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Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 631 records · Page 35Linked to original sources
PubMed1999

IQGAP1 and calmodulin modulate E-cadherin function.

Ca(2+)-dependent cell-cell adhesion is mediated by the cadherin family of transmembrane proteins. Adhesion is achieved by homophilic interaction of the extracellular domains of cadherins on adjacent cells, with the cytoplasmic regions serving to couple the complex to the cytoskeleton. IQGAP1, a novel RasGAP-related protein that interacts with the cytoskeleton, binds to actin, members of the Rho family, and E-cadherin. Calmodulin binds to IQGAP1 and regulates its association with Cdc42 and actin. Here we demonstrate competition between calmodulin and E-cadherin for binding to IQGAP1 both in vitro and in a normal cellular milieu. Immunocytochemical analysis in MCF-7 (E-cadherin positive) and MDA-MB-231 (E-cadherin negative) epithelial cells revealed that E-cadherin is required for accumulation of IQGAP1 at cell-cell junctions. The cell-permeable calmodulin antagonist CGS9343B significantly increased IQGAP1 at areas of MCF-7 cell-cell contact, with a concomitant decrease in the amount of E-cadherin at cell-cell junctions. Analysis of E-cadherin function revealed that CGS9343B significantly decreased homophilic E-cadherin adhesion. On the basis of these data, we propose that disruption of the binding of calmodulin to IQGAP1 enhances the association of IQGAP1 with components of the cadherin-catenin complex at cell-cell junctions, resulting in impaired E-cadherin function.

Base Sequence↗
PubMed1999

Activation of

Reversible C(6)F(5) transfer takes place between the boron centers in the anion formed by methide abstraction from [MeZr{N(SiMe(3))(2)}(3)] or [Cp(2)ZrMe(2)] (L(n)M-CH(3) in the reaction scheme) by the perfluorinated diborane 1. The solution chemistry of the metallocenium ion pairs formed from 1 and [Cp(2)ZrMe(2)] is correlated with the observed ethylene polymerization behavior of 1 in comparison to the monoborane B(C(6)F(5))(3), the related diborane 1,2-C(6)H(4)[B(C(6)F(5))(2)](2), and the 9,10-diboraanthracene compound 9,10-(C(6)F(5))(2)C(12)B(2)F(8).

Journal Article↗
PubMed1999

Superhumps in a Peculiar SU Ursae Majoris-Type Dwarf Nova, ER Ursae Majoris.

We report the photometry of a peculiar SU Ursae Majoris-type dwarf nova, ER Ursae Majoris, for 10 nights during 1998 December and 1999 March, covering a complete rise to the supermaximum and a normal outburst cycle. Superhumps have been found during the rise to the superoutburst. A negative superhump appeared in the December 22 light curve, while the superhump on the next night became positive and had a large-amplitude waveform distinct from that of the previous night. In the normal outbursts we captured, superhumps with larger or smaller amplitudes seem to always exist, although it is not necessarily true for every normal outburst. These results show great resemblance to V1159 Ori. It is more likely that superhumps occasionally exist at essentially all phases of the eruption cycles of ER UMa stars, which should be considered in modeling.

Journal Article↗
PubMed1999

Intercalation of the (1S,2R,3S,4R)-N6-[1-(1,2,3,4-tetrahydro-2,3, 4-trihydroxybenz[a]anthracenyl)]-2'-deoxyadenosyl adduct in an oligodeoxynucleotide containing the human N-ras codon 61 sequence.

The (1S,2R,3S,4R)-N(6)-[1-(1,2,3,4-tetrahydro-2,3, 4-trihydroxybenz[a]anthracenyl)]-2'-deoxyadenosyl adduct at X6 of 5'-d(CGGACXAGAAG)-3'.5'-d(CTTCTTGTCCG)-3', incorporating codons 60, 61 (underlined), and 62 of the human N-ras protooncogene, results from trans opening of (1R,2S,3S,4R)-1,2-epoxy-1,2,3, 4-tetrahydrobenz[a]anthracenyl-3,4-diol by the exocyclic N6 of adenine. Two conformations of this adduct exist, in slow exchange on the NMR time scale. A structure for the major conformation, which represents approximately 80% of the population, is presented. In this conformation, an anti glycosidic torsion angle is observed for all nucleotides, including S,R,S,RA6. The refined structure is a right-handed duplex, with the benz[a]anthracene moiety intercalated on the 3'-face of the modified base pair, from the major groove. It is located between S,R,S,RA6.T17 and A7.T16. Intercalation is on the opposite face of the modified S,R,S,RA6.T17 base pair as compared to the (1R,2S,3R,4S)-N6-[1-(1,2,3,4-tetrahydro-2, 3,4-trihydroxybenz[a]anthracenyl)]-2'-deoxyadenosyl adduct, which intercalated 5' to the modified R,S,R,SA6.T17 base pair [Li, Z. , Mao, H., Kim, H.-Y., Tamura, P. J., Harris, C. M., Harris, T. M., and Stone, M. P. (1999) Biochemistry 38, 2969-2981]. The spectroscopic data do not allow refinement of the minor conformation, but suggest that the adenyl moiety in the modified nucleoti111S,R, S,RA6 adopts a syn glycosidic torsion angle. Thus, the minor conformation may create greater distortion of the DNA duplex. The results are discussed in the context of site-specific mutagenesis studies which reveal that the S,R,S,RA6 lesion is less mutagenic than the R,S,R,SA6 lesion.

Adenine↗
PubMed1999

Activation of regulatory cells suppresses experimental allergic encephalomyelitis via secretion of IL-10.

Suppression of CD4+ Th1 cell-mediated autoimmune disease via immune deviation is an attractive potential therapeutic approach. CD4+ Th2 T cells specific for myelin basic protein, induced by immunization of young adult male SJL mice, suppress or modify the progression of CNS autoimmune disease. This report demonstrates that activation of non-neuroantigen-specific Th2 cells is sufficient to suppress both clinical and histological experimental allergic encephalomyelitis (EAE). Th2 cells were obtained following immunization of male SJL mice with keyhole limpet hemocyanin. Transfer of these cells did not modify EAE, a model of human multiple sclerosis, in the absence of cognate Ag. Disease suppression was obtained following adoptive transfer and subcutaneous immunization. Suppression was not due to the deletion of myelin basic protein-specific T cells, but resulted from the presence of IL-10 as demonstrated by the inhibition of Th2-mediated EAE suppression via passive transfer with either anti-IL-10 or anti-IL-10R mAb. These data demonstrate that peripheral activation of a CD4+ Th2 population specific for an Ag not expressed in the CNS modifies CNS autoimmune disease via IL-10. These data suggest that either peripheral activation or direct administration of IL-10 may be of benefit in treating Th1-mediated autoimmune diseases.

Adoptive Transfer↗
PubMed1999

The cytoplasmic domain of the platelet glycoprotein Ibalpha is phosphorylated at serine 609.

The alpha chain of the platelet von Willebrand factor receptor, glycoprotein (GP) Ib, is not known to be phosphorylated. Here, we report that the cytoplasmic domain of GPIbalpha is phosphorylated at Ser(609); this was detected by immunoblotting with an anti-phosphopeptide antibody, anti-pS609, that specifically recognizes the GPIbalpha C-terminal sequence S(606)GHSL(610) only when Ser(609) is phosphorylated. Immunoabsorption with anti-pS609 removed almost all of the GPIbalpha from platelet lysates, indicating a high proportion of GPIbalpha phosphorylation. Anti-pS609 inhibited GPIb-IX binding to the intracellular signaling molecule, 14-3-3zeta. Dephosphorylation of GPIb-IX with potato acid phosphatase inhibited anti-pS609 binding and also 14-3-3zeta binding. A synthetic phosphopeptide corresponding to the GPIbalpha C-terminal sequence (SIRYSGHpSL), but not a nonphosphorylated identical peptide, abolished GPIb-IX binding to 14-3-3zeta. Thus, phosphorylation at Ser(609) of GPIbalpha is important for 14-3-3zeta binding to GPIb-IX. In certain regions of spreading platelets, particularly at the periphery, there was a reduction in GPIbalpha staining by anti-pS609 as observed under a confocal microscope, indicating that a subpopulation of GPIbalpha molecules in these regions is dephosphorylated. These data suggest that phosphorylation and dephosphorylation at Ser(609) of GPIbalpha regulates GPIb-IX interaction with 14-3-3 and may play important roles in the process of platelet adhesion and spreading.

14-3-3 Proteins↗
PubMed1999

Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

BACKGROUND AND METHODS: Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. RESULTS: Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). CONCLUSIONS: Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

Adult↗
PubMed1999

Role of a polycyclic aromatic hydrocarbon bay region ring in modulating DNA adduct structure: the non-bay region (8S,9R,10S, 11R)-N(6)-[11-(8,9,10,11-tetrahydro-8,9, 10-trihydroxybenz[a]anthracenyl)]-2'-deoxyadenosyl adduct in codon 61 of the human N-ras protooncogene.

The structure of the non-bay region (8S,9R,10S,11R)-N(6)-[11-(8,9,10, 11-tetrahydro-8,9,10-trihydroxybenz[a]anthracenyl)]-2'-de oxyadenosyl adduct at X(6) of 5'-d(CGGACXAGAAG)-3'.5'-d(CTTCTTGTCCG)-3', incorporating codons 60, 61 (underlined), and 62 of the human N-ras protooncogene, was determined. Molecular dynamics simulations were restrained by 475 NOEs from (1)H NMR. The benz[a]anthracene moiety intercalated above the 5'-face of the modified base pair and from the major groove. The duplex suffered distortion at and immediately adjacent to the adduct site. This was evidenced by the disruption of the Watson-Crick base pairing for X(6) x T(17) and A(7) x T(16) and the increased rise of 7.7 A between base pairs C(5) x G(18) and X(6) x T(17). Increased disorder was observed as excess line width of proton resonances near the lesion site. Comparison with the bay region benzo[a]pyrene [Zegar, I. S., Kim, S. J., Johansen, T. N., Horton, P. J., Harris, C. M., Harris, T. M., and Stone, M. P. (1996) Biochemistry 35, 6212-6224] and bay region benz[a]anthracene [Li, Z., Mao, H., Kim, H.-Y., Tamura, P. J., Harris, C. M., Harris, T. M., and Stone, M. P. (1999) Biochemistry 38, 2969-2981] adducts with the corresponding stereochemistry and at the same site shows that this non-bay region benz[a]anthracene lesion assumes different base pair geometry, in addition to exhibiting greater disorder. These differences are attributed to the loss of the bay region ring. The results suggest the bay region ring contributes to base stacking interactions at the lesion site. These structural differences between the non-bay and bay region lesions are correlated with site-specific mutagenesis data. The bay region benzo[a]pyrene and bay region benz[a]anthracene adducts were poorly replicated in vivo, and induced A --> G mutations. In contrast, the non-bay region benz[a]anthracene adduct was easily bypassed in vivo and was nonmutagenic.

Bay-Region, Polycyclic Aromatic Hydrocarbon↗
PubMed1999

Silencing of metallothionein-I gene in mouse lymphosarcoma cells by methylation.

Metallothionein-I (MT-I) gene is silenced by methylation of CpG islands in mouse lymphosarcoma P1798 cells but not in the thymus, the cell type from which the tumor was derived. Bisulfite genomic sequencing revealed that all 21 CpG dinucleotides present within -216 bp to +1 bp with respect to transcription start site are methylated in the tumor cell line, but none is methylated in the thymus. The lymphosarcoma cells induced MT-I in response to heavy metals only after demethylation with 5-azacytidine (5-AsaC). The electrophoretic mobility shift assay using specific oligonucleotide probes showed that the key transcription factors regulating MT-I gene (e.g., MTF-1, Sp 1 and MLTF/USF) are active in P1798 cells. In vivo footprinting of the proximal promoter region showed that none of the metal regulatory elements (MREs) or MLTF/USF are occupied in response to heavy metals. Demethylation of the lymphosarcoma cells with 5-AzaC resulted in constitutive footprinting at MLTF/ARE, and zinc-inducible footprinting at MRE-c, MRE-d and MRE-e sites. Demethylation of just 10-20% of the CpG islands was sufficient to render the gene inducible by cadmium or zinc. The MT-I induction persisted in the cancer cells for several generations even after withdrawal of 5-AzaC from the culture medium.

Animals↗
PubMed1999

Transcriptional induction of metallothionein-I and -II genes in the livers of Cu,Zn-superoxide dismutase knockout mice.

The levels of metallothionein-I and -II (MT-I and MT-II) mRNAs were elevated (10- to 12-fold), specifically in the livers of mice with homozygous deletion of the gene for Cu,Zn-SOD (Sod1-/-), the enzyme that catalyzes the removal of O(-)(2). The induction of MT mRNA occurred primarily at the level of transcription. In vivo genomic footprinting of the MT-I promoter region revealed distinctive footprinting at MRE-d, MRE-c, and MLTF/ARE sites in the livers of knockout mice. MTF-1, the key factor responsible for the heavy-metal and oxidative stress-induced expression of the MT-I gene, was activated 3-fold in the nuclear extract from the livers of Cu,Zn-SOD null mice. Because metallothioneins are potent scavengers of reactive oxygen species and protect cells from oxidative stress, the apparent normal characteristics of the mice with the disrupted Cu, Zn-SOD gene are probably due to overexpression of MT-I and MT-II in the livers of these animals.

Animals↗
PubMed1999

Involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and p53 in neuronal apoptosis: evidence that GAPDH is upregulated by p53.

We recently reported that cytosine arabinoside (AraC)-induced apoptosis of cerebellar neurons involves the overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The present study was undertaken to investigate whether p53 and/or Bax overexpression participates in the AraC-induced apoptosis of cerebellar granule cells and, if so, the relationship between p53 induction and GAPDH overexpression in these cells. AraC-induced apoptosis of cerebellar granule cells was preceded by an increase in levels of p53 mRNA and protein detected between 1 and 8 hr after treatment. The mRNA level for a p53 target gene, Bax, was also increased. The increase in GAPDH mRNA lasted longer than that of either p53 or Bax, and the level of GAPDH protein in the particulate fraction increased after induction of GAPDH mRNA. The antisense oligonucleotide to p53 protected granule cells from AraC-induced chromatin condensation, internucleosomal cleavage, and apoptotic death. The inhibition of p53 expression by the p53 antisense oligonucleotide not only blocked the expression of Bax but also partially suppressed the increased GAPDH mRNA and protein levels. Conversely, the suppression of GAPDH expression and subsequent attenuation of apoptosis of granule cells by GAPDH antisense oligonucleotide did not influence the expression of p53 or Bax. Cerebellar granule cells prepared from p53 knock-out mice were resistant to AraC toxicity, and the p53 gene knock-out suppressed AraC-upregulated GAPDH expression. Moreover, infection of PC12 cells with an adenoviral vector containing p53 gene dramatically increased GAPDH expression and triggered cell apoptosis. These results suggest that AraC-induced apoptosis of cerebellar granule cells involves the expression of both GAPDH and p53 and that, similar to Bax, GAPDH is upregulated by p53 after exposure to the apoptotic insult.

Animals↗
PubMed1999

Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice.

gamma-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic transmission and have been implicated in responses to sedative/hypnotic agents (including neuroactive steroids), anxiety, and learning and memory. Using gene targeting technology, we generated a strain of mice deficient in the delta subunit of the GABA type A receptors. In vivo testing of various behavioral responses revealed a strikingly selective attenuation of responses to neuroactive steroids, but not to other modulatory drugs. Electrophysiological recordings from hippocampal slices revealed a significantly faster miniature inhibitory postsynaptic current decay time in null mice, with no change in miniature inhibitory postsynaptic current amplitude or frequency. Learning and memory assessed with fear conditioning were normal. These results begin to illuminate the novel contributions of the delta subunit to GABA pharmacology and sedative/hypnotic responses and behavior and provide insights into the physiology of neurosteroids.

Animals↗
PubMed1999

Involvement of peripheral NMDA and non-NMDA receptors in development of persistent firing of spinal wide-dynamic-range neurons induced by subcutaneous bee venom injection in the cat.

To study the roles of peripheral excitatory amino acids receptor subtypes N-methyl-D-aspartate (NMDA) and non-NMDA receptors in persistent nociception, extracellular single unit recording technique was used to assess the effects of a single dose NMDA and non-NMDA receptor antagonists, AP(5) (5-aminophosphonovaleric acid) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or DNQX (6,7-dinitroquinoxaline-2,3-dione), on s.c. bee venom-induced increase in firing of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of the urethane-chloralose anesthetized cats. Subcutaneous bee venom injection into the cutaneous receptive field resulted in a single phase of increased firing of WDR neurons over the background activity for more than 1 h. Local pre-administration of AP(5) (200 microg/100 microl) or CNQX (8.3 microg/100 microl) into the bee venom injection site produced 94% (1.01+/-0.96 spikes/s, n=5) or 76% (2.97+/-0.58 spikes/s, n=4) suppression of the increased neuronal firing when compared with local saline (16.32+/-4.55 spikes/s, n=10) or dimethyl sulfoxide (DMSO) (12.37+/-6.36 spikes/s, n=4) pre-treated group, respectively. Local post-administration of the same dose of AP(5) produced a similar result to the pre-treatment group with a 67% inhibition of the mean firing rate, however, the same treatment with CNQX and even a higher dose of DNQX (100 microg/100 microl) did not produce any inhibition of the neuronal firing induced by s.c. bee venom injection (DNQX vs. DMSO: 23.91+/-0. 25 vs. 22.14+/-0.04 spikes/s, P=0.0298, n=5). In the control experiments, local pre-administration of the same dose of AP(5) or CNQX into a region on the contralateral hindpaw symmetrical to the bee venom injection site produced no significant influence on the increased firing of the WDR neurons [contralateral AP(5) vs. saline: 14.17+/-6.27 spikes/s (n=5) vs. 16.32+/-4.55 spikes/s (n=10), P0.05; contralateral CNQX vs. DMSO: 12.85+/-6.38 spikes/s (n=4) vs. 12. 37+/-6.36 spikes/s (n=4), P0.05], implicating that the suppressive action of local AP(5) or CNQX was not the result of systemic effects. The present results suggest that activation of the peripheral NMDA receptors is involved in both induction and maintenance, while activation of non-NMDA receptors is only involved in induction, but not in the maintenance of persistent firing of the dorsal horn WDR neurons induced by s.c. bee venom injection.

2-Amino-5-phosphonovalerate↗
PubMed1999

Identification of seven serotypes of bluetongue virus from the People's Republic of China.

Seven serotypes (1, 2, 3, 4, 12, 15 and 16) of bluetongue virus were isolated from the blood of sheep and cattle in the People's Republic of China between 1986 and 1996. Six of these viruses were isolated in Yunnan province. The sheep from which serotypes 1 and 16 were isolated showed obvious signs of bluetongue disease, whereas the cattle from which serotypes 2, 3, 4, 12 and 15 were isolated were clinically normal. Phylogenetic analyses of these viruses indicate that they are more closely related to one another, and to an Australian strain of serotype 1, than they are to prototype strains of bluetongue virus serotypes 2, 10, 11, 13 and 17 from the USA.

Animals↗
PubMed1999

Spectral properties of Trp182, Trp194, and Trp250 on the alpha subunit of bacterial luciferase.

The phosphorescence and fluorescence properties of bacterial luciferase (alphabeta) mutants from Xenorhabdus luminescens were investigated. All tryptophans in the alpha and beta subunits were replaced with tyrosines except for one or two tryptophans in the alpha subunit. Because one luciferase mutant (W250) retained only a single tryptophan in the alpha subunit while two other mutants (W182/250 and W194/250) each contained two tryptophans in the alpha subunit, it was possible to deduce the spectral properties of these specific tryptophans (Trp182, Trp194, Trp250). Analyses of the phosphorescence properties were particularly revealing as only a single phosphorescence emission peak at 411-414 nm was observed for the W250 and W194/250 mutants while peaks at 409 and 414 nm could be clearly observed for the W182/250 mutant. Coupled with intrinsic fluorescence quenching experiments, these results show that alphaTrp182 is in a distinctly polar environment while alphaTrp250 is in a hydrophobic region and illustrate the advantages of using phosphorescence to recognize different microenvironments for tryptophan residues.

Amino Acid Substitution↗
PubMed1999

Structural and Thermodynamic Properties of Solutions of Butane in Aqueous Sodium Dodecyl Sulfate: A Study Using Neutron Scattering and Solubility Measurements.

The solubility of n-butane at a pressure of 1.013 bar in aqueous solutions of sodium dodecyl sulfate (SDS) has been measured over a range of concentration from below the critical micelle concentration (CMC) at about 8 mol kg(-1) to about 90 mol kg(-1) at three different temperatures. The free energy, enthalpy, and entropy of transfer of butane from water to the micelle were respectively -19.0 kJ mol(-1), 5.5 kJ mol(-1), and 80 J K(-1) mol(-1). At 68 mol kg(-1) a transition was found with a free energy of about -400 J mol(-1). Small-angle neutron experiments were used to study the effect of butane on the state of aggregation of the SDS. For each butane molecule incorporated into a micelle, the aggregation number of the SDS increased by an average of about 1.4 molecules. Thus, at 1.013 bar of butane and 50 mM SDS, where the solubility is about 1 butane to 10 SDS, the average micelle increases in size by about 20%, most of which comes from the additional SDS molecules. The aggregation behavior is qualitatively similar to that reported for hexane, heptane, and octane, but the effect seems to be larger for butane for a given volume of solute hydrocarbon. Small-angle scattering did not observe any substantial change in structure across the phase transition at 68 mol kg(-1). Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Analysis of beta-N-oxalyl-L-alpha,beta-diaminopropionic acid and homoarginine in Lathyrus sativus by capillary zone electrophoresis.

A simple capillary zone electrophoresis (CZE) method has been developed for the simultaneous quantitative determination of beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (beta-ODAP) and homoarginine in Lathyrus sativus (LS; grass pea). A new Na2B4O7-Na2SO4 run buffer was used and the pH was 9.20, contents of beta-ODAP and homoarginine in crude extracts of LS plant material were determined with this method, the RSDs of peak areas of beta-ODAP and homoarginine were 2.62% and 3.61%, respectively. It was found that the equilibrium concentration ratio of alpha- and beta-ODAP decreased from 34.5/65.5 to 28.6/71.4 when the pH of the solution increased from pH 3.0 to pH 11.0.

Amino Acids, Diamino↗