PubMed Health⌕ Search

Biomedical subjects

Y Liu

Publications and source records attributed to Y Liu.

At least 343 records · Page 19Linked to original sources
PubMed2001

Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF-beta-mediated epidermal homeostasis.

Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for epithelial growth and can alter the differentiation of keratinocytes. Transduction of TGF-beta signaling depends on the phosphorylation and activation of Smad proteins by heteromeric complexes of ligand-specific type I and II receptors. To understand the function of TGF-beta and activin-specific Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the control of keratin 14 promoter. Overexpression of Smad2 increases endogenous Smad4 and TGF-beta 1 expression while heterozygous loss of Smad2 reduces their expression levels, suggesting a concerted action of Smad2 and -4 in regulating TGF-beta signaling during skin development. These transgenic mice have delayed hair growth, underdeveloped ears, and shorter tails. In their skin, there is severe thickening of the epidermis with disorganized epidermal architecture, indistinguishable basement membrane, and dermal fibrosis. These abnormal phenotypes are due to increased proliferation of the basal epidermal cells and abnormalities in the program of keratinocyte differentiation. The ectodermally derived enamel structure is also abnormal. Collectively, our study presents the first in vivo evidence that, by providing an auto-feedback in TGF-beta signaling, Smad2 plays a pivotal role in regulating TGF-beta-mediated epidermal homeostasis.

Animals↗
PubMed2001

Utilizing biomimetic oligopeptides to probe fibronectin-integrin binding and signaling in regulating macrophage function in vitro and in vivo.

Biomimetic oligopeptides were employed to elucidate the molecular mechanisms of fibronectin-integrin interaction in regulating macrophage function. Oligopeptides were designed based on of the functional structure of fibronectin and grafted onto a polymer network containing polyethyleneglycols. Macrophage adhesion was independent of the peptide identity that contained sequence RGD, PHSRN, PRRARV, or combinations thereof in an integrin-dependent fashion in vitro. However, integrin-dependent foreign body giant cell (FBGC) formation in vitro was highly dependent on both RGD and PHSRN in a single peptide formulation and with a specific orientation. In vivo results showed that peptide identity played a minimal role in modulating the host inflammatory response and adherent macrophage density. RGD-containing peptides mediated a rapid FBGC formation by 4 days of implantation by significantly increasing both the number of macrophages that participate in the cell fusion process and the rate of cell fusion. Both RGD and PHSRN domains were important in mediating FBGC formation at later implantation periods. In vitro intracellular signaling studies revealed that the requirement of protein tyrosine kinase and serine/threonine kinase activation and cross-talk compensation for macrophage adhesion dynamically varied with surfaces and culture time. Protein kinase C-dependent adhesion was related to RGD and PHSRN sequences, and to the sequence orientation thereof in a form of GGGRGDGGGGGGPHSRNG. Furthermore, we observed a multiple effect of the mitogen-activated protein kinase/extracellular-signal-regulated kinase signaling factor in mediating macrophage adhesion, which depended on the method of ligand immobilization. These findings represent a mechanistic correlation between the role of substrates and protein functional architectures in ligand-receptor recognition and post-ligation signaling events that control cellular behavior in vitro and in vivo.

Animals↗
PubMed2001

Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus.

Neuregulins are highly expressed in the CNS, especially in cholinergic neurons. We have examined the effect of neuregulin on nicotinic acetylcholine receptors (nAChRs) in neurons dissociated from the rat hippocampus. Rapid application of acetylcholine (ACh) induced a rapidly rising and decaying inward current in some of the neurons, which was completely blocked by methyllycaconitine, a specific antagonist of the alpha7 subunit of the nAChR. When the cells were treated with 5 nm neuregulin (NRG1-beta1) for 2-4 d, a twofold increase in amplitude of the peak ACh-induced current was observed, and there was a comparable increase in (125)I-alpha-bungarotoxin binding. The fast ACh-induced peak current was prominent in large neurons that also contained GABA immunoreactivity. These presumptive GABAergic neurons constituted approximately 10% of neurons present in 7- to 9-d-old cultures. In addition to the large inward peak current, ACh also evoked transmitter release from presynaptic nerve terminals. Pharmacologic experiments indicated that the shower of PSCs was mediated by glutamate, with a small minority caused by the action of GABA. Chronic exposure to NRG1-beta1 increased the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC. NRG1-beta1 also increased the percentage of neurons that exhibited ACh-evoked PSCs.

Acetylcholine↗
PubMed2001

The role of CD47 in neutrophil transmigration. Increased rate of migration correlates with increased cell surface expression of CD47.

CD47, a cell surface glycoprotein, plays an important role in modulating neutrophil (PMN) migration across endothelial and epithelial monolayers. Here we show that anti-CD47 monoclonal antibodies (mAbs) delay PMN migration across collagen-coated filters or T84 epithelial monolayers toward the chemoattractant formylmethionylleucylphenylalanine (fMLP). Despite delayed transmigration by anti-CD47 mAbs, the numbers of PMN migrating across in either condition were the same as in the presence of control non-inhibitory mAbs. Cell surface labeling and immunoprecipitation demonstrated upregulation of CD47 to the PMN cell surface with kinetics similar to those of the transmigration response. Subcellular fractionation studies revealed redistribution of CD47 from intracellular compartments that co-sediment with secondary granules to plasma membrane-containing fractions after fMLP stimulation. Experiments performed to investigate potential signaling pathways revealed that inhibition of tyrosine phosphorylation with genistein reversed the anti-CD47-mediated PMN migration delay, whereas inhibition of phosphatidylinositol 3-kinase only partially reversed anti-CD47 effects that correlated with a rapid increase in PMN cell surface CD47. Analysis of the contribution of epithelial-expressed CD47 to PMN transmigration revealed that PMN migration across CD47-deficient epithelial monolayers (CaCO2) was significantly increased after stable transfection with CD47. These results suggest that cell surface CD47 and downstream tyrosine phosphorylation signaling events regulate, in part, the rate of PMN migration during the inflammatory response.

Antibodies, Monoclonal↗
PubMed2001

[Risk factors of lung cancer and relevant comprehensive preventive strategy--a cohort study in Xuanwei, Yunnan Province, China].

OBJECTIVE: To systematically analyze the risk factors of lung cancer in Xuanwei, Yunnan Province, an area with a high prevalence of lung cancer, and in view of the above to propose a comprehensive preventive strategy. METHODS: A cohort study of 42,434 Xuanwei farmers who were born 1917-195, and still alive on 1st January 1976 was carried out from 1992 to 1996 with a follow-up time of 21 years. The data collection was done in two steps. A retrospective cohort study was conducted in the form of questionnaire survey in 1992 to understand the health situation of the interviewees from 1st January 1976 to 31st December 1991. In the second stage, a prospective cohort study was conducted to review the death records of the interviewees from 1st January 1992 to 31st December 1996. The data thus collected were analyzed by the Mantel-Haenszel analysis method, COX model and risk state analysis method. RESULTS: Indoor air pollution caused by biturminous coal burning is the major risk factor of lung cancer in Xuanwei. Stove improvement decreased the lung cancer mortality rate in both male and female subjects, but its beneficial can be recognized at least 10 years after. Smoking is another important risk factor of lung cancer in males in Xuanwei. In course of a long time since stove improvement smoking will become the major risk factor of lung cancer. The risky factors can be arranged in sequence of riskiness from high to low as bituminous coal burning, family history of lung cancer, personal history of chronic bronchitis, and smoking in males; and bituminous coal burning, family history of lung cancer, and personal history of chronic bronchitis in females. The risk state classification model established upon the basis of risk state analysis can be used in identifying effectively high risk population quantitatively for local administrators of health as well as for local residents. CONCLUSION: According to the comprehensive strategy for lung cancer control in Xuanwei, priority should be given to primary prevention with three steps: firstly to further reduce indoor air pollution by means of stove improvement and ventilation improvement, secondly strengthen smoking cessation, and thirdly to carry out chemoprevention and susceptibility study of lung cancer among high risk populations.

Air Pollution, Indoor↗
PubMed2001

High glucose impairs voltage-gated K(+) channel current in rat small coronary arteries.

Hyperglycemia is associated with impaired endothelium-dependent dilation that is due to quenching of NO by superoxide (O(2)(. -)). In small coronary arteries (CAs), dilation depends more on smooth muscle hyperpolarization, such as that mediated by voltage-gated K(+) (Kv) channels. We determined whether high glucose enhances O(2)(.-) production and reduces microvascular Kv channel current and functional responses. CAs from Sprague-Dawley rats were incubated 24 hours in medium containing either normal glucose (NG, 5.5 mmol/L D-glucose), high glucose (HG, 23 mmol/L D-glucose), or L-glucose (LG, 5.5 mmol/L D-glucose and 17 mmol/L L-glucose). O(2)(.-) production was increased in HG arteries. Whole-cell patch clamping showed a reduction of 4-aminopyridine (4-AP)-sensitive current (Kv current) from smooth muscle cells of HG CAs versus NG CAs or versus LG CAs (peak density was 9.95+/-5.3 pA/pF for HG versus 27.8+/-6.8 pA/pF for NG and 28.5+/-5.2 pA/pF for LG; P<0.05). O(2)(.-) generation (xanthine+xanthine oxidase) decreased K(+) current density, with no further reduction by 4-AP. Partial restoration was observed with superoxide dismutase and catalase. Constriction to 3 mmol/L 4-AP was reduced in vessels exposed to HG (13+/-5%, P<0.05) versus NG (30+/-7%) or LG (34+/-4%). Responses to KCl and nifedipine were not different among groups. Superoxide dismutase and catalase increased contraction to 4-AP in HG CAs. This is the first direct evidence that exposure of CAs to HG impairs Kv channel activity. We speculate that this O(2)(.-)-induced impairment may reduce vasodilator responsiveness in the coronary circulation of subjects with coronary disease or its risk factors.

4-Aminopyridine↗
PubMed2001

Cutting edge: integration of human T lymphocyte cytoskeleton by the cytolinker plectin.

Chemokine-induced polarization of lymphocytes involves the rapid collapse of vimentin intermediate filaments (IFs) into an aggregate within the uropod. Little is known about the interactions of lymphocyte vimentin with other cytoskeletal elements. We demonstrate that human peripheral blood T lymphocytes express plectin, an IF-binding, cytoskeletal cross-linking protein. Plectin associates with a complex of structural proteins including vimentin, actin, fodrin, moesin, and lamin B in resting peripheral blood T lymphocytes. During chemokine-induced polarization, plectin redistributes to the uropod associated with vimentin and fodrin; their spatial distribution indicates that this vimentin-plectin-fodrin complex provides a continuous linkage from the nucleus (lamin B) to the cortical cytoskeleton. Overexpression of the plectin IF-binding domain in the T cell line Jurkat induces the perinuclear aggregation of vimentin IFs. Plectin is therefore likely to serve as an important organizer of the lymphocyte cytoskeleton and may regulate changes of lymphocyte cytoarchitecture during polarization and extravasation.

Actins↗
PubMed2001

Functional quantification of DNA-binding proteins p53 and estrogen receptor in cells and tumor tissues by DNA affinity immunoblotting.

Functional assays of proteins can monitor the consequences of defects attributable to posttranslational activating or inhibitory events as well as to genetic mutations. Such assays promise to permit evaluation of cooperating oncogenic or tumor suppressor pathways in cells and tumors. As a step toward realizing this promise, we designed the DNA affinity immunoblotting (DAI) method to measure the activities of multiple sequence-specific DNA-binding proteins simultaneously [initially p53 and estrogen receptor (ER)] in lysates of cells or frozen tumor tissues. DAI is a novel application of biotin/streptavidin affinity chromatography and immunoblotting. The p53 and ER proteins in cell or tissue lysates were bound to biotinylated, specific DNA probes, retrieved using a streptavidin-conjugated matrix, and then quantified in parallel with total protein by immunoblotting. The assay results were reproducible and specifically correlated with the known functional status of p53 in mouse and human cells of known p53 genotype, including those with low levels of p53 protein. ER immunohistochemistry of human breast samples, which is highly correlated with functional status and prognosis in human breast cancer, was also highly correlated with DNA binding activity results by DAI. In contrast, the p53 protein in cells is frequently expressed but inactive, potentially accounting for the lack of strict correlation of p53 immunohistochemical or mutational status with tumor response to chemotherapy. DAI offers a new means of molecular profiling and monitoring of p53 and other DNA-binding protein activities in cells and tumors. DAI has applications in the detection and identification of covalently modified forms of DNA-binding proteins and in the identification of their interacting proteins in complex with DNA.

Animals↗
PubMed2001

Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia.

Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles. We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia is mediated by the induction of distinct cytokines and chemokines and is independent of tumor necrosis factor-alpha signaling. We have previously proposed a crucial role for heme oxygenase-1 (HO-1) in protecting cardiomyocytes from hypoxic stress, and potent anti-inflammatory properties of HO-1 have been reported in models of tissue injury. We thus established transgenic mice that constitutively express HO-1 in the lung and exposed them to chronic hypoxia. HO-1 transgenic mice were protected from the development of both pulmonary inflammation as well as hypertension and vessel wall hypertrophy induced by hypoxia. Significantly, the hypoxic induction of proinflammatory cytokines and chemokines was suppressed in HO-1 transgenic mice. Our findings suggest an important protective function of enzymatic products of HO-1 activity as inhibitors of hypoxia-induced vasoconstrictive and proinflammatory pathways.

Animals↗
PubMed2001

Quinoline-4-acetamides as sPLA(2) inhibitors.

Quinoline-4-acetamides were designed as potential phospholipase A(2) inhibitors by structural based method and synthesized. The chemical structures of the obtained compounds were confirmed by elemental analyses, 1H NMR and MS. Preliminary bioassay study shows that quinoline-4-acetamides display certain inhibition to sPLA(2).

Acetamides↗
PubMed2001

Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis.

Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease, multiple sclerosis (MS). Heme oxygenase-1 (HO-1) is a heat shock protein induced by oxidative stress. HO-1 metabolizes heme to the antioxidant bilirubin and carbon monoxide, and represents a powerful endogenous defensive mechanism against free radicals in many diseases. However, the role of this important enzyme in EAE remains unknown. In this study, we showed high expression of HO-1 in lesions of EAE, and demonstrated that hemin, an inducer of HO-1, inhibited EAE effectively. In contrast, tin mesoporphyrin, an inhibitor of HO-1, markedly exacerbated EAE. Our results suggest that endogenous HO-1 plays an important protective role in EAE, and that targeted induction of HO-1 overexpression may represent a new therapy for the treatment of multiple sclerosis.

Animals↗
PubMed2001

Photodynamic action of actinomycin D: an EPR spin trapping study.

Actinomycin D is one of the most widely studied anticancer antibiotic that binds to both double-stranded and single-stranded DNA, and this binding greatly enhances the DNA photosensitization. By use of electron paramagnetic resonance spin trapping techniques, both superoxide radical anion and the radical anion of actinomycin D were identified as important intermediates in the photodynamic process. A mechanism of electron transfer from a DNA base to excited actinomycin D was proposed. These novel findings may shed new light on future application of this drug in photodynamic therapy or cleavage of DNA in unique and controllable ways.

Antibiotics, Antineoplastic↗
PubMed2001

Simultaneous measurement of anandamide and 2-arachidonoylglycerol by polymyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: increase in endogenous cannabinoids in the sera of patients with endotoxic shock.

Anandamide (ANA) and 2-arachidonoylglycerol (2-AG), two endogenous cannabinoids, can be generated by activated macrophages and platelets, respectively, in the context of endotoxic shock, and are proposed to play a crucial role in the induction of the shock-related hypotension. Taking advantage of our recently discovered function of polymyxin B (PMB) binding to ANA and 2-AG, we developed a new method for measuring ANA and 2-AG by applying PMB-immobilized beads to selectively adsorb them in biological fluids, instead of organic solvent extraction. The eluate from beads can be directly fractionated by reverse-phase high-performance liquid chromatography (HPLC), and the fractionations corresponding to authentic ANA and 2-AG are collected and derivatized with fluorogenic reagent and subsequently quantified by HPLC with fluorometric detection. The calibration graphs of ANA and 2-AG were linear over a range of 1 to 500 pmol/ml. The limits of detection for ANA and 2-AG were 20 and 50 fmol, respectively. Intraassay precision was 2.24-4.25 and 3.47-5.44%, and interassay was 4.05-6.14 and 4.92-7.28% for ANA and 2-AG, respectively. Using this method, we first determined a 4-fold and 3-fold higher level of ANA and 2-AG, respectively, in the sera of patients with endotoxic shock than in normal serum. This finding should help in elucidating the role of the endogenous cannabinoids in the hypotension of human endotoxic shock. This method is rapid, sensitive, and reliable for simultaneously quantifying ANA and 2-AG in biological fluids, and has potential for clinical usage.

Adsorption↗
PubMed2001

The effect of bone morphogenetic protein-7 (BMP-7) on functional recovery, local cerebral glucose utilization and blood flow after transient focal cerebral ischemia in rats.

Bone morphogenetic protein-7 (BMP-7) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on functional recovery, local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague--Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. Rectal and cranial temperatures were regulated at 37.0--37.5 degrees C. BMP-7 or vehicle (volume, 25 microl) was administered intracisternally in a blinded fashion at 24 h after MCAo. Neurological status was evaluated during occlusion (60 min) and daily for 2 days after MCAo. In matched animal groups, LCMRglu was measured autoradiographically with [(14)C]2-deoxyglucose (2-DG) and LCBF with [(14)C]iodoantipyrine 48 h after MCAo. Four animals groups were studied: LCMRglu series (BMP-7, n=7; vehicle, n=8); LCBF series (BMP-7, n=6; vehicle, n=8). Average three-dimensional image data sets were constructed for each group and were compared by pixel-based statistical methods. Rectal and cranial temperatures, mean blood pressure, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the total neurological score compared to vehicle at 48 h after MCAo (7.3+/-0.4 vs. 9.0+/-0.2, respectively; P<0.0003). Compared to vehicle-rats, BMP-7 enhanced glucose utilization in the basal ganglia ipsilateral to stroke and improved LCBF in ipsilateral subthalamus, but decreased LCBF and LCMRglu in contralateral cortical regions.

Animals↗
PubMed2001

Observation of Andreev surface bound states in the 3-K phase region of Sr2RuO4.

The tunneling spectrum of the superconducting phase with Tc approximately 3.0 K has been measured in the Ru-embedded region of Sr2RuO4 using cleaved junctions. A sharp zero-bias conductance peak (ZBCP) has been observed below 3 K. All characteristics of this ZBCP suggest that it originates from Andreev surface bound states, indicating that the pairing in the 3-K phase is also non- s-wave. Below the bulk Tc of Sr2RuO4 (approximately 1.5 K), a crossover from sharp to bell-shaped ZBCP was found. This supports the theory that there is a phase transition in the 3-K phase region near the bulk Tc.

Journal Article↗
PubMed2001

Capillary-electrochromatographic separations with copolymeric reversed-stationary phase and ion-exchanger-packed columns.

A macroporous, spherical, 7 microm, polystyrene-divinylbenzene (PS-DVB), reversed-phase adsorbent (PRP-1) was evaluated as a stationary phase for the capillary electrochromatographic (CEC) separation of neutral, acidic, and basic analytes of pharmaceutical interest. Electroosmotic flow (EOF) for a PRP-1 packed capillary is nearly constant over the pH 2 to 10 range and is higher than for a silica-based C18 packed capillary on the acidic side. EOF increases with an increase in buffer acetonitrile concentration or as applied potential increases. As analyte hydrophobicity increases, analyte retention and migration time increases. Increasing buffer acetonitrile concentration reduces analyte partitioning with the PS-DVB stationary phase and analyte retention and migration time decreases. When exchange sites are present on the PS-DVB copolymer, EOF (EOF is reversed for the anion-exchanger) increases as the exchange capacity increases. An increased exchange capacity also reduces partitioning of the analyte with the PS-DVB matrix and analyte retention and migration time decrease. Because of excellent stability in an acid environment, the PRP-1 packed capillary can be used in strong acid buffer solution and weak acid and base analytes depending on pKa values can be separated as neutral species and cations, respectively. CEC separations on a PRP-1 capillary of neutral steroids, weak base pharmaceuticals (separation as cations), purines and pyrimidines (as cations), fatty acids (as undissociated species), and sulfa derivatives (as cations) are described. Efficiency for the PRP-1 packed capillary for acetone or thiourea as the analyte is about 6 x 10(4) plates m(-1).

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2001

Protective effect of metallothionein against the toxicity of cadmium and other metals(1).

Metallothionein (MT) is a small-molecular weight, cysteine-rich protein that binds metals. The protective role of MT in Cd toxicity is well established but its ability to protect against toxicity of other metals remains unclear. In this study, wild-type and MT-I and -II null mice (MT-null mice) were used to determine whether MT is protective against the lethality of not only Cd but also Zn, Cu, Fe, Pb, Hg and As. Following daily subcutaneous administration of an increasing dose of each metal, starting with a low, non-toxic dose, we compared the cumulative median lethal dose (LD(50)) of each metal between wild-type and MT-null mice. The LD(50) of Cd for wild-type mice was 6.9-fold higher than for MT-null mice. The LD(50) of Zn was 2.4-fold higher for wild-type mice than for MT-null mice, and 1.4-fold higher for Cu and As. The LD(50) of Hg was 1.3-fold higher for wild-type mice than for MT-null mice, but this was not statistically significant. No difference in LD(50) values was observed between wild-type and MT-null mice following Pb and Fe administration. These results suggest that MT is an important protein in the cellular defense against Cd toxicity and lethality, but it provides much less protection against the lethality of the other metals.

Animals↗