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M Liu

Publications and source records attributed to M Liu.

At least 469 records · Page 26Linked to original sources
PubMed1996

Structure-activity and mechanistic relationships: the effect of chemical overlap on structural overlap in data bases of varying size and composition.

Similarities between structures in SAR models derived from different data bases, termed 'structural overlap', can be used for determining mechanistic similarities, e.g., mutagenicity vs. carcinogenicity. However, the structural overlap may be affected by the proportion of common chemicals in the data bases, termed 'chemical overlap'. In order to refine our ability to determine mechanistic similarities, we investigated the relationship between chemical and structural overlap as well as the effect of the ratio of active to inactive chemicals and data base size on that relationship, using a data base of Salmonella mutagenicity. A linear relationship between chemical overlap and structural overlap with a slope of 0.332 was found. For data bases of 210, 300 and 390 chemicals, this relationship was consistent. Differences in ratios of active to inactive chemicals, i.e., 1:2, 1:1 and 2:1, did not appear to affect the linear model. We can use this relationship to adjust for chemical overlap when examining the structural overlap of data bases developed for different endpoints to determine the extent of mechanistic similarities.

Databases, Factual↗
PubMed1996

Estimation of the optimal data base size for structure-activity analyses: the Salmonella mutagenicity data base.

In the present study, the effects of data base size on predictivity, informational content and structural overlap of derived Structure-Activity Relationship (SAR) models were investigated. It was found that indices of predictivity (i.e., sensitivity, specificity, and concordance between experimental and predicted results (OCP) increased with increasing size of the data base until the range is 300-400 chemicals, at which point they plateau. The greater the size of the data base, the greater the informational content of the model; however, the rate of this increase is no longer optimal when the size of the data base exceeds 400 chemicals.

Carcinogens↗
PubMed1996

Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells.

Inhibition by antipsychotic drugs of voltage-gated L-type Ca2+ channels was characterized in rat neuronal cell line pheochromocytoma PC12 cells. Under whole-cell voltage-clamp, haloperidol and chlorpromazine (1-100 microM) inhibited Ba2+ current permeating through Ca2+ channels. Fluspirilene and pimozide the Ba2+ current at lower concentrations (fluspirilene, 0.1 pM to 1 nM; pimozide 10 pM to 1 microM). Effects of dopamine receptor antagonists and calmodulin antagonists were tested because antipsychotic drugs are known to exhibit these pharmacological activities. Sulpiride (1 and 10 microM), an antagonist to dopamine D2 receptors, and SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine; 1 and 10 microM), an antagonist to dopamine D1 receptors, also inhibited the Ba2+ current. As for calmodulin antagonists, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 microM) as well as calmidazolium (10 nM to 1 microM) reduced the Ba2+ current. The inhibition by haloperidol or fluspirilene of the Ba2+ current was not affected when GTP in intracellular solution was replaced with GDP beta S. These properties of the Ca2+ channel inhibition are discussed by comparing with those of the K+ channel inhibition and in relation to therapeutic relevance.

Animals↗
PubMed1996

High-resolution diffusion and relaxation edited one- and two-dimensional 1H NMR spectroscopy of biological fluids.

A new approach to the characterization of biomolecules in whole biological fluids is presented based on simplification of 1H NMR spectra by utilizing differences in molecular diffusion coefficients alone and combinations of relaxation and diffusion parameters. New NMR pulse sequences incorporating both spectral editing features together with solvent water resonance elimination are presented. The methods are exemplified using whole human blood plasma, and it is shown that it is possible to obtain NMR spectra of the slowly diffusing species (generally large molecules) by diffusion editing, the slowly relaxing species (generally small molecules) by spin relaxation editing, or spectra showing any range of molecular mobility using a combination of the two methods. The diffusion-based editing methods are also applicable to the selection of resonances in two-dimensional NMR spectroscopy of biofluids, and we show this for the first time by the production of 1H-1H diffusion-edited TOCSY spectra of human blood plasma where the resonance intensities are weighted according to the molecular diffusion coefficient. In this case, by measuring a diffusion-edited 1H-1H TOCSY NMR spectrum of plasma, it is possible to obtain signals from only the macromolecular components, and this may be of benefit in the analysis of blood lipoproteins. In complex biofluids, the combination of diffusion and relaxation editing brings about considerable spectral simplification leading to an easier resonance assignment process. We also demonstrate the production of 1H NMR spectra with intensities corresponding to diffusion coefficient rather than number of protons, and this opens up new possibilities for pattern recognition classification of samples based on altered molecular mobility features of biofluid components.

Blood↗
PubMed1996

Regulation by cAMP-dependent protein kinease of a G-protein-mediated phospholipase C.

The heterotrimeric G proteins mediate a variety of cellular processes by coupling transmembrane receptors to different effector molecules, including adenylyl cyclases and inositol-phospholipid-specific phospholipase C (PLC)1-3. Activation of adenylyl cyclases results in the production of cyclic AMP and activation of cAMP-dependent protein kinase (PKA). Phospholipase C catalyses the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) to generate diacylglycerol and inositol-1,4,5-triphosphate (InsP2), leading to the activation of protein kinase C (PKC) and the mobilization of intracellular calcium. The various PLC isoforms appear to be activated by different receptors, and in some cases by different G-protein components. There are four well-characterized forms of PLC-beta and all of them are activated to various extents by the G alpha q family of G proteins. Specific activation of PLC isoforms beta 2 and beta 3 by G-protein beta gamma subunits has also been reported. Although it has been suggested that PLC activity might be modulated by the adenylyl cyclase pathway, no clear link has been established between the two pathways. Here we report that cAMP-dependent protein kinase specifically inhibits G beta gamma-activated PLC-beta 2 activity but not that of the G alpha-activated PLC isoforms, and that the effect of PKA is not mimicked by PKC isozymes. Furthermore, we show that PKA directly phosphorylates serine residues of the PLC-beta 2 protein both in vivo and in vitro. Our results provide an insight into the specificity and nature of the crosstalk between the two G-protein-coupled signal transduction pathways.

Amino Acid Sequence↗
PubMed1996

Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids.

Oxidation of lipoproteins results in the formation of several polar phospholipids with pro-inflammatory and pro-atherogenic properties. To examine the possible role of lecithin/cholesterol acyltransferase (LCAT) in the metabolism of these oxidized phospholipids, we oxidized whole plasma with either Cu(2+) or a free-radical generator, and determined the various activities of LCAT. Oxidation caused a reduction in plasma phosphatidylcholine (PC), an increase in a short-chain polar PC (SCP-PC), and an inhibition of the transfer of long-chain acyl groups to cholesterol (LCAT activity) or to lyso PC (lysolecithin acyltransferase (LAT) I activity). However, the transfer of short-chain acyl groups from SCP-PC to lyso PCLAT II activity) was stimulated several fold, in direct correlation with the degree of oxidation. LAT II activity was not stimulated by oxidation in LCAT-deficient plasma, showing that it is carried out by LCAT. Oxidized normal plasma exhibited low LCAT activity even in the presence of exogenous proteoliposome substrate, indicating that the depletion of substrate PC was not responsible for the loss of activity. Oxidation of isolated LDL or HDL abolished their ability to support LCAT and LAT I activities of exogenous enzyme, but promoted the LAT II activity. Purified LCAT lost its LCAT and LAT I functions, but not its LAT II function, when oxidized in vitro. These results show that while oxidation of plasma causes a loss of LCAT's ability to transfer long-chain acyl groups, its ability to transfer short-chain acyl groups, from SCP-PC is retained, and even stimulated, suggesting that LCAT may have a physiological role in the metabolism of oxidized PC in plasma.

Adult↗
PubMed1996

Mechanical strain induces pp60src activation and translocation to cytoskeleton in fetal rat lung cells.

We have previously shown that mechanical strain-induced fetal rat lung cell proliferation is transduced via the phospholipase C-gamma-protein kinase C pathway. In the present study, we found that protein-tyrosine kinase activity of fetal lung cells increased after a short period of strain, which was accompanied by tyrosine phosphorylation of proteins of approximately 110-130 kDa. Several components of this complex were identified as pp60srcsubstrates. Strain increased pp60src activity in the cytoskeletal fraction, which coincided with a shift in subcellular distribution of pp60src from the Triton-soluble to the cytoskeletal fraction. Strain-induced pp60src translocation did not appear to be mediated via the focal adhesion kinase-paxillin pathway. In contrast, strain increased the association between pp60src and the actin filament-associated protein of 110 kDa. Preincubation of cells with herbimycin A, a tyrosine kinase inhibitor, abolished strain-induced phospholipase C-gamma1 tyrosine phosphorylation and its coimmunoprecipitation with pp60src. It also inhibited strain-induced DNA synthesis. These results suggest that activation of pp60src is an upstream event of the phospholipase C-gamma-protein kinase C pathway that may represent an important mechanism by which mechanical perturbations are converted to biological reactions in fetal lung cells.

Animals↗
PubMed1996

Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937.

The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, acting through its cognate nuclear receptor (vitamin D3 receptor, VDR) will induce myeloid leukemic cell lines to terminally differentiate into monocytes/macrophages. Because VDR acts by transcriptionally regulating responsive genes in a ligand-dependent manner, we sought target genes of the receptor that initiate, the differentiation process in response to ligand. We screened a cDNA library prepared from the myelomonocytic U937 cell line with probes generated from either 1,25-dihydroxyvitamin D3-treated or untreated cells. We report here that a candidate clone that hybridized differentially is the Cdk inhibitor p21WAF1, CIP1. Furthermore, we show that p21 is transcriptionally induced by 1,25-dihydroxyvitamin D3 in a VDR-dependent, but not p53-dependent, manner, and we identify a functional vitamin D response element in the p21 promoter. Transient overexpression of p21 and/or the related Cdk inhibitor p27 in U937 cells in the absence of 1,25-dihydroxyvitamin D3 results in the cell-surface expression of monocyte/macrophage-specific markers, suggesting that ligand-modulated transcriptional induction of the p21 gene facilitates the induced differentiation of this monoblastic cell line. We believe that this is the first report demonstrating that the ectopic overexpression of a Cdk inhibitor such as p21 or p27 directly leads to a terminal differentiation program.

Base Sequence↗
PubMed1996

Affinity electrophoretic determination of oligosaccharide specificity of Butea monosperma agglutinin.

The oligosaccharide specificity of newly isolated Butea monosperma agglutinin (BMA) was determined by two-dimensional lectin affinity electrophoresis of alpha-fetoprotein (AFP) with concanavalin A, lentil lectin, erythroagglutinating phytohemagglutinin and Allomyrina dichotoma lectin, of which the specificities to known AFP oligosaccharides had been established. Effects of neuraminidase treatment on the reactivities of AFP to the lectins were also studied. The results indicated that BMA had the highest affinity for the exposed Gal residues of nonreducing termini of biantennary complex-type oligosaccharides, and that the affinity was reduced to zero in the following order by the presence of monosialyl residue of the Man alpha1->3 arm, monosialyl residue of the Man alpha1->6 arm, monosialyl residue of the Man alpha 1->3 arm and bisecting G1cNAc, and disialyl residues. BMA did not recognize Neu5Ac alpha2->6 and Neu5Ac alpha2->3 substitutions of Gal. These characteristics of BMA were shown to be useful in identifying malignancy-associated alteration of AFP sugar chains.

Agglutinins↗
PubMed1996

Interaction of lectins with their ligand carbohydrate of alpha-fetoprotein: analysis by mixed-lectin affinity electrophoresis.

Serum or ascites alpha-fetoprotein (AFP) from patients with hepatocellular carcinoma and from a cord blood were analyzed by affinity electrophoresis with two lectins mixed in agarose gel in a combination of concanavalin A (Con A) and Lens culinaris agglutinin A (LCA-A) or of erythroagglutinating phytohemagglutinin (E-PHA) and Allomyrina dichotoma lectin (allo A). Con A- and LCA-A-reactive AFP-C2-L3 was not further retarded by mixing with either of the other lectin. It showed a mobility identical with that of AFP-C2 or AFP-L3. E-PHA- and allo A-reactive AFP-P4-A3 showed similar results. It migrated with intermediate mobilities of AFP-P4 and AFP-A3 depending on the concentrations of the two lectins mixed in the gel. The results indicate that the two mixed lectins compete with each other for the topologically different lectin-binding sites on the oligosaccharide of AFP molecule.

Carbohydrate Metabolism↗
PubMed1996

Application of structural concepts to evaluate the potential carcinogenicity of natural products.

The expert structure-activity relational system CASE/MULTICASE was used to obtain an assessment of the possible carcinogenicity of selligueain A, a plant-derived sweetener. Based upon a series of authoritative data bases it was predicted that this chemical had some marginal potential for being a 'non-genotoxic' rodent carcinogen. The relevance of this potential to possible human health risks is problematic. Still, given the fact that successful sweetener may be widely consumed, should this chemical be developed further, experimental determinations of its potential carcinogenicity appear in order.

Animals↗
PubMed1996

Capnography facilitates tight control of ventilation during transport.

OBJECTIVE: We tested the hypothesis that Paco2 would be more tightly controlled if end-tidal CO2 monitoring was used during hand ventilation for transport of intubated patients. DESIGN: Randomized, prospective analysis of the no-monitor and monitor-blind groups (the monitor was on the bed during transport but only the investigator was aware of the end-tidal CO2 values). Nonrandomized, prospective analysis of the monitor group (ventilation controlled using end-tidal CO2 value from monitor). SETTING: University hospital operating room and intensive care unit (ICU). PATIENTS: Fifty intubated patients who were transported from the operating room to the ICU or from the ICU to the neuroradiology suite were assigned randomly to one of two groups: a) no-monitor group (n = 25); and b) monitor-blind group (n = 25). An additional group (monitor group, n = 10) was subsequently added to the study. INTERVENTIONS: Capnography was instituted in all patients in a blocked fashion. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and end-tidal CO2 values were measured before and after transport. When comparing overall group data, pre- and post-Paco2 values were similar: monitor 39 +/- 2 vs. 41 +/- 2 torr (5.2 +/- 0.3 vs. 5.5 +/- 0.3 no-monitor 39 +/- 1 vs. 37 +/- torr (5.2 +/- 0.1 vs. 5.0 +/- 0.1 kPa). However, when comparing Paco2 values for individual patients, we found that there was significantly greater variability for Paco2 after transport when end-tidal CO2 was not used for control of ventilation during transport. CONCLUSIONS: These data do not support routine monitoring of end-tidal CO2 during short transport times in adult patients requiring mechanical ventilation. However, the monitor may prevent morbidity in patients requiring tight control of Paco2.

Adolescent↗
PubMed1996

Autonomic, electroencephalographic, and myogenic activity accompanying startle and its habituation during mid-childhood.

This study investigated (a) possible associations of the large individual variation in startle, with accompanying autonomic, central nervous system, and myogenic activities in a habituation paradigm; and (b) the patterns of habituation of these variables. Startle blinks to 40 noise bursts, heart rate, alpha activity, and orbicularis oculi electromyographic (EMG) activity preceding and following each startle response were measured in 40 normal 7-11-year-old boys. Startle amplitude and its habituation were independent of association with either initial values or successive changes in the autonomic, alpha, and EMG activities; whereas startle habituated, pre- and poststartle myogenic, alpha, and cardiac activities failed to habituate. Tonic cardiac activity was facilitated, suggesting sensitization of state, as proposed in the dual-process theory of habituation.

Autonomic Nervous System↗
PubMed1996

Mechanical strain induces constitutive and regulated secretion of glycosaminoglycans and proteoglycans in fetal lung cells.

We have previously shown that an intermittent strain regimen, which simulates fetal breathing movements, enhanced mixed fetal rat lung cell proliferation in organotypic culture. As glycosaminoglycans (GAGs) and proteoglycans (PGs) may modulate growth factor activities, we investigated the effect of intermittent strain on the formation and secretion of GAGs and PGs. Mechanical strain increased the incorporation of [3H]glucosamine and 35SO4 into GAGs and promoted the release of GAGs into the medium. The composition of the individual GAG molecules was not altered by strain. Mixed fetal lung cells subjected to strain secreted more [35S]biglycan into the medium than static controls but biglycan mRNA expression was not significantly altered. As mechanical strain primarily affected the secretion of GAGs and PGs, we then investigated which secretory pathways were stimulated by strain. Fetal lung cells secreted GAGs mainly through a constitutive (basal) pathway which was stimulated by strain. In contrast to static cultures, strain-induced constitutive secretion was partially blocked by the cytoskeletal disruptors colchicine and cytochalasin B, but not by the small G-protein inhibitors N-acetyl-S-farnesyl-L-cysteine and perillic acid. This result suggests that strain-induced constitutive export of GAGs depends on the functional integrity of the cytoskeleton. Strain also triggered the regulated secretion of GAGs. The strain-induced regulatory pathway in fetal lung cells was blocked by ionomycin, BAPTA/AM and gadolinium, suggesting that strain stimulated the regulatory pathway by inducing a rapid calcium influx via a stretch-activated ion channel. We conclude that mechanical strain of mixed fetal lung cells stimulates GAG and PG exocytosis via activation of both the regulated and constitutive pathways.

Animals↗
PubMed1996

Cigarette smoking and its risk factors among elementary school students in Beijing.

OBJECTIVES: This study investigated patterns of and risk factors for smoking among elementary school children in Beijing, China. METHODS: In 1988, anonymous questionnaires were administered to a multistage stratified cluster sample of 16996 students, aged mostly 10 to 12, in 479 fourth- to sixth-grade classes from 122 Beijing elementary schools. RESULTS: Approximately 28% of boys and 3% of girls had smoked cigarettes. The most frequently cited reasons for smoking initiation were "to imitate others' behavior" and "to see what it was like." Girls were more likely to get cigarettes from home than to purchase their own. Having close friends who smoked and being encouraged by close friends to smoke were strong risk factors for smoking. Smoking was also associated with lower parental socioeconomic status; having parents, siblings, or teachers who smoked; buying cigarettes for parents; performing poorly in school; and not believing that smoking is harmful to health. CONCLUSIONS: Gender differences in smoking prevalence among adolescents in China are larger than those among US teenagers, whereas the proximal risk factors for smoking are similar. Major efforts are needed to monitor and prevent smoking initiation among Chinese adolescents, particularly girls.

Adolescent↗
PubMed1996

Improved fluorometric quantification of urinary xanthurenic acid.

Measurement of urinary xanthurenic acid (XA) has been used clinically to study a variety of disorders caused by vitamin B6 deficiency. To obviate some cumbersome steps of current methods for measuring XA in human urine, we have developed a simple fluorometric method. We apply the urine sample to a solid-phase extraction column containing trimethylaminopropyl group bound to silica, which enables us to purify and concentrate the XA from the urine without contamination from various tryptophan metabolites. The XA in the acidic eluate can then be quantified fluorometrically. The linearity of the proposed method extends from 0.2 to 10.0 mg/L. The method is precise, yielding day-to-day CVs for two pooled control specimens (1.08 and 1.90 mg/L) of 1.2% and 2.6%, respectively. Correlation studies with an established HPLC method and with a spectrophotometric procedure showed correlation coefficients of 0.99 and 0.98, respectively. Interference from vitamin C, uric acid, salicylate, acetaminophen, vanillylmandelic acid, and homovanillic acid was insignificant. The proposed method for urinary XA is rapid, simple, and suitable for routine use in the clinical laboratory.

Chromatography, High Pressure Liquid↗