Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 199 records · Page 11Linked to original sources

PubMed2001

Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation.

BACKGROUND: The purpose of this study was to determine how often accessory atrioventricular (AV) pathways (AP) cross the AV groove obliquely. With an oblique course, the local ventriculoatrial (VA) interval at the site of earliest atrial activation (local-VA) and the local-AV interval at the site of earliest ventricular activation (local-AV) should vary by reversing the direction of the paced ventricular and atrial wavefronts, respectively. METHODS AND RESULTS: One hundred fourteen patients with a single AP were studied. Two ventricular and two atrial pacing sites on opposite sides of the AP were selected to reverse the direction of the ventricular and atrial wavefronts along the annulus. Reversing the ventricular wavefront increased local-VA by >/=15 ms in 91 of 106 (91%) patients. With the shorter local-VA, the ventricular potential overlapped the atrial potential along a 17.2+/-8.5-mm length of the annulus. No overlap occurred with the opposite wavefront. Reversing the atrial wavefront increased local-AV by >/=15 ms in 32 of 44 (73%) patients. With the shorter local-AV, the atrial potential overlapped the ventricular potential along an 11.9+/-8.9-mm length of the annulus. No overlap occurred with the opposite wavefront. Mapping during longer local-VA or local-AV identified an AP potential in 102 of 114 (89%) patients. Catheter ablation eliminated AP conduction in all 111 patients attempted (median, 1 radiofrequency application in 99 patients with an AP potential versus 4.5 applications without an AP potential). CONCLUSIONS: Reversing the direction of the paced ventricular or atrial wavefront reveals an oblique course in most APs and facilitates localization of the AP potential for catheter ablation.

Adolescent↗

PubMed2001

Reactive oxygen and NF-kappaB in VEGF-induced migration of human vascular smooth muscle cells.

Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human coronary arteries, we determined if VEGF could stimulate VSMC migration and the intracellular signals involved. VEGF induced VSMC migration but had no significant activity on proliferation. VEGF increased intracellular reactive oxygen species (ROS), NF-kappaB activation and IL-6 expression. Blockade of the generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-kappaB activation, IL-6 expression, and cell migration indicating that generation of ROS was required for NF-kappaB activation and the chemotactic activity of VEGF. Expression of a mutated, nondegradable form of inhibitor of NF-kappaB (IkappaB-alphaM) suppressed VEGF-triggered activation of NF-kappaB and upregulation of IL-6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly attenuated the migration stimulated by VEGF. Collectively, our data provide the first evidence that intracellular ROS and NF-kappaB are required for VEGF-mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved in the ability of the growth factor to stimulate migration.

Antioxidants↗

PubMed2001

Telomerase activation by histone deacetylase inhibitor in normal cells.

Although telomerase activity is known to be regulated mainly at the level of transcription of the human telomerase catalytic subunit (hTERT) gene, the molecular mechanism underlying tumor-specific expression of telomerase remains unclear. Emerging evidence suggests that reversible acetylation of nucleosomal histones and the resultant changes in the chromatin structure are important processes in gene transcription. In particular, histone deacetylase (HDAC) inhibitors activate the transcription of certain genes by altering the acetylation status of nucleosomal histones. The present study examines the effects of HDAC inhibitor on hTERT gene transcription. Treatment with tricostatin A (TSA) induced significant activation of hTERT mRNA expression and telomerase activity in normal cells, but not in cancer cells. Transient expression assays revealed that TSA activates the hTERT promoter. Furthermore, the proximal 181 bp core promoter of hTERT, which contains two c-Myc and five Sp1 sites, was determined to be the responsible element. Overexpression of Sp1 enhanced responsiveness to TSA, and mutation of Sp1 sites, but not c-Myc sites, of the core promoter of hTERT abrogated this activation. Introduction of the dominant-negative form of the Sp family inhibited TSA activation. These results indicate that HDAC inhibitor activates the hTERT promoter in normal cells, in which Sp1 plays a key role. This finding suggests one way whereby histone deacetylation may be involved in silencing the hTERT gene in normal cells.

Acetyltransferases↗

PubMed2001

Accessibility of DNA polymerases to repair synthesis during nucleotide excision repair in yeast cell-free extracts.

Nucleotide excision repair (NER) removes a variety of DNA lesions. Using a yeast cell-free repair system, we have analyzed the repair synthesis step of NER. NER was proficient in yeast mutant cell-free extracts lacking DNA polymerases (Pol) beta, zeta or eta. Base excision repair was also proficient without Polbeta. Repair synthesis of NER was not affected by thermal inactivation of the temperature-sensitive mutant Polalpha (pol1-17), but was reduced after thermal inactivation of the temperature-sensitive mutant Poldelta (pol3-1) or Polvarepsilon (pol2-18). Residual repair synthesis was observed in pol3-1 and pol2-18 mutant extracts, suggesting a repair deficiency rather than a complete repair defect. Deficient NER in pol3-1 and pol2-18 mutant extracts was specifically complemented by purified yeast Poldelta and Polvarepsilon, respectively. Deleting the polymerase catalytic domain of Polvarepsilon (pol2-16) also led to a deficient repair synthesis during NER, which was complemented by purified yeast Polvarepsilon, but not by purified yeast Poleta. These results suggest that efficient repair synthesis of yeast NER requires both Poldelta and Polvarepsilon in vitro, and that the low fidelity Poleta is not accessible to repair synthesis during NER.

Catalytic Domain↗

PubMed2001

Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3.

Transgenic expression in the hypothalamus of syndecan-1, a cell surface heparan sulfate proteoglycan (HSPG) and modulator of ligand-receptor encounters, produces mice with hyperphagia and maturity-onset obesity resembling mice with reduced action of alpha melanocyte stimulating hormone (alphaMSH). Via their HS chains, syndecans potentiate the action of agouti-related protein and agouti signaling protein, endogenous inhibitors of alphaMSH. In wild-type mice, syndecan-3, the predominantly neural syndecan, is expressed in hypothalamic regions that control energy balance. Food deprivation increases hypothalamic syndecan-3 levels several-fold. Syndecan-3 null mice, otherwise apparently normal, respond to food deprivation with markedly reduced reflex hyperphagia. We propose that oscillation of hypothalamic syndecan-3 levels physiologically modulates feeding behavior.

Aging↗

PubMed2001

Translesion synthesis by the UmuC family of DNA polymerases.

Translesion synthesis is an important cellular mechanism to overcome replication blockage by DNA damage. To copy damaged DNA templates during replication, specialized DNA polymerases are required. Translesion synthesis can be error-free or error-prone. From E. coli to humans, error-prone translesion synthesis constitutes a major mechanism of DNA damage-induced mutagenesis. As a response to DNA damage during replication, translesion synthesis contributes to cell survival and induced mutagenesis. During 1999-2000, the UmuC superfamily had emerged, which consists of the following prototypic members: the E. coli UmuC, the E. coli DinB, the yeast Rad30, the human RAD30B, and the yeast Rev1. The corresponding biochemical activities are DNA polymerases V, IV, eta, iota, and dCMP transferase, respectively. Recent studies of the UmuC superfamily are summarized and evidence is presented suggesting that this family of DNA polymerases is involved in translesion DNA synthesis.

Bacterial Proteins↗

PubMed2001

[Microanatomical study of transcerebellomedullary fissure approach].

OBJECTIVE: To study the anatomy of structures on the way to the fourth ventricle of cerebrum via transcerebellomedullary fissure approach. METHODS: Ten cadaveric heads fixed with formalin and with their arteries and veins perfused with color latex were dissected with nicrosurgical anatomical skills to observe the structure of tela choroida, fourth ventricle roof, rhomboid fossa, and posterior inferior cerebellar artery (PICA) and its branches. RESULTS: Via the transcerebellomedullary fissure approach, any part of the rhomboid fossa can be reached by exposing and separating the tela choroida, inferior medullary velum, and nodule of vermis, and the dorsolateral part of pons and of medulla obligata can be reached by lateral recess. CONCLUSION: The fourth ventricle of cerebrum and the lateral parts of brainstem can be reached via transcerebellomedullary fissure approach through normal anatomical spaces. The tonsilomedullary and telovelotonsillar segments of PICA are the most important vessels in the transcerebellomedullary fissure approach.

Brain Stem↗

PubMed2001

[Treatment of dyskinetic disorders with tremor by lesioning and DBS of Vim].

OBJECTIVE: To explore the effect of stereotactic operation in treatment of dyskinetic disorders with tremor as the main symptom and to study the value of anatomic location and microelectrode functional location. METHODS: Surgiplan system and microelectrode direction technique were used to locate the Vim, and then target lesioning and deep brain simulation (DBS) were performed in 22 patients with dyskinetic disorders with tremor. After the operation, a follow-up was conducted for 6 approximately 12 months. RESULTS: After the operation, tremor disappeared in 21 patients and hypermyotonia was improved in 13 cases. During the follow-up tremor completely disappeared in 18 patients, including 3 cases treated with DBS, was markedly alleviated in 3 cases and was slightly improved in one case. Typical cell firing at tremor was recorded in 17 cases during the operation. CONCLUSION: The surgiplan system and microelectrode recording technique play an important role in location of Vim. Accurate location is crucial for success of operation. The curative effect of DBS is similar as lesioning operation.

Adult↗

PubMed2001

Regional variation in the incidence of end-stage renal disease in Indigenous Australians.

OBJECTIVE: To evaluate regional variation in the incidence of end-stage renal disease (ESRD) in Indigenous Australians, and to examine the proximity to ESRD treatment facilities of Indigenous patients. DESIGN: Secondary data review, with collection of primary data regarding patients' place of residence before beginning ESRD treatment. PARTICIPANTS: Indigenous ESRD patients who commenced treatment in Australia during 1993-1998. METHODS: We obtained data from the Australian and New Zealand Dialysis and Transplant Registry regarding 719 Indigenous patients who started ESRD treatment between 1 January 1993 and 31 December 1998. We obtained primary data from the treating renal units to determine the place of residence before beginning renal replacement therapy. We calculated the average annual incidence of ESRD for each of the 36 Aboriginal and Torres Strait Islander Commission regions using population estimates based on the 1996 Census, and calculated standardised incidence ratios with 95% confidence intervals for each region. We compared the number of cases with the treatment facilities available in each region. MAIN OUTCOME MEASURE: Regional standardised ESRD incidence for Indigenous Australians referenced to the total resident population of Australia. RESULTS: Standardised ESRD incidence among Indigenous Australians is highest in remote regions, where it is up to 30 times the national incidence for all Australians. In urban regions the standardised incidence is much lower, but remains significantly higher than the national incidence. Forty-eight per cent of Indigenous ESRD patients come from regions without dialysis or transplant facilities and 16.3% from regions with only satellite dialysis facilities. CONCLUSIONS: There is marked regional variation in the incidence of ESRD among Indigenous Australians. Because of the location of treatment centres, there is inequitable access to ESRD treatment services for a significant proportion of Indigenous patients.

Australia↗

PubMed2001

A fluorescence spectroscopic study of phenanthrene sorption on porous silica.

Fluorescence spectroscopic characteristics of sorbed phenanthrene in porous silica provide information about its chemical state such as monomer vs dimer or higher aggregates, as well as a basis for high sensitivity detection. In this study, the chemical state and distribution of phenanthrene sorbed in two types of porous silica particles, mesoporous silica (365 microns particle diameter, 150 A average pore diameter) and microporous silica (custom synthethized, 1 micron particle diameter, 20 A pore diameter), is determined by fluorescence spectroscopy, fluorescence lifetime measurements, and scanning two-photon excitation fluorescence profiling. From the characteristic fluorescence emission spectra, it is found that at loading levels of < or = 4.7 mg/g (phenanthrene/silica) phenanthrene exists as monomers in both meso- and microporous silica particles for phenanthrene loaded from super critical CO2 (SCF). Two-photon excitation fluorescence intensity distribution profiles indicate that for the mesoporous silica particles phenanthrene is adsorbed throughout the entire silica particle. Introduction of water into phenanthrene-loaded mesoporous silica particles causes instantaneous conversion of phenanthrene from monomer to crystalline form at phenantherene loading levels > or = 4.7 micrograms/g due to hydration of the silica surface. In this process, sorption of water molecules expels phenanthrene from the surface sorption sites and causes localized phenanthrene concentration beyond its solubility limit, resulting in crystallization. In comparison this fast conversion is not observed for phenanthrene-loaded microporous silica particles that show extremely slow conversion even for phenanthrene loading levels as high as 4.7 mg/g. This difference is interpreted as reflecting hindered diffusion of phenanthrene in the nearly monodispersed micropores with pore sizes close to the molecular diameter of phenanthrene.

Absorption↗

PubMed2001

Translesion synthesis by yeast DNA polymerase zeta from templates containing lesions of ultraviolet radiation and acetylaminofluorene.

In the yeast Saccharomyces cerevisiae, DNA polymerase zeta (Polzeta) is required in a major lesion bypass pathway. To help understand the role of Polzeta in lesion bypass, we have performed in vitro biochemical analyses of this polymerase in response to several DNA lesions. Purified yeast Polzeta performed limited translesion synthesis opposite a template TT (6-4) photoproduct, incorporating A or T with similar efficiencies (and less frequently G) opposite the 3' T, and predominantly A opposite the 5' T. Purified yeast Polzeta predominantly incorporated a G opposite an acetylaminofluorene (AAF)-adducted guanine. The lesion, however, significantly inhibited subsequent extension. Furthermore, yeast Polzeta catalyzed extension DNA synthesis from primers annealed opposite the AAF-guanine and the 3' T of the TT (6-4) photoproduct with varying efficiencies. Extension synthesis was more efficient when A or C was opposite the AAF-guanine, and when G was opposite the 3' T of the TT (6-4) photoproduct. In contrast, the 3' T of a cis-syn TT dimer completely blocked purified yeast Polzeta, whereas the 5' T was readily bypassed. These results support the following dual-function model of Polzeta. First, Polzeta catalyzes nucleotide incorporation opposite AAF-guanine and TT (6-4) photoproduct with a limited efficiency. Secondly, more efficient bypass of these lesions may require nucleotide incorporation by other DNA polymerases followed by extension DNA synthesis by Polzeta.

2-Acetylaminofluorene↗

PubMed2001

Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells.

Interactions between the checkpoint abrogator UCN-01 and several pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway have been examined in a variety of human leukemia cell lines. Exposure of U937 monocytic leukemia cells to a marginally toxic concentration of UCN-01 (e.g., 150 nM) for 18 h resulted in phosphorylation/activation of p42/44 MAPK. Coadministration of the MEK inhibitor PD184352 (10 microM) blocked UCN-01-induced MAPK activation and was accompanied by marked mitochondrial damage (e.g., cytochrome c release and loss of DeltaPsi(m)), caspase activation, DNA fragmentation, and apoptosis. Similar interactions were noted in the case of other MEK inhibitors (e.g., PD98059; U0126) as well as in multiple other leukemia cell types (e.g., HL-60, Jurkat, CCRF-CEM, and Raji). Coadministration of PD184352 and UCN-01 resulted in reduced binding of the cdc25C phosphatase to 14-3-3 proteins, enhanced dephosphorylation/activation of p34(cdc2), and diminished phosphorylation of cyclic AMP-responsive element binding protein. The ability of UCN-01, when combined with PD184352, to antagonize cdc25C/14-3-3 protein binding, promote dephosphorylation of p34(cdc2), and potentiate apoptosis was mimicked by the ataxia telangectasia mutation inhibitor caffeine. In contrast, cotreatment of cells with UCN-01 and PD184352 did not substantially increase c-Jun-NH(2)-terminal kinase activation nor did it alter expression of Bcl-2, Bcl-x(L), Bax, or X-inhibitor of apoptosis. However, coexposure of U937 cells to UCN-01 and PD184352 induced a marked increase in p38 MAPK activation. Moreover, SB203580, which inhibits multiple kinases including p38 MAPK, partially antagonized cell death. Lastly, although UCN-01 +/- PD184352 did not induce p21(CIP1), stable expression of a p21(CIP1) antisense construct significantly increased susceptibility to this drug combination. Together, these findings indicate that exposure of leukemic cells to UCN-01 leads to activation of the MAPK cascade and that interruption of this process by MEK inhibition triggers perturbations in several signaling and cell cycle regulatory pathways that culminate in mitochondrial injury, caspase activation, and apoptosis. They also raise the possibility that disrupting multiple signaling pathways, e.g., by combining UCN-01 with MEK inhibitors, may represent a novel antileukemic strategy.

Alkaloids↗

PubMed2001

Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.

Serum response factor (SRF) regulates transcription of numerous muscle and growth factor-inducible genes. Because SRF is not muscle specific, it has been postulated to activate muscle genes by recruiting myogenic accessory factors. Using a bioinformatics-based screen for unknown cardiac-specific genes, we identified a novel and highly potent transcription factor, named myocardin, that is expressed in cardiac and smooth muscle cells. Myocardin belongs to the SAP domain family of nuclear proteins and activates cardiac muscle promoters by associating with SRF. Expression of a dominant negative mutant of myocardin in Xenopus embryos interferes with myocardial cell differentiation. Myocardin is the founding member of a class of muscle transcription factors and provides a mechanism whereby SRF can convey myogenic activity to cardiac muscle genes.

Amino Acid Sequence↗

PubMed2001

Synthesis of novel acetal thia-cage compounds.

The synthesis of novel acetal thia-cage compounds has been accomplished by the direct substitution for the oxygen atom by the sulfur atom in the reaction of the acetal groups of oxa-cages with Lawesson reagent (LR). Reaction of the tetraoxa-cage compound 2 with LR in dichloromethane at 25 degrees C sequentially gave the monothia-, dithia-, trithia-, and tetrathia-cage compounds 3, 6, 7, and 9. The reaction mechanism for the conversion from oxa-cages into thia-cages was proposed. The diacetal trioxa-cages 18-20 and 24-26 were also transformed into the thia-cages 21-23 and 27-29, respectively. Reaction of the trioxa-cages 34 and 35 with LR under the same reaction conditions gave the thia-cages 36 and 37 with the carbonyl group intact. Treatment of the pentaoxa[5]peristylane 40 with LR in chloroform under supersonic shaking at refluxing temperature gave the monothia[5]peristylane 41 and the dithia[5]peristylane 42. Attempts to synthesize the thia[5]peristylanes from the tetraoxa-cage 51 and the transformation from the parent (unsubstituted) pentaoxa[5]peristylane 46 to the thia-cages have been made. Reaction of the pentaoxa[5]-peristylane 40 with P(2)S(5) in refluxing toluene gave 41, 42, and a rearrangement product 47. The synthesis of new heterocyclic cage compounds 59 and 60, which contain oxygen, nitrogen, and sulfur atoms in the same molecule, was also accomplished.

Journal Article↗

PubMed2001

Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2.

Plakophilin 2, a member of the arm-repeat protein family, is a dual location protein that occurs both in the cytoplasmic plaques of desmosomes as an architectural component and in an extractable form in the nucleoplasm. Here we report the existence of two nuclear particles containing plakophilin 2 and the largest subunit of RNA polymerase (pol) III (RPC155), both of which colocalize and are coimmunoselected with other pol III subunits and with the transcription factor TFIIIB. We also show that plakophilin 2 is present in the pol III holoenzyme, but not the core complex, and that it binds specifically to RPC155 in vitro. We propose the existence of diverse nuclear particles in which proteins known as plaque proteins of intercellular junctions are complexed with specific nuclear proteins.

Animals↗

PubMed2001

Effects of low intensity radiofrequency electromagnetic fields on electrical activity in rat hippocampal slices.

Slices of rat hippocampus were exposed to 700 MHz continuous wave radiofrequency (RF) fields (25.2-71.0 V m(-1), 5-15 min exposure) in a stripline waveguide. At low field intensities, the predominant effect on the electrically evoked field potential in CA1 was a potentiation of the amplitude of the population spike by up to 20%, but higher intensity fields could produce either increases or decreases of up to 120 and 80%, respectively, in the amplitude of the population spike. To eliminate the possibility of RF-induced artefacts due to the metal stimulating electrode, the effect of RF exposure on spontaneous epileptiform activity induced in CA3 by 4-aminopyridine (50-100 microM) was investigated. Exposure to RF fields (50.0 V m(-1)) reduced or abolished epileptiform bursting in 36% of slices tested. The maximum field intensity used in these experiments, 71.0 V m(-1), was calculated to produce a specific absorption rate (SAR) of between 0.0016 and 0.0044 W kg(-1) in the slices. Measurements with a Luxtron fibreoptic probe confirmed that there was no detectable temperature change (+/- 0.1 degrees C) during a 15 min exposure to this field intensity. Furthermore, imposed temperature changes of up to 1 degrees C failed to mimic the effects of RF exposure. These results suggest that low-intensity RF fields can modulate the excitability of hippocampal tissue in vitro in the absence of gross thermal effects. The changes in excitability may be consistent with reported behavioural effects of RF fields.

Action Potentials↗

PubMed2001

[Resection of neoplasm in fourth ventricle and at the back of pons through cerebellomedullary fissure approach].

OBJECTIVE: To investigate the advantage of cerebellomedullary fissure approach to resect the space occupying lesion in the fourth ventricle region and at the back of pons and to discuss the microsurgical skills. METHODS: The craniotomy is through the posterior fossa. To maximize the width of exposure, a long skin incision is made from the occipital protuberance down to the C4-5 level, and a free occipital bone flap is turned. The tonsils of cerebellum are reached by opening the tonsillovermian fissure and then moved upward so as to expose the operating field. Neoplasm in the fourth ventricle and at the back of pons was resected. RESULTS: Among the 23 cases, total resection was achieved in 20, and subtotal resection in 3. CONCLUSION: The cerebellomedullary fissure approach can provide a panoramic view between the two lateral recesses and from the obex to the aqueduct without excision of neural tissue. During the operation, the inferior vermis is not incised. The vessels and nervous tissue are extracted at a minimum extent. Such a procedure is much safer.

Adolescent↗

PubMed2001

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo.

We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was confirmed by RT--PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated filters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.

Alternative Splicing↗