1), CCL3 (macrophage inflammatory protein-1alpha (MIP-1alpha)), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL2 (MIP-2), and CXCL10 (inducing protein-10), XCL1 (lymphotactin/single C motif-1alpha/activation-induced, T cell-derived and chemokine-related cytokine) was identified to be up-regulated by Tat expression. XCL1 is a C chemokine and plays a specific and important role in tissue-specific recruitment of T lymphocytes. Thus, we further determined the relationship between Tat and XCL1 expression. Tat-induced XCL1 expression was further confirmed by XCL1-specific RT-PCR and ELISA. Combined in situ hybridization and immunohistochemical staining identified astrocytes, monocytes, and macrophages/microglia as XCL1-producing cells in vivo. Using human astrocytes, U87.MG cells, as an in vitro model, activation of XCL1 expression was positively correlated with Tat expression. Moreover, the XCL1 promoter-driven reporter gene assay showed that Tat-induced XCL1 expression occurred at the transcriptional level. Taken together, these results demonstrate that Tat directly trans-activated XCL1 expression and suggest potential roles of Tat-induced XCL1 expression in the CNS infiltration of T lymphocytes during HIV-1 infection and subsequent HIV-1-induced neurological diseases.

Amino Acid Motifs↗

PubMed2004

Microscopic determination of tetracycline based on aluminum-sensitized fluorescence of a self-ordered ring formed by a sessile droplet on glass slide support.

A fluorescent microscopic determination of trace amount of tetracycline is reported based on the aluminum-sensitized fluorescence effect of a self-ordered ring formed by a sessile droplet on glass slide support. Since the evaporative loss of the solvent from the edge wedge of the droplet that is spotted on a hydrophobic-treated glass slide, an outward capillary flow of the interior solvent of the droplet occurs. The resulted outward capillary flow then carries the solute to the perimeter of the droplet spot where the solute accumulates to form a fluorescent self-ordered ring (SOR). Depending on the spotted volume of the aluminum-tetracycline chelate solution, different size of SOR with the outer diameter (o.d.) less than 1.1mm and the ring belt width less than 21.6 microm can be obtained. Data analysis for the imaged SOR by using a digitalized CCD camera showed that the chelate molecule across the fluorescent SOR belt section follows a Gaussian distribution, and the maximum fluorescent intensity (I(max)) was found to be proportional to tetracycline content. When a 0.1 microl droplet was spotted on the solid surface, tetracycline in the range of 7.5-800.0 fmol (or 7.9 x 10(-8) to 800.0 x 10(-8)moll (-1)) can be detected, and the limit of detection can reach 0.8 fmol (or 7.9 x 10(-9) moll (-1)). With present method, the contents of tetracycline in capsule, tablet, urine and fresh milk were satisfactorily detected with the recoveries of 97.0-106.5% and RSD of 1.2-4.2%, correspondingly.

Aluminum↗

PubMed2004

[Proliferation of specific cytotoxic T lymphocytes induced by immunoglobulin heavy chain framework region-derived antigenic nonapeptides].

OBJECTIVE: To identify that immunoglobulin heavy chain framework regions-derived peptides function as cytotoxic T lymphocytes epitopes. METHODS: Seven IgHV gene families were respectively amplified by PCR and directly sequenced for 108 acute lymphoblastic leukemia cases. Sequences available were translated into amino acid sequences. Bioinformatics were applied for analyzing recombination patterns and gene mutations of the IgHV genes. Softwares SYFPEITHI and BIMAS were used for predicting the T cell epitopes in the immunoglobulin heavy chain variable regions. To determine whether the predicted peptides have immunogenicity, a IgHV1 family nonapeptide QLVQSGAEV was synthesized as a representation and T2 binding assay of this peptide was performed, inducing proliferation of T cells from normal HLA-A * 0201 peripheral blood lymphocytes (PBLs) with QLVQSGAEV-loaded antigen presenting cells, and detecting the proliferating T cells by HLA-A * 0201/QLVQSGAEV tetramers. RESULTS: Complete IgHV gene rearrangements were identified in 66% cases. Among 40 B-ALL IgHV sequences available, 26 were predicted for antigenic nonapeptides that are likely to bind to HLA-A * 0201 molecule. Twelve peptides were acquired. Except one peptide derived from CDR3, 10 (83%) peptides were located in the immunoglobulin heavy chain framework regions. Moreover B-ALL belonging to the same IgHV family shared 1 - 2 peptides. Synthesized peptide QLVQSGAEV up-regulated HLA-A * 0201 expression 1.63 times on T2 cell surface. PBLs from a normal HLA-A * 0201 donor were stimulated with QLVQSGAEV-loaded autologous PBMCs and T2, the CD8(+) tetramer(+) cells in gated lymphocyte population increased from 1.64% after the first stimulation to 82.57% after the third stimulation. CONCLUSION: Immunoglobulin heavy chain framework region genes encode IgHV family-specific peptides recognized by CTLs. Specific CTLs remain in human peripheral T cell repertoire. Immunoglobulin heavy chain framework-derived peptides function as T cell epitopes to induce the proliferation of specific CTLs.

Adolescent↗

PubMed2004

[The effect of basic fibroblast growth factor on angiogenesis and on the expression of basic fibroblast growth factor and vascular endothelial growth factor in acute infarcted myocardium].

OBJECTIVE: To evaluate the effect of intramyocardial administration of basic fibroblast growth factor (bFGF) on the angiogenesis and on the expression of bFGF and vascular endothelial growth factor (VEGF) in infarcted myocardium. METHODS: Twenty-four mongrel dogs were randomized into control group and therapeutic group. Acute myocardial infarction was made by ligation of the left anterior descending coronary artery distal to its first diagonal branch. After coronary artery was occlused, 50 micrograms of basic fibroblast growth factor in 15 ml of normal saline were injected into the infarcted myocardium and its border zone in therapeutic group, whereas the same volume of normal saline alone was used in control dogs. Every 3 dogs in each group was studied on the 1st day, the 3rd day, the 10th day and the 17th day after surgery respectively. With sensitivity encoded technique, cine MR was performed on each dog before euthanasia to evaluate the cardiac function. Angiogenesis and the expression of VEGF and bFGF were evaluated by immunohistochemical studies with factor VIII and the antibodies of VEGF and bFGF. RESULTS: In therapeutic group, left ventricular ejection fraction, improved markedly since the 10th day after injection of bFGF. Microvessel density was higher in the therapeutic group than in the control group except on the first day. VEGF and bFGF expressed more in the therapeutic group. CONCLUSION: Intramyocardial administration of bFGF is useful in increasing the growth of microvessels and improving the left ventricular function in acute myocardial infarction.

Animals↗

PubMed2004

Transplantation of glial-restricted precursor cells into the adult spinal cord: survival, glial-specific differentiation, and preferential migration in white matter.

Glial-restricted precursor (GRP) cells are among a number of candidate cells for transplantation repair of CNS injury. The isolation and characterization of these cells in vitro have been described previously, but their in vivo properties are not well understood. We examined the fate and migration of grafted fetal GRP cells harvested from alkaline phosphatase-expressing transgenic rats into intact and injured spinal cord. Transplanted GRP cells survived for at least 6 weeks and differentiated along astrocytic and oligodendrocytic but not neuronal lineages. Cells grafted into the intact spinal cord exhibited robust migration along longitudinal white matter tracts and by 6 weeks migrated more than 15 mm. In contrast, migration of GRP cells in the gray matter was very limited. We then examined the phenotypic properties of proliferating endogenous precursors in response to injury by BrdU labeling. The predominant proliferating population seen after injury consisted of GRP-like cells with Nkx2.2/olig2 phenotype. Incorporation of BrdU by endogenous cells suggests that the environment provides proliferation signals and is permissive to glial precursor survival. To test if exogenous GRP cells would respond similarly, we transplanted GRP cells into a lateral funiculus injury. GRP cells survived and differentiated along glial lineages and migrated along white matter tracts in the injured spinal cord. Directed homing toward the lesion was not seen and there was no significant bias in differentiation between cells transplanted into injured and uninjured spinal cord. GRP cell transplants may therefore provide a cellular transplant that can respond to appropriate endogenous cues to produce therapeutic molecules and new glial cells after injury.

Animals↗

PubMed2004

Olig genes are expressed in a heterogeneous population of precursor cells in the developing spinal cord.

Recent results from multiple laboratories have identified Olig genes as important in regulating glial differentiation. Here we show that Olig2 expression at early stages of development (prior to E16.5) identifies a domain in the developing spinal cord, which contains a heterogeneous population of progenitors that includes stem cells and glial progenitors. We show that Nkx2.2 and Olig2, which are present initially in nonoverlapping domains, are coexpressed at later stages, likely due to a second wave of Olig expression. We find that Olig1, like Olig2, is present in cells that coexpress astrocytic and radial glial markers and that Olig1/2 double knockouts lead to a loss of oligodendrocytes with preservation of NG2 expression. These results coupled with previously published data indicate that Olig1/2 and Nkx2.2, while clearly important in regulating early progenitor cell differentiation, do not unambiguously demonstrate the existence of an oligodendrocyte-neuron precursor or negate the existing retroviral lineage and clonal analysis data that suggest the existence of other types of precursors such as oligodendrocyte-astrocyte precursors or neuronal precursors.

Animals↗

PubMed2004

CD44 overexpression by oligodendrocytes: a novel mouse model of inflammation-independent demyelination and dysmyelination.

The CD44 transmembrane glycoprotein family has been implicated in cell-cell adhesion and cell signaling in response to components of the extracellular matrix but its role in the nervous system is not understood. CD44 proteins are elevated in Schwann cells and oligodendrocytes following nervous system insults, in inflammatory demyelinating lesions, and in tumors. Here, we tested the hypothesis that elevated CD44 expression influences Schwann cell and oligodendrocyte functions by generating transgenic mice that express CD44 under the control of the 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) promoter. These mice failed to develop peripheral nerve or CNS tumors. However, they did develop severe tremors that were associated with CNS dysmyelination and progressive demyelination. Loss of CNS myelin was not due to alterations in early oligodendrocyte precursor differentiation, proliferation, or survival. Myelination in the PNS appeared normal. In no instance was there any evidence of an inflammatory response that could account for the loss of CNS myelin. These findings suggest that CNPase-CD44 mice are a novel model for noninflammatory progressive demyelinating disease and support a potential role for CD44 proteins expressed by glial cells in promoting demyelination.

Animals↗