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Biomedical subjects

N Zhang

Publications and source records attributed to N Zhang.

At least 19 recordsLinked to original sources
PubMed2002

Studies on the epidemiology of bluetongue virus in China.

Sentinel herds of large ruminants were established at five centres in Yunnan Province, Peoples Republic of China, between 1995 and 1997. The application of a sensitive antigen capture ELISA to facilitate virus isolation procedures led to the isolation of 108 strains of bluetongue (BLU) virus. Serotypes isolated included types 1, 2, 3, 4, 9, 11, 12, 15, 16, 21 and 23. Virus transmission occurred over a period of 1-3 months at each of the four positive sites, giving an overall BLU virus transmission period for the province of 5 months, from early June to early November. The greatest level of transmission took place in July and August. The duration of viraemia in individual animals varied from 1 to 7 weeks, with a mean calculated for each serotype between 6 and 20 days. The study represents the first detailed investigation of the epidemiology of BLU in China utilizing sentinel herds.

Animals↗
PubMed2001

Clinical applications of plasma shock wave lithotripsy in treating postoperative remnant stones impacted in the extra- and intrahepatic bile ducts.

BACKGROUND: Choledochofiberscopy with basket extraction has been used widely to treat postoperative remnant stones in the bile duct system. However, it remains difficult to extract stones impacted in the bile duct system or stones too large to pass through the T-tube fistula. This report describes the efficacy and safety of plasma shock wave lithotripsy (PSWL) in fragmenting and eliminating such remnant stones from the bile duct. METHODS: In 52 patients, 117 remnant stones were fragmented with PSWL and subsequently extracted with choledochofiberscopy. The efficacy and safety of PSWL were observed during and after the procedure. RESULTS: After 116 of 117 remnant stones (99.1%) impacted in the extra- and intrahepatic bile ducts were fragmented successfulIy with PSWL, they were extracted with choledochofiberscopy. There were no significant complications during and after the procedure. CONCLUSION: It appears that PSWL is an effective and safe method for fragmenting remnant stones impacted in the bile duct system and stones too large to pass through the T-tube fistula.

Adult↗
PubMed2001

Dimeric DNA quadruplex containing major groove-aligned A-T-A-T and G-C-G-C tetrads stabilized by inter-subunit Watson-Crick A-T and G-C pairs.

We report on an NMR study of unlabeled and uniformly 13C,15N-labeled d(GAGCAGGT) sequence in 1 M NaCl solution, conditions under which it forms a head-to-head dimeric quadruplex containing sequentially stacked G-C-G-C, G-G-G-G and A-T-A-T tetrads. We have identified, for the first time, a slipped A-T-A-T tetrad alignment, involving recognition of Watson-Crick A-T pairs along the major groove edges of opposing adenine residues. Strikingly, both Watson-Crick G-C and A-T pairings within the direct G-C-G-C and slipped A-T-A-T tetrads, respectively, occur between rather than within hairpin subunits of the dimeric d(GAGCAGGT) quadruplex. The hairpin turns in the head-to-head dimeric quadruplex involve single adenine residues and adds to our knowledge of chain reversal involving edgewise loops in DNA quadruplexes. Our structural studies, together with those from other laboratories, definitively establish that DNA quadruplex formation is not restricted to G(n) repeat sequences, with their characteristic stacked uniform G-G-G-G tetrad architectures. Rather, the quadruplex fold is a more versatile and robust architecture, accessible to a range of mixed sequences, with the potential to facilitate G-C-G-C and A-T-A-T tetrad through major and minor groove alignment, in addition to G-G-G-G tetrad formation. The definitive experimental identification of such major groove-aligned mixed A-T-A-T and G-C-G-C tetrads within a quadruplex scaffold, has important implications for the potential alignment of duplex segments during homologous recombination.

Base Pairing↗
PubMed2001

V-shaped scaffold: a new architectural motif identified in an A x (G x G x G x G) pentad-containing dimeric DNA quadruplex involving stacked G(anti) x G(anti) x G(anti) x G(syn) tetrads.

We report the results of an NMR study of unlabeled and uniformly (13)C,(15)N-labeled d(G(3)AG(2)T(3)G(3)AT) in 100 mM NaCl, conditions under which it forms a dimeric quadruplex containing several new topological features. The DNA oligomer chain in each symmetry-related monomer subunit undergoes three sharp turns to form a compact domain, with all the purine bases involved in pairing alignments. The first turn is of the double chain reversal type, the second is of the edgewise type, and the third represents a new alignment, the V-shaped type. Each monomer of the dimeric quadruplex contains two stacked G(anti) x G(anti) x G(anti) x G(syn) tetrads, one of which forms a newly identified A x (G x G x G x G) pentad, through sheared G.A mismatch formation. There is a break in one of the four G-G columns that link adjacent G x G x G x G tetrads within each monomer. This architectural interruption is compensated by a new topological feature of quadruplex architecture, the V-shaped scaffold. The missing G-G column results in an opening that could facilitate insertion of planar ligands into the quadruplex. The dimeric interface contains stacked A.(G.G.G.G) pentads, with each pentad containing four bases from one monomer and a syn G1 from the partner monomer. Several potential ligand-binding pockets, positioned towards either end of the folded architecture, were identifiable in a surface view of the solution structure of the dimeric d(G(3)AG(2)T(3)G(3)AT) quadruplex.

Base Sequence↗
PubMed2001

A DNA polymorphism specific to Candida albicans strains exceptionally successful as human pathogens.

A large proportion of infection-causing isolates of the yeast Candida albicans belong to a general-purpose genotype, identifiable by fingerprinting with the moderately repetitive sequence Ca3. The high prevalence of this group -- up to 70% in some patient categories -- suggests that its members possess genetic determinants, which enhance their success as pathogens compared to other strains. To find such determinants we are comparing the genomes of representatives of the general-purpose genotype cluster with the genomes of other strains. In this paper we describe the identification of a 985 bp HpaII fragment (MU13-4) specific to general-purpose genotype strains. The fragment was present in 90% of these strains, but only in 10% of other strains. The fragment did not hybridize with probe Ca3, used to define the general-purpose cluster. It contains elevated levels of repetitive DNA. Sequences homologous to MU13-4 are dispersed throughout the chromosomes of general-purpose strains but are rarer or absent in other strains, as judged by Southern hybridization. Using the Stanford C. albicans genome database, we have placed the MU13-4 fragment next to a CARE-1 element. We also found 79 significant homologies between parts of MU13-4 and 19 other contigs. Attempts to amplify the region surrounding the polymorphic fragment in non-general-purpose genotype strains suggest, as do the hybridization data, that the polymorphism is created by a deletion in non-cluster strains. These results show that it is possible to identify polymorphisms specific to general-purpose genotype strains. Primers against the fragment will allow PCR-based discrimination between general-purpose genotype strains and other strains, facilitating investigations aimed at determining morbidity and mortality caused by general-purpose genotype strains compared to other strains.

Base Sequence↗
PubMed2001

Two-layer sample preparation method for MALDI mass spectrometric analysis of protein and peptide samples containing sodium dodecyl sulfate.

Sodium dodecyl sulfate (SDS) is widely used in protein sample workup. However, many mass spectrometric methods cannot tolerate the presence of this strong surfactant in a protein sample. We present a practical and robust technique based on a two-layer matrix/sample deposition method for the analysis of protein and peptide samples containing SDS by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The two-layer method involves the deposition of a mixture of sample and matrix on top of a thin layer of matrix crystals. It was found that for SDS-containing samples, the intensity of the MALDI signals can be affected by the conditions of sample preparation: on-probe washing, choice of matrix, deposition method, solvent system, and protein-to-SDS ratio. However, we found that, under appropriate conditions, the two-layer method gave reliable MALDI signals for samples with levels of SDS up to approximately 1%. The applications of this method are demonstrated for MALDI analysis of hydrophobic membrane proteins as well as bacterial extracts. We envision that this two-layer method capable of handling impure samples including those containing SDS will play an important role in protein molecular weight analysis as well as in proteome identification by MALDI-MS and MS/MS.

Bacterial Proteins↗
PubMed2001

[Effect of aldose reductase expression by transforming growth factor-beta1 on rat mesangial cell].

OBJECTIVE: To screen the responsive genes related to transforming growth factor-beta1 (TGF-beta1) in rat mesangial cell (MsC) transfected by human TGF-beta1 gene, using suppression subtractive hybridization PCR (SSH-PCR); then to detect the expression of aldose reductase gene on cultured rat MsC and renal cortex of rats with anti-Thy1 glomerulonephritis. METHODS: SSH-PCR technique and differential screening for detecting the responsive genes related to TGF-beta1; Semi-quantification RT-PCR and Western blot analysis for identifying the expression of aldose reductase on MsC in vitro and in vivo. RESULTS: Compared with normal MsC, it was proved that 28 responsive genes related to TGF-beta1 in MTG1. There was an expression sequence tag (EST), approximate 337 bp segment, completely identical to the data of aldose reductase gene from GenBank. Elevated levels of aldose reductase mRNA and protein were found on cultured rat MsC treated with TGF-beta1 and renal cortex of rat with anti-Thy1 glomerulonephritis. CONCLUSION: Aldose reductase, rate-limiting enzyme in the polyol pathway, was closely related to TGF-beta1 expression. It is possible that upregulation of aldose reductase expression may be involved in the development of glomerulosclerosis mediated by TGF-beta1.

Aldehyde Reductase↗
PubMed2001

MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines.

A series of 4-anilino-3-cyano-6,7-dialkoxyquinolines with different substituents attached to the 4-anilino group has been prepared that are potent MEK (MAP kinase kinase) inhibitors. The best activity is obtained when a phenyl or a thienyl group is attached to the para-position of the aniline through a hydrophobic linker, such as an oxygen, a sulfur, or a methylene group. The most active compounds show low nanomolar IC(50)'s against MEK (MAP kinase kinase), and have potent growth inhibitory activity in LoVo cells (human colon tumor line).

Aniline Compounds↗
PubMed2001

Functional Analysis of six novel ORFs on the left arm of Chromosome XII of Saccharomyces cerevisiae reveals three of them responding to S-starvation.

Six novel Open Reading Frames (ORFs) located on the left arm of the chromosome XII (YLL061w, YLL060c, YLL059c, YLL058w, YLL057c and YLL056c) have been analysed using either short-flanking homology (SFH) or long-flanking homology (LFH) gene replacement. Sporulation and tetrad analysis showed none of these ORFs to be essential for vegetative growth. The standard EUROFAN growth tests failed to reveal any obvious phenotypes resulting from deletion of each of the ORFs. Bioinformatic analysis revealed that YLL061w is probably an amino acid permease for S-methylmethionine and that YLL060c encodes a glutathione transferase which is involved in cellular detoxification, while YLL058w may play a role in sulphur-containing amino-acid metabolism, YLL057c in sulphonate catabolism and YLL056c in stress response. The transcription of three ORFs (YLL061w, YLL057c and YLL056c) has been shown to increase more than 10-fold under sulphate starvation. Replacement cassettes, comprising the kanMX marker flanked by each ORF's promoter and terminator regions, were cloned into pUG7. All the cognate clones, were generated using direct PCR products amplified from genomic DNA or using gap-repair. All clones and strains produced have been deposited in the EUROFAN genetic stock centre (EUROSCARF, Frankfurt).

Amino Acid Transport Systems↗
PubMed2001

Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles.

Screening of a directed compound library in a yeast-based assay identified 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (2a) as a Src inhibitor. An enzymatic assay established that 2a was an ATP-competitive inhibitor of the kinase activity of Src. We present here SAR data for 2a which shows that the aniline group at C-4, the carbonitrile group at C-3, and the alkoxy groups at C-6 and C-7 of the quinoline are crucial for optimal activity. Increasing the size of the C-2 substituent of the aniline at C-4 of 2a from chloro to bromo to iodo resulted in a corresponding increase in Src inhibition. Furthermore, replacement of the 7-methoxy group of 2a with various 3-heteroalkylaminopropoxy groups provided increased inhibition of both Src enzymatic and cellular activity. Compound 25, which contains a 3-morpholinopropoxy group, had an IC(50) of 3.8 nM in the Src enzymatic assay and an IC(50) of 940 nM for the inhibition of Src-dependent cell proliferation.

Aniline Compounds↗
PubMed2001

Relationships involving metastable equilibrium solubility, surface complexes, and crystallite disorder with carbonated apatites.

Previous studies have shown that the metastable equilibrium solubility (MES) behavior of carbonated apatites (CAPs) may be described by a surface complex with the hydroxyapatite (HAP) stoichiometry in the absence of solution fluoride and by that with the fluorapatite (FAP) stoichiometry when appreciable solution fluoride is present. Studies have also shown that the magnitude of the MES is directly related to the crystallinity of the CAP. The aim of the present investigation was to examine the relationship between the CAP MES determined in the presence of solution fluoride and CAP crystallinity and to examine the effect of the change in the stoichiometry of the surface complex (from that of HAP to that of FAP) upon the relationship of the CAP MES to crystallinity. CAP samples were prepared by methods based on the precipitation of CAP from calcium phosphate solutions and the hydrolysis of dicalcium phosphate dihydrate in bicarbonate solutions. From X-ray diffraction experiments, the crystallite microstrain, and the full width at half maximum (FWHM) of the 002 reflection were determined for the CAPs. From CAP MES experiments conducted in the presence of solu tion fluoride, linear plots of the mean MES (i.e., mean pK(FAP)) values vs the crystallinity parameter (i.e., microstrain and FWHM) were obtained that yielded slopes that were essentially the same as those obtained in the absence of solution fluoride (i.e., mean pK(HAP) values vs crystallinity). This parallel finding suggests that the CAP crystallite disorder affects the energetics of the two surface complexes essentially to the same extent and provides new insight into the nature of CAP surface complexes.

Apatites↗
PubMed2001

Involvement of apoptosis in neurological injury after hypothermic circulatory arrest: a new target for therapeutic intervention?

BACKGROUND: This study was undertaken to evaluate the role of apoptosis in neurological injury after hypothermic circulatory arrest (HCA). METHODS: Twenty-one pigs (27 to 31 kg) underwent 90 minutes of HCA at 20 degrees C and were electively sacrificed at 6, 24, 48, and 72 hours, and at 7, 10, and 12 days after HCA, and compared with unoperated controls. In addition, 3 animals that had HCA at 10 degrees C, and 3 treated with cyclosporine A (CsA) in conjunction with HCA at 20 degrees C, were examined 72 hours after HCA. After selective perfusion and cryopreservation, all brains were examined to visualize apoptotic DNA fragmentation and chromatin condensation on the same cryosection of the hippocampus: fluorescent in situ end labeling (ISEL) was combined with staining with a nucleic acid-binding cyanine dye (YOYO). RESULTS: In addition to apoptosis, which was seen at a significantly higher level (p = 0.05) after HCA than in controls, two other characteristic degenerative morphological cell types (not seen in controls) were characterized after HCA. Cell death began 6 hours after HCA and reached its peak at 72 hours, but continued for at least 7 days. Compared with the standard protocol at 20 degrees C, HCA at 10 degrees C and CsA treatment both significantly reduced overall cell death after HCA, but not apoptosis. CONCLUSIONS: The data establish that significant neuronal apoptosis occurs as a consequence of HCA, but at 20 degrees C, other pathways of cell death, probably including necrosis, predominate. Although preliminary results suggest that the neuroprotective effects of lower temperature and of CsA are not a consequence of blockade of apoptotic pathways, inhibition of apoptosis nevertheless seems promising as a strategy to protect the brain from the subtle neurological injury that is associated with prolonged HCA at clinically relevant temperatures.

Animals↗
PubMed2001

Expression of Deltex1 during mouse embryogenesis: comparison with Notch1, 2 and 3 expression.

The Notch signalling pathway defines a phylogenetically conserved cell-cell communication process that enables cell-fate specification in multicellular organisms. Deltex is a component of the Notch signalling network that physically interacts with the ankyrin repeats of Notch. Here, we report on the expression pattern of the Deltex1 gene during mouse embryonic development and, furthermore, we compare its expression with that of the Notch1, 2 and 3 genes. Complementary and combinatorial expression patterns between Deltex1 and the three Notch genes were observed throughout embryogenesis since Deltex1 expression was related either to cytodifferentiation (i.e. neuronal tissues) or to cell proliferation events (i.e. eye, vascular structures, hematopoiesis).

Animals↗
PubMed2001

Cyclosporine A as a potential neuroprotective agent: a study of prolonged hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: To assess whether Cyclosporine A (CsA) or cycloheximide (CHX) can reduce ischemia-induced neurological damage by blocking apoptotic pathways, we assessed their effects on cerebral recovery in a chronic animal model of hypothermic circulatory arrest (HCA). METHODS: Twenty-eight pigs (28-33 kg) underwent 90 min of HCA at 20 degrees C. In this blinded study, animals were randomized to placebo (n=12), 5 mg/kg CsA (n=8), given intravenously before and subcutaneously for 7 days after HCA, or a single dose of 1 mg/kg CHX (n=8), given after weaning from cardiopulmonary bypass. Hemodynamics, intracranial pressure (ICP) and neurophysiological data (EEG, SSEP) were assessed for 3 h after HCA; early behavioral recovery was scored, and neurological/behavioral evaluation (9=normal) was carried out daily until elective sacrifice on postoperative day (POD) 7. Brains were selectively perfused and evaluated histopathologically for apoptosis. RESULTS: Basic hemodynamic data revealed no differences between CsA or CHX and control groups. ICP was significantly lower throughout rewarming (P=0.009) and reperfusion (P=0.05) in the CsA group. EEG recovery 3 h after HCA was observed in four of eight CsA animals but in only 1 of 12 controls (P=0.11) and one of eight CHX animals; cortical SSEP recovery also seemed faster in CsA animals, but failed to reach significance. Some early recovery scores were significantly better in the CsA group, and daily behavioral scores were consistently and significantly higher in the CsA-treated animals from POD1 through POD4. CONCLUSIONS: The data indicate that treatment with Cyclosporine A but not cycloheximide has a positive effect on cerebral recovery following HCA. Whether CsA results in inhibition of neuronal apoptosis, and/or inhibits release of cytokines and thereby reduces postischemic cerebral edema remains to be elucidated. The neuroprotective effect of CsA, if confirmed in further studies, would make its clinical application conceivable.

Animals↗
PubMed2001

The ties that bind what is known to the recognition of what is new.

Recognition success varies with how information is encoded (e.g., level of processing) and with what is already known as a result of past learning (e.g., word frequency). This article presents the results of experiments showing that preexisting connections involving the associates of studied words facilitate their recognition regardless of whether the words are intentionally encoded or are incidentally encoded under semantic or nonsemantic conditions. Words are more likely to be recognized when they have either more resonant connections coming back to them from their associates or more connections among their associates. Such results occur even though attention is never drawn to these associates. Regression analyses showed that these connections affect recognition independently of frequency, so the present results add to the literature showing that prior lexical knowledge contributes to episodic recognition. In addition, equations that use free-association data to derive composite strength indices of resonance and connectivity were evaluated. Implications for theories of recognition are discussed.

Adult↗
PubMed2001

A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations.

A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent, " that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY-an abbreviation for functional analysis by co-responses in yeast.

Adenine Nucleotides↗