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Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 181 records · Page 10Linked to original sources
PubMed2001

Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition induced by novel K vitamin analogs.

We previously found that K vitamin analogues caused cell growth inhibition in Hep3B hepatoma cells in vitro, which was associated with their inhibitory effects on protein tyrosine-phosphatases. In this study, we show that Cdc25A, a protein phosphatase, was inactivated by novel arylating K vitamin analogues. The inactivation of Cdc25A correlated with their effects on cell growth inhibition. Cyclin-dependent kinase (Cdk) 4, an important regulator for G(1) progression, was found to be tyrosine-phosphorylated by the arylating analogues, and this phosphorylation was correlated with the inhibitory effects of the analogues on Cdc25A activity. Furthermore, Cdk4 dephosphorylation experiments showed that Compound (Cpd) 5, a prototype arylating analogue, inhibited Cdc25A-mediated Cdk4 dephosphorylation, whereas Cpd 26, a nonarylating vitamin K analogue, had no effect on this event. We also examined Cdk4 kinase activity using retinoblastoma protein as a substrate and found that Cpd 5 inhibited retinoblastoma protein phosphorylation in a concentration-dependent manner, indicating that Cdk4 activity was inhibited by Cpd 5 treatment. Moreover, the thiol-antioxidants glutathione and N-acetyl-L-cysteine antagonized the Cpd 5-induced Cdk4 tyrosine phosphorylation, whereas the nonthiol-antioxidants catalase and superoxide dismutase did not. These results suggest that Hep3B cell growth inhibition by these K vitamin analogues may be related in part to inactivation of Cdc25A activity and support the hypothesis that Cdc25A is an attractive target for drugs designed to inhibit cancer cell growth.

Acetylcysteine↗
PubMed2001

Microscopic electronic inhomogeneity in the high-Tc superconductor Bi2Sr2CaCu2O8+x.

The parent compounds of the copper oxide high-transition-temperature (high-Tc) superconductors are unusual insulators (so-called Mott insulators). Superconductivity arises when they are 'doped' away from stoichiometry. For the compound Bi2Sr2CaCu2O8+x, doping is achieved by adding extra oxygen atoms, which introduce positive charge carriers ('holes') into the CuO2 planes where the superconductivity is believed to originate. Aside from providing the charge carriers, the role of the oxygen dopants is not well understood, nor is it clear how the charge carriers are distributed on the planes. Many models of high-Tc superconductivity accordingly assume that the introduced carriers are distributed uniformly, leading to an electronically homogeneous system as in ordinary metals. Here we report the presence of an electronic inhomogeneity in Bi2Sr2CaCu2O8+x, on the basis of observations using scanning tunnelling microscopy and spectroscopy. The inhomogeneity is manifested as spatial variations in both the local density of states spectrum and the superconducting energy gap. These variations are correlated spatially and vary on the surprisingly short length scale of approximately 14 A. Our analysis suggests that this inhomogeneity is a consequence of proximity to a Mott insulator resulting in poor screening of the charge potentials associated with the oxygen ions left in the BiO plane after doping, and is indicative of the local nature of the superconducting state.

Journal Article↗
PubMed2001

High fat diet increases the weight of rat ventral prostate.

BACKGROUND: Understanding the mechanisms by which diet influences the prostate may eventually lead to novel approaches for preventing prostate cancer. The objective of this research is to examine the impact of dietary fat, vitamin D, and genistein on prostate weight, serum and intraprostatic androgen levels, and the expression of several androgen-response genes. METHODS: Sprague-Dawley rats were fed, beginning at 21 days of age, for 1 or 3 months of experimental diets with high saturated fat (32.2% calories from fat), low saturated fat (3.6% calories from fat), genistein plus (20 mg/kg), genistein deficient, vitamin D surplus (4,000 U/kg), or vitamin D deficient. The body weight, food intake, the weights of the ventral prostate and dorsolateral prostate, and the levels of testosterone and dihydrotestosterone (DHT) in the serum and in the prostate were determined. The expression of androgen-response genes was characterized by Northern blot analysis. RESULTS: The pilot experiments showed that high dietary fat appeared to consistently increase the weight of the ventral prostate, while vitamin D or genistein did not have a consistent effect on prostate weight. Further analysis confirmed that the ventral prostate is 15% (P < 0.001) heavier in the rat on a high fat diet as compared to a low fat diet. Dietary fat had no significant influence on the levels of serum and intraprostatic androgens and the expression of androgen-response genes. CONCLUSIONS: Our results suggested that the ventral prostate weight of the rat is increased without affecting the androgen axis by feeding the animals with high fat diet beginning at 21 days of age. This observation is potentially important since epidemiological data suggest that saturated fat consumption is a major risk factor associated with prostate cancer incidence rate.

Androgens↗
PubMed2001

Cell signaling pathways mediating epidermal growth factor stimulation of Na:K:2Cl cotransport activity in rabbit corneal epithelial cells.

We characterized the signaling and ion transport pathways that mediate epidermal growth factor receptor physiological control in SV40-immortalized rabbit corneal epithelial cells (tRCEC). Our evaluation employed single-cell fluorescence imaging to measure the intracellular [Na+]i in these cells loaded with the Na+ sensitive dye, SBFI. EGF (1 to 5 ng/ml) transiently increased [Na+]i from 10 mm to as much as 35 mm after 25 min, which was followed by a decline towards its control value. These increases waned at higher EGF concentrations up to 50 ng/ml. Both inhibition of EGF receptor-linked tyrosine kinase activity (50 microm RG-13022) and cPLA2 activity (10 microm AACOCF3) obviated EGF-induced increases in [Na+]i. In contrast, PGE2 (10 microg/ml) and cAMP (2 mm) increased [Na+]i by 25 mm. Inhibition of NKCC activity through exposure to either Cl-free Ringers or 300 microm furosemide in NaCl Ringers eliminated EGF-induced increases in [Na+]i. Similarly, EGF failed to increase [Na+]i following inhibition of: 1) PKA activity (10 microm H-89); 2) Erk1/2 (15 microm PD98059) or 3) p38 (15 microm SB203580) activity. Stimulation protein kinase C activity (0.1 microm PMA) transiently increased [Na+]i followed by a decline towards its baseline value. EGF-induced increases in [Na+]i were unaltered by inhibition of K+ conductance (100 microm 4-AP). Taken together, EGF stimulates Erk1/2; p38 and cPLA2 activity. Their stimulation increases PGE2 and cAMP levels resulting in PKA and NKCC activation.

Animals↗
PubMed2001

Artificial aging of phenanthrene in porous silicas using supercritical carbon dioxide.

Expedited artificial aging is described and demonstrated using a novel system that circulates a solution of supercritical carbon dioxide and a hydrophobic organic sorbate (phenanthrene) through a closed loop containing a porous substrate. Unlike traditional methods used to simulate the natural aging process, our approach allows for real-time monitoring of sorption equilibria, and the process is highly accelerated due to the unique physical properties of supercritcal carbon dioxide. The effectiveness of the system to simulate aging was demonstrated with a series of experiments in which three silicas with varying particle and pore sizes were loaded with phenanthrene. Batch aqueous desorption experiments were used to evaluate the extent of the aging process. For the two types of particles containing the largest pores (i.e., mean diameters of 202 and 66 A), 95% and 86%, respectively, of the phenanthrene was released to the aqueous fraction within 3 h. In contrast, only 16% of the phenanthrene was released from particles having a mean pore diameter of 21 A after 24 h. These results were confirmed by the results from an aqueous column desorption experiment. Confounding factors that might contribute to slow aqueous desorption such as the hydration state of the particles' surfaces, the chemical form of the loaded phenanthrene, and the organic carbon content were investigated and/or normalized for all three particle types. Consequently, we were able to attribute the slow desorption behavior and the presence of the resistant fraction in the 21 A silica to pore effects. With properly designed experiments, the results of this study suggest that the supercritical fluid system could be extended to the study of contaminant aging and bioavailability in natural soils and sediments.

Adsorption↗
PubMed2001

Cancer incidence in New York State acquired immunodeficiency syndrome patients.

To identify cancers that occur at higher rates in acquired immunodeficiency syndrome (AIDS) patients, the cancer experience of New York State (NYS) AIDS patients aged 15-69 years who were diagnosed between 1981 and 1994 was compared with that of the NYS general population. Sex and HIV risk group-specific standardized incidence ratios (SIRs), post-AIDS relative risks, and trends of relative risks were calculated to determine cancer risk. Among non-AIDS-related cancers, elevated SIRs were found for Hodgkin's disease (male, 8.0; female, 6.4; heterosexually infected males, 31.3); cancer of the rectum, rectosigmoid, and anus (male, 3.3; female, 3.0); trachea, bronchus, and lung (male, 3.3; female, 7.5); and brain and central nervous system (male, 3.1; female, 3.4; heterosexually infected females, 23.8) cancers. Moreover, significant trends of increasing relative risks from the pre-AIDS to the post-AIDS period were found for cancers of the rectum, rectosigmoid, and anus; trachea, bronchus, and lung; skin; and connective tissues (all sites, p < 0.05) among males. For AIDS-related cancers in women, invasive cervical cancer had an overall SIR of 9.1 (95% confidence interval: 6.9, 10.8) and a post-AIDS relative risk of 6.5 (95% confidence interval: 4.1, 9.7). This population-based registry linkage analysis evaluates cancer risk in AIDS patients by sex and risk factors and adds evidence that HIV-associated immunosuppression increases the risks of specific types of cancer.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Zinc diphosphonates templated by organic amines: syntheses and characterizations of [NH3(CH2)2NH3]Zn(hedpH2)2*2H2O and [NH3(CH2)nNH3(CH2)nNH3]Zn2(hedpH)2*2H2O (n=4,5,6) (hedp=1-hydroxyethylidenediphophonate).

Four new zinc diphosphonate compounds with formulas [NH(3)(CH(2))(2)NH(3)]Zn(hedpH(2))(2).2H(2)O, 1, [NH(3)(CH(2))(n)()NH(3)]Zn(2)(hedpH)(2).2H(2)O, (n = 4, 2; n = 5, 3; n = 6, 4) (hedp = 1-hydroxyethylidenediphosphonate) have been synthesized under hydrothermal conditions at 110 degrees C and in the presence of alkylenediamines NH(2)(CH(2))(n)()NH(2) (n = 2, 4, 5, 6). Crystallographic data for 1: monoclinic, space group C2/c, a = 24.7422(15), b = 5.2889(2), c = 16.0338(2) A, beta = 117.903(1) degrees, V = 1856.17(18) A(3), Z = 4; 2: monoclinic, space group P2(1)/n, a = 5.4970(3), b = 12.1041(6), c = 16.2814(12) A, beta = 98.619(5) degrees, V = 1071.07(11) A(3), Z = 2; 3: monoclinic, space group P2(1)/n, a = 5.5251(2), b = 12.5968(3), c = 16.1705(5) A, beta = 99.182(1) degrees, V = 1111.02(6) A(3), Z = 2; 4: triclinic, space group P-1, a = 5.4785(2), b = 14.1940(5), c = 16.0682(6) A, alpha = 81.982(2) degrees, beta = 89.435(2) degrees, gamma = 79.679(2) degrees, V = 1217.11(8) A(3), Z = 2. In compound 1, two of the phosphonate oxygens are protonated. The metal ions are bridged by the hedpH(2)(2-) groups through three of the remaining four phosphonate oxygens, forming a one-dimensional infinite chain. The protonated ethylenediamines locate between the chains in the lattice. In compounds 2-4, only one phosphonate oxygen is protonated. Compounds 2 and 3 have a similar three-dimensional open-network structure composed of [Zn(2)(hedpH)(2)](n) double chains with strong hydrogen bonding interactions between them, thus generating channels along the [100] direction. The protonated diamines and water molecules reside in the channels. Compound 4 contains two types of [Zn(2)(hedpH)(2)](n) double chains which are held together by strong hydrogen bonds, forming a two-dimensional network. The interlayer spaces are occupied by the [NH(3)(CH(2))(6)NH(3)](2+) cations and water molecules. The significant difference between structures 2-4 is also featured by the coordination geometries of the zinc atoms. The geometries of those in 2 can be described as distorted octahedral, and those in 3 as distorted square pyramidal. In 4, two independent zinc atoms are found, each with a distorted octahedral and a tetrahedral geometry, respectively.

Journal Article↗
PubMed2001

MEK1/2 inhibitors promote Ara-C-induced apoptosis but not loss of Deltapsi(m) in HL-60 cells.

The effects of pharmacologic MEK1/2 inhibitors on ara-C-mediated mitochondrial injury, caspase activation, and apoptosis have been examined in HL-60 leukemic cells. Coadministration of subtoxic concentrations of the MEK1/2 inhibitors U0126 (20 microM), PD98059 (40 microM), or PD184352 (10 microM) with 10-100 microM ara-C (6 h) potentiated apoptosis (i.e., by approx twofold), and pro-caspase 3, pro-caspase 8, Bid, and PARP cleavage. Unexpectedly, MEK1/2 inhibitors failed to enhance ara-C-mediated loss of mitochondrial membrane potential (DeltaPsi(m)), but instead induced substantial increases in cytosolic release of cytochrome c and Smac/DIABLO. U0126/ara-C-mediated apoptosis and pro-caspase 3 activation, but not cytochrome c or Smac/DIABLO release, were blocked by the pan-caspase inhibitor ZVAD-fmk. Together, these findings indicate that potentiation of ara-C-mediated lethality in HL-60 cells by MEK1/2 inhibitors involves enhanced cytosolic release of cytochrome c and Smac/DIABLO but not discharge of DeltaPsi(m), implicating activation of an apoptotic pathway that differs, at least with respect to the nature of the accompanying mitochondrial injury, from that triggered by ara-C alone.

Apoptosis↗
PubMed2001

RNA interference of a trypanosome topoisomerase II causes progressive loss of mitochondrial DNA.

We studied the function of a Trypanosoma brucei topoisomerase II using RNA interference (RNAi). Expression of a topoisomerase II double-stranded RNA as a stem-loop caused specific degradation of mRNA followed by loss of protein. After 6 days of RNAi, the parasites' growth rate declined and the cells subsequently died. The most striking phenotype upon induction of RNAi was the loss of kinetoplast DNA (kDNA), the cell's catenated mitochondrial DNA network. The loss of kDNA was preceded by gradual shrinkage of the network and accumulation of gapped free minicircle replication intermediates. These facts, together with the localization of the enzyme in two antipodal sites flanking the kDNA, show that a function of this topoisomerase II is to attach free minicircles to the network periphery following their replication.

Animals↗
PubMed2001

Multifunctionalized alpha,beta-cyclopentenones from C-2 and C-4-ulopyranosyl compounds: a stereospecific rearrangement initiated by base.

Base treatment of O-benzyl protected C-2- or C-4-ulopyranosyl compounds (4 alpha, 4 beta, and 11) by either 10% Et(3)N or 1% K(2)CO(3) in MeOH initiated a beta elimination to afford alpha,beta-unsaturated C-ulopyranosyl compounds (5 alpha, 5 beta, and 12), which further rearranged in a stereocontrolled manner to multifuctionalized alpha,beta-cyclopentenones (6 and 14) in 70-80% yield. Both C-alpha- and C-beta-2-ulosides (5 alpha and 5 beta) produced the same cyclopentenone 6, indicating that a 1,2-enolate is formed prior to the cleavage of the C-5--O bond. Because 6 is racemic, it was probably formed by the intramolecular cycloaldolization of two equally populated enantiomeric intermediates. When treated with 90% Et(3)N in MeOH, 5 alpha yielded almost exclusively 15 (isomer of 6), which was formed by a migration of the double bond in 5 alpha during the previously described rearrangement. Thus either 6 or 15 was the major product, depending on the base used.

Cyclopentanes↗
PubMed2001

Different subtypes of alpha1-adrenoceptor modulate different K+ currents via different signaling pathways in canine ventricular myocytes.

Multiple subtypes (alpha1A, alpha1B, and alpha1D) of alpha1-adrenoreceptors (alpha1ARs) co-exist in the heart and mediate a variety of cellular functions. We studied alphaAR modulation of inward rectifier (IK1) and transient outward (Ito) K(+) currents in canine ventricular myocytes. Phenylephrine at 10 microM depressed only Ito without affecting IK1 and at 100 microM inhibited both Ito and IK1. The effect of phenylephrine on Ito was abolished by (+)niguldipine (10 nm) to inhibit alpha1AARs but not by chloroethyclonidine (10 microM) to inactivate alpha1BARs nor by BMY-7378 to antagonize alpha1DARs. In contrast, phenylephrine inhibition of IK1 was reversed only by BMY-7378 (1 nm). PDD (100 nm, phorbol ester activator of protein kinase C (PKC)) simulates and bisindolylmaleimide (50 nm, PKC inhibitor) weakens phenylephrine modulation of Ito but not IK1. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 and inhibitor peptides abolished the effects of phenylephrine on IK1. Enhancement of PKC or CaMKII activities was seen in alpha1aAR- or alpha1dAR-transfected HEK293 cells and in myocytes pretreated with 10 or 100 microM phenylephrine, respectively. Our data suggest that different subtypes of alpha1ARs selectively modulate different cardiac K(+) currents via different signal transduction mechanisms; alpha1AARs mediate Ito regulation via PKC, and alpha1DARs mediate IK1 regulation via CaMKII.

Adrenergic alpha-Agonists↗
PubMed2001

Application of the polysilicone fullerene coating for solid-phase microextraction in the determination of semi-volatile compounds.

Solid-phase microextraction using polysilicone fullerene (PF) coating has been applied for the determination of semi-volatile compounds. Detection limits at the 10 ng l(-1) to approximately microg l(-1) level were achieved using flame ionization detection. A wide linear range was obtained with precision below 7% relative standard deviation. Parameters that affect the extraction process were investigated, which included sampling time, desorption time, sampling temperature, and salting out effect. Compared to the non-polar commercial polydimethylsiloxane (PDMS) coating, the PF coating has higher extraction efficiency, better selectivity and greater sensitivity for aromatic compounds. The experimental results revealed the thermal stability and life span are superior to commercially available PDMS. The PF coating has been demonstrated to possess planarity molecular recognition. The theoretical study confirmed that quantification is feasible under non-equilibrium conditions by use of the PF coating.

Reproducibility of Results↗
PubMed2001

Time-resolved measurement of dissipation-induced decoherence in a Josephson junction.

We determined the dissipation-induced decoherence time (DIDT) of a superconducting Josephson tunnel junction by time-resolved measurements of its escape dynamics. Double-exponential behavior of the time-dependent escape probability was observed, suggesting the occurrence of a two-level decay-tunneling process in which energy relaxation from the excited to the ground level significantly affects the escape dynamics of the system. The observation of temporal double-exponential dependence enables direct measurements of the DIDT, a property critical to the study of quantum dynamics and the realization of macroscopic quantum coherence and quantum computing. We found that the DIDT was tau(d) > 11 micros at T = 0.55 K, demonstrating good prospects for implementing quantum computing with Josephson devices.

Journal Article↗
PubMed2001

Beryllium sensitivity is linked to HLA-DP genotype.

Chronic beryllium disease (CBD) appears to arise from a combination of both exposure and genetic risk factors. A distinguishing feature of CBD is beryllium hypersensitivity, which can be measured in vitro by a lymphocyte proliferation test. The objective of this study was to determine whether certain allelic variations of the HLA-DPB1 gene, which had been observed previously in CBD, could be found in a group of individuals having beryllium hypersensitivity, but no symptoms of CBD. A flow cytometry-based Lymphocyte Proliferation Test combined with immunophenotyping (Immuno-LPT) was used to detect CD4+ and CD8+ T cell proliferation in response to in vitro stimulation with beryllium. The HLA-DPB1 haplotypes of the same individuals were determined by automated DNA sequencing. Twenty-two out of 25 beryllium-sensitive, non-CBD individuals were found to be carriers of the HLA-DPB1 gene having a substitution of a glutamic acid at position 69 in Exon 2 (Glu69), and a significantly high percentage (24%) were Glu69 homozygotes. Most of the CD4+ responders on the Immuno-LPT (10/14) carried rare, non-*0201 Glu69 DPB1 alleles; while most of the non-CD4+ responders (9/11) were common Glu69 carriers (*0201 or *0202) or non-Glu69 individuals (non-Glu69/non-Glu69). This is the first direct evidence that HLA-DP genotype is linked to a phenotypic response that occurs in beryllium sensitization in the absence of clinical CBD.

Berylliosis↗
PubMed2001

Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?

TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription factors (GTFs) needed for expression of genes encoding small cytoplasmic (scRNAs) and small nuclear RNAs (snRNAs). Their activity is stimulated by viral oncogenes, such as SV40 large T antigen and Adenovirus E1A, and is repressed by specific transcription factors (STFs) acting as anti-oncogenes, such as p53 and pRb. GTFs role as final targets of critical signal transduction pathways, that control cell proliferation and differentiation, and their involvement in gene expression regulation suggest that the genes encoding them are potential proto-oncogenes or anti-oncogenes or may be otherwise involved in the pathogenesis of inherited genetic diseases. To test our hypothesis through the positional candidate gene approach, we have determined the physical localization in the human genome of the 11 genes, encoding the subunits of these GTFs, and of three genes for proteins associated with TFIIIB (GTF3BAPs). Our data, obtained by chromosomal in situ hybridization, radiation hybrids and somatic cell hybrids analysis, demonstrate that these genes are present in the human genome as single copy sequences and that some cluster to the same cytogenetic band, alone or in combination with class II GTFs. Intriguingly, some of them are localized within chromosomal regions where recurrent, cytogenetically detectable mutations are seen in specific neoplasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid carcinoma of the salivary glands and hemangiopericytoma, or where mutations causing inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their molecular function and genomic position make these GTF genes interesting candidates for causal involvement in oncogenesis or in the pathogenesis of inherited genetic diseases.

Chromosome Mapping↗
PubMed2001

Differential expression and regulation of AE2 anion exchanger subtypes in rabbit parietal and mucous cells.

1. The anion exchanger isoform 2 (AE2) gene encodes three subtypes (AE2a, b and c), which have different N-termini and tissue distributions. AE2 is expressed at high levels in the stomach, where it is thought to mediate basolateral base exit during acid production. The present study investigated if the three AE2 subtypes are differentially expressed and regulated in different cell types within the gastric mucosa. 2. The cloning strategy to obtain rabbit AE2a, b and c cDNAs combined genomic PCR and RT-PCR based on primers deduced from the rat sequences. Semiquantitative RT-PCR using homologous primers revealed much higher AE2 mRNA expression in rabbit parietal cells (PCs) than in mucous cells (MCs). The subtype expression pattern was AE2b >> AE2c > or = AE2a in PCs and AE2a >AE2b >> AE2c in MCs. Sequence analysis revealed the presence of a highly conserved protein kinase C (PKC) consensus sequence in the AE2a alternative N-terminus. 3. Maximal Cl(-)-HCO(3)(-) exchange rates, measured fluorometrically in BCECF-loaded cultured gastric cells, were much higher in PCs than MCs. PKC activation by phorbol ester stimulated maximal Cl(-)-HCO(3)(-) exchange rates in MCs but not in PCs, whereas forskolin had no effect in each cell type. 4. In summary, rabbit PCs and MCs, which originate from the same gastric stem cell population, display a completely different AE2 subtype expression pattern. Therefore, AE2 subtype expression is not organ specific but cell type specific. The different regulation of anion exchange in parietal and mucous cells suggests that AE2 subtypes may be differentially regulated.

Amino Acid Sequence↗