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Biomedical subjects

W Zhu

Publications and source records attributed to W Zhu.

At least 127 records · Page 7Linked to original sources
PubMed2000

Direct observation of trapping and release of nitric oxide by glutathione and cysteine with electron paramagnetic resonance spectroscopy.

While the biosynthesis of nitric oxide (NO) is well established, one of the key issues that remains to be solved is whether NO participates in the biological responses right after generation through biosynthesis or there is a "secret passage" via which NO itself is trapped, transported, and released to exert its functions. It has been shown that NO reacts with thiol-containing biomolecules (RSH), like cysteine (Cys), glutathione (GSH), etc., to form S-nitrosothiols (RSNOs), which then release nitrogen compounds, including NO. The direct observation of trapping of NO and its release by RSNO has not been well documented, as most of the detection techniques measure the content of NO as well as nitrite and nitrate. Here we use spin-trapping electron paramagnetic resonance (EPR) technique to measure NO content directly in the reaction time course of samples of GSH and Cys ( approximately mM) mixed with NO ( approximately microM) in the presence of metal ion chelator, which pertains to physiological conditions. We demonstrate that NO is readily trapped by these thiols in less than 10 min and approximately 70-90% is released afterward. These data imply that approximately 10-30% of the reaction product of NO does not exist in the free radical form. The NO release versus time curves are slightly pH dependent in the presence of metal ion chelator. Because GSH and Cys exist in high molar concentrations in blood and in mammalian cells, the trapping and release passage of NO by these thiols may provide a mechanism for temporal and spatial sequestration of NO to overcome its concentration gradient-dependent diffusion, so as to exert its multiple biological effects by reacting with various targets through regeneration.

Copper↗
PubMed2000

Optimal control of molecular motion: design, implementation, and inversion.

This paper reviews recent theoretical and experimental developments aimed at controlling molecular motion using tailored laser fields. Emphasis is given to seeking optimal designs for the laser controls and optimal implementation of the controls in the laboratory. Optimization on both counts provides a rigorous, flexible, and physically attractive means for obtaining the best possible control over molecular motion under any specified conditions. The theoretical design and laboratory implementation of control are best effected by a closed-loop process that draws on observations of the evolving molecular sample to steer it toward the desired target. Going beyond control, similar closed-loop laboratory learning concepts may lead to automated molecular monitors for inversion to systematically identify details of molecular Hamiltonians.

Chemistry, Physical↗
PubMed2000

Delignification of maize stems by peroxymonosulfuric acid, peroxyformic acid, peracetic acid, and hydrogen peroxide. 1. Physicochemical and structural characterization of the solubilized lignins.

Water-treated maize stems were subjected to delignification with peroxymonosulfuric acid at 20 degrees C for 144 h, with peroxyformic acid at 80 degrees C for 6 h, with peracetic acid at 50 degrees C for 6 h, and with 2% hydrogen peroxide at 45 degrees C for 12 h at pH 1.5, 4.4, 9.5, 11.5, 12.0, and 12.6, respectively, which solubilized 47.1, 91.3, 33.3, 16.6, 15.9, 17.4, 86.2, 87.7, and 91. 3% of the original lignin, respectively. Substantial lignins were released during the treatment with peroxyformic acid and hydrogen peroxide at pH > or =11.5, whereas an insignificant effect on delignification was observed by using peroxymonosulfuric acid, peracetic acid, and hydrogen peroxide under acidic, natural, and weakly alkaline media conditions. The structures of the isolated lignin preparations were investigated by chemical analysis, gel permeation chromatography, and UV, FT-IR, and (13)C NMR spectroscopy.

Formates↗
PubMed2000

Selection and application of peptide-binding peptides.

Peptide-binding ligands would be useful for directing reagents to particular epitopes in a protein, the detection of peptide hormones, and many other applications. Here we show that peptides of modest size isolated from a library using a simple genetic assay can act as specific receptors for other peptides. The equilibrium dissociation constants of these peptide-peptide complexes are higher than those of typical monoclonal antibody-epitope complexes. Nonetheless, as shown here, these peptide-binding peptides can be used to detect or purify proteins containing the partner peptide.

Amino Acid Sequence↗
PubMed2000

Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities.

INTRODUCTION: Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice. Because expression of Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Purkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of deficiencies in Cx40. METHODS AND RESULTS: Ten Cx40-/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40-/- mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6+/-6.4 msec vs 36.0+/-4.1 msec, P = 0.002). Not only the HV interval (14.0+/-3.0 msec vs 10.4+/-1.2 msec, P = 0.003) but also the AH interval (33.2+/-4.8 msec vs 27.1+/-3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40-/- compared with Cx40+/+ mice. CONCLUSION: Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction.

Animals↗
PubMed2000

Transcatheter closure of multiple atrial septal defects. Initial results and value of two- and three-dimensional transoesophageal echocardiography.

AIMS: To examine the feasibility of transcatheter closure of multiple atrial septal defects using two Amplatzer devices simultaneously and to describe the importance and the role of two- and three-dimensional transoesophageal echocardiography in the selection and closure of such defects. METHODS: Twenty-two patients with more than one atrial septal defect underwent an attempt at transcatheter closure of their atrial septal defects at a mean+/-SD age of 30. 8+/-18.6 years (range 3.7-65.9 years) and mean weight of 56.6+/-25.5 kg (range 12.9-99 kg) using two Amplatzer devices implanted simultaneously via two separate delivery systems. During catheterization, two dimensional transoesophageal echocardiography was performed in all but one patient, during and after transcatheter closure, while three dimensional transoesophageal echocardiography was performed in six patients before and after transcatheter closure. RESULTS: Forty-four devices were deployed in all patients to close 45 defects (one patient with three defects closed by two devices). Two dimensional transoesophageal echocardiography was helpful in selection and in guiding correct deployment of the devices. The mean size of the larger defect, as measured by transoesophageal echocardiography was 12.8+/-5.9 mm and the mean size of the smaller defect was 6.6+/-3.0 mm. The mean size of the larger devices was 15+/-7.5 mm, and 8.4+/-3.7 mm for the smaller. Three dimensional transoesophageal echocardiography provided superior imaging and demonstrated the number, shape and the surrounding structures of the atrial septal defects in one single view. The median fluoroscopy time was 28.7 min. Device embolization with successful catheter retrieval occurred in one patient. Forty-four devices were evaluated by colour Doppler transoesophageal echocardiography immediately after the catheterization with a successful closure rate of 97.7%. On follow-up colour Doppler transthoracic echocardiography demonstrated successful closure in 97.5% at 3 months. CONCLUSIONS: The use of more than one Amplatzer septal occluder to close multiple atrial septal defects is safe and effective. The use of two- and three-dimensional transoesophageal echocardiography provided useful information for transcatheter closure of multiple atrial septal defects using two devices. Three-dimensional transoesophageal echocardiography enhanced our ability to image and understand the spatial relationship of the atrial septal defect anatomy.

Adolescent↗
PubMed2000

Multiple-objective designs in a dose-response experiment.

This article is an extension of the work of Huang and Wong (1), who found dual-objective designs for models with a continuous outcome. We consider quantal dose-response experiments with a binary outcome and develop multiple-objective designs for two or more Bayesian optimality criteria. Using the logit model as an illustrative example, we construct numerically optimal designs for estimating model parameters and percentiles, with possibly unequal interest in each of the objectives. We also show that the popular equal dosage assignment rule can be a rather inefficient design for estimating model parameters under a Bayesian setup.

Bayes Theorem↗
PubMed2000

Optimal spliced alignment of homologous cDNA to a genomic DNA template.

MOTIVATION: Supplementary cDNA or EST evidence is often decisive for discriminating between alternative gene predictions derived from computational sequence inspection by any of a number of requisite programs. Without additional experimental effort, this approach must rely on the occurrence of cognate ESTs for the gene under consideration in available, generally incomplete, EST collections for the given species. In some cases, particular exon assignments can be supported by sequence matching even if the cDNA or EST is produced from non-cognate genomic DNA, including different loci of a gene family or homologous loci from different species. However, marginally significant sequence matching alone can also be misleading. We sought to develop an algorithm that would simultaneously score for predicted intrinsic splice site strength and sequence matching between the genomic DNA template and a related cDNA or EST. In this case, weakly predicted splice sites may be chosen for the optimal scoring spliced alignment on the basis of surrounding sequence matching. Strongly predicted splice sites will enter the optimal spliced alignment even without strong sequence matching. RESULTS: We designed a novel algorithm that produces the optimal spliced alignment of a genomic DNA with a cDNA or EST based on scoring for both sequence matching and intrinsic splice site strength. By example, we demonstrate that this combined approach appears to improve gene prediction accuracy compared with current methods that rely only on either search by content and signal or on sequence similarity. AVAILABILITY: The algorithm is available as a C subroutine and is implemented in the SplicePredictor and GeneSeqer programs. The source code is available via anonymous ftp from ftp. zmdb.iastate.edu. Both programs are also implemented as a Web service at http://gremlin1.zool.iastate.edu/cgi-bin/s p.cgiand http://gremlin1.zool.iastate.edu/cgi-bin/g s.cgi, respectively. CONTACT: vbrendel@iastate.edu

Algorithms↗
PubMed2000

Use of heme compounds as iron sources by pathogenic neisseriae requires the product of the hemO gene.

Heme compounds are an important source of iron for neisseriae. We have identified a neisserial gene, hemO, that is essential for heme, hemoglobin (Hb), and haptoglobin-Hb utilization. The hemO gene is located 178 bp upstream of the hmbR Hb receptor gene in Neisseria meningitidis isolates. The product of the hemO gene is homologous to enzymes that degrade heme; 21% of its amino acid residues are identical, and 44% are similar, to those of the human heme oxygenase-1. DNA sequences homologous to hemO were ubiquitous in commensal and pathogenic neisseriae. HemO genetic knockout strains of Neisseria gonorrhoeae and N. meningitidis were unable to use any heme source, while the assimilation of transferrin-iron and iron-citrate complexes was unaffected. A phenotypic characterization of a conditional hemO mutant, constructed by inserting an isopropyl-beta-D-thiogalactopyranoside (IPTG)-regulated promoter upstream of the ribosomal binding site of hemO, confirmed the indispensability of the HemO protein in heme utilization. The expression of HemO also protected N. meningitidis cells against heme toxicity. hemO mutants were still able to transport heme into the cell, since both heme and Hb could complement an N. meningitidis hemA hemO double mutant for growth. The expression of the HmbR receptor was reduced significantly by the inactivation of the hemO gene, suggesting that hemO and hmbR are transcriptionally linked. The expression of the unlinked Hb receptor, HpuAB, was not altered. Comparison of the polypeptide patterns of the wild type and the hemO mutant led to detection of six protein spots with an altered expression pattern, suggesting a more general role of HemO in the regulation of gene expression in Neisseriae.

Amino Acid Sequence↗
PubMed2000

Degradation of heme in gram-negative bacteria: the product of the hemO gene of Neisseriae is a heme oxygenase.

A full-length heme oxygenase gene from the gram-negative pathogen Neisseria meningitidis was cloned and expressed in Escherichia coli. Expression of the enzyme yielded soluble catalytically active protein and caused accumulation of biliverdin within the E. coli cells. The purified HemO forms a 1:1 complex with heme and has a heme protein spectrum similar to that previously reported for the purified heme oxygenase (HmuO) from the gram-positive pathogen Corynebacterium diphtheriae and for eukaryotic heme oxygenases. The overall sequence identity between HemO and these heme oxygenases is, however, low. In the presence of ascorbate or the human NADPH cytochrome P450 reductase system, the heme-HemO complex is converted to ferric-biliverdin IXalpha and carbon monoxide as the final products. Homologs of the hemO gene were identified and characterized in six commensal Neisseria isolates, Neisseria lactamica, Neisseria subflava, Neisseria flava, Neisseria polysacchareae, Neisseria kochii, and Neisseria cinerea. All HemO orthologs shared between 95 and 98% identity in amino acid sequences with functionally important residues being completely conserved. This is the first heme oxygenase identified in a gram-negative pathogen. The identification of HemO as a heme oxygenase provides further evidence that oxidative cleavage of the heme is the mechanism by which some bacteria acquire iron for further use.

Amino Acid Sequence↗
PubMed2000

Identification of two novel hrp-associated genes in the hrp gene cluster of Xanthomonas oryzae pv. oryzae.

We have cloned a hrp gene cluster from Xanthomonas oryzae pv. oryzae. Bacteria with mutations in the hrp region have reduced growth in rice leaves and lose the ability to elicit a hypersensitive response (HR) on the appropriate resistant cultivars of rice and the nonhost plant tomato. A 12,165-bp portion of nucleotide sequence from the presumed left end and extending through the hrpB operon was determined. The region was most similar to hrp genes from Xanthomonas campestris pv. vesicatoria and Ralstonia solanacearum. Two new hrp-associated loci, named hpa1 and hpa2, were located beyond the hrpA operon. The hpa1 gene encoded a 13-kDa glycine-rich protein with a composition similar to those of harpins and PopA. The product of hpa2 was similar to lysozyme-like proteins. Perfect PIP boxes were present in the hrpB and hpa1 operons, while a variant PIP box was located upstream of hpa2. A strain with a deletion encompassing hpa1 and hpa2 had reduced pathogenicity and elicited a weak HR on nonhost and resistant host plants. Experiments using single mutations in hpa1 and hpa2 indicated that the loss of hpa1 was the principal cause of the reduced pathogenicity of the deletion strain. A 1,519-bp insertion element was located immediately downstream of hpa2. Hybridization with hpa2 indicated that the gene was present in all of the strains of Xanthomonas examined. Hybridization experiments with hpa1 and IS1114 indicated that these sequences were detectable in all strains of X. oryzae pv. oryzae and some other Xanthomonas species.

Amino Acid Sequence↗
PubMed2000

Nitric oxide modulates fracture healing.

The role of the messenger molecule nitric oxide has not been evaluated in fracture healing. NO is synthesized by three kinds of nitric oxide synthase (NOS): inducible NOS (iNOS), endothelial (eNOS), and neuronal (bNOS). We evaluated the role of these enzymes in a rat femur fracture-healing model. There was no messenger RNA (mRNA) expression, immunoreactivity, or enzymatic activity for NOS in unfractured femoral cortex. After fracture, however, mRNA, protein, and enzymatic activity for iNOS were identified in the healing rat femoral fracture callus, with maximum activity on day 15. The mRNA expression for eNOS and bNOS was induced slightly later than for iNOS, consistent with a temporal increase in calcium-dependent NOS activity that gradually increased up to day 30. mRNA expression for the three NOS isoforms also was found in six of six human fracture callus samples. To study the effect of suppression of NO synthesis on fracture healing, an experimental group of rats was fed an NOS inhibitor, L-nitroso-arginine methyl ester (L-NAME), and the control group was fed its inactive enantiomer, D-nitroso-arginine methyl ester (D-NAME). An 18% (p < or = 0.01) decrease in cross-sectional area and a 45% (p < or = 0.05) decrease in failure load were observed in the NOS-inhibited group on day 24 after fracture. Furthermore, the effect of NO supplementation to fracture healing was studied by delivering NO to the fracture site using carboxybutyl chitosan NONOate locally. On day 17 after fracture, there was a 30% (p < or = 0.05) increase in cross-sectional area in the NO-donor group compared with the NOS inhibition group. These results show for the first time that NO is expressed during fracture healing in rats and in humans, that suppression of NOS impairs fracture healing, and that supplementation of NO can reverse the inhibition of healing produced by NOS inhibitors.

Animals↗
PubMed2000

Chronic toxicity of rare-earth elements on human beings: implications of blood biochemical indices in REE-high regions, South Jiangxi.

Blood analyses for rare-earth element (REE)-high background regions in South Jiangxi show that the population averages of many of the biochemical indices deviate markedly from normal values in the normal region. These deviations are thought to be caused by prolonged intake of REE through food chains in view of that the toxicity of other harmful metals such as Pb and Cd can be neglected because of their insignificant amounts in the environment. In comparison with the normal region, blood biochemical indices abnormal in the REE-high regions are manifested as low total serum protein (TSP), albumin, beta-globulin, glutamic pyruvic transitanase, serium triglycerides, and immunoglobulin, but high cholesterol. These deviations may be related to the REE concentration and composition of food chains, and are sex dependent. Certain blood indices (such as TSP) of different age groups in the LREE-high region indicate that the influence of REE on males is a one-way irreversible process, whereas females show a strong ability of restoration.

Adult↗
PubMed2000

Rare-earth element distribution characteristics of biological chains in rare-earth element-high background regions and their implications.

The rare-earth element (REE) contents of water and vegetables from two typical REE-high background regions and a normal region in Gannan, Jiangxi Province, indicated that the REE contents were significantly different from those of water and vegetables, respectively. The average values are 0.03 mg/L and 0.11 mg/L REE for water from regions A and B. As the REE contents of vegetables from region A are different from region B, it is suggested that there are a number of factors controlling the REE distribution from those among plants. By comparing with the normal region, the soluble REE contents of water from the REE-high background regions are higher than those of the normal region by factors of 18 and 68, respectively. The REE contents of most plants and crops from regions A and B are higher than those of the normal region. It is clear that the REEs are the indispensable elements of plants during their growing period. Why are the REE contents of some plants from regions A and B usually higher than those from the normal region? The answer is that the plants and crops have passively absorbed REE during their growth.

China↗
PubMed2000

Bacteriostatic effects of cerium-humic acid complex: an experimental study.

The bacteriostatic potency of the cerium-humic acid complex was evaluated by experimental measurement of this complex interaction with E. coli, Bacillus pyocyaneus, Staphylococcus aureus, Leuconostoc and Streptococcus faecalis, and by comparison bacteriostatic effects with the cerium-citrate complex. The experimental results indicated that the cerium-humic acid complex strongly inhibited growth of all five bacterial strains, and its diameter of bacteriostatic circles were more than 30 mm. The minimal bacteria-inhibiting concentration were 1 x 10(-3), 2 x 10(-3) and 1 x 10(-2) mol/L for E. coli and Bacillus pyocyaneus, Staphylococcus aureus, and Leuconostoc and Streptococcus faecalis individually, and the measured minimal bactericidal concentrations were 2 x 10(-3) and 1 x 10(-2) mol/L for Bacillus pyocyaneus, E. coli, and Leuconostoc. To kill Staphylococcus aureus and Streptococcus faecalis, the concentration had to be more than 1 x 10(-20 mol/L. On the contrary, we found that cerium-citrate complex did not inhibit the growth of the above five bacteria, but stimulated bacterial growth. The completely different bacteriostatic results of two cerium complexes may hint that the association and chemical properties of the two complexes were different.

Anti-Bacterial Agents↗
PubMed2000

Oxidized lipoproteins and endothelium.

Endothelium is an early target of pro-atherosclerotic events, which may result in functional and morphological perturbations. Oxidized low density lipoproteins, an atherogenic factor with strong cytotoxicity, may potentially contribute to altered endothelial function through the activation of a stress response, which would rescue cells to full vitality, or, conversely, by leading to cell death. Evidence is presented here for the ability of chemically oxidized low density lipoproteins to induce the synthesis of the inducible form of heat shock protein 70 in cultured human endothelial cells, and for the association of epitopes of these modified lipoproteins with apoptotic endothelial cells in aortic sections from hypercholesterolemic rabbits.

Animals↗