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Biomedical subjects

R Zhang

Publications and source records attributed to R Zhang.

At least 55 records · Page 3Linked to original sources
PubMed2001

Highly efficient asymmetric epoxidation of alkenes with a D(4)-symmetric chiral dichlororuthenium(IV) porphyrin catalyst.

A dichlororuthenium(IV) complex of 5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,2:5,8-dimethanoanthrance-9-yl]porphyrin, [Ru(IV)(D(4)-Por)Cl(2)] (1), was prepared by heating [Ru(II)(D(4)-Por)(CO)(MeOH)] (2) in refluxing CCl(4). Complex 1 is characterized by (1)H NMR (paramagnetically shifted pyrrolic protons at delta(H) = -52.3 ppm), FAB-mass spectroscopies, and magnetic susceptibility measurement (mu(eff) = 3.1 mu(B)). The ruthenium complex exhibits remarkable catalytic activity toward enantioselective alkene epoxidation using 2,6-dichloropyridine N-oxide (Cl(2)pyNO) as terminal oxidant. The Ru(IV)-catalyzed styrene epoxidation is achieved within 2 h (versus 48 h for the 2-catalyzed reaction), and optically active styrene oxide was obtained in 69% ee and 84% yield (875 turnovers). Likewise, substituted styrenes and some conjugated cis-disubstituted alkenes (e.g., cis-beta-methylstyrene, cis-1-phenyl-3-penten-1-yne, 1,2-dihydronaphthalene, and 2,2-dimethylchromenes) are converted effectively to their organic epoxides in 50-80% ee under the Ru(IV)-catalyzed conditions, and more than 850 turnovers of epoxides have been attained. When subjecting 1 to four repetitive uses by recharging the reaction mixture with Cl(2)pyNO and styrene, styrene oxide was obtained in a total of 2190 turnovers and 69% ee. UV-vis and ESI-mass spectral analysis of the final reaction mixture revealed that a ruthenium-carbonyl species could have been formed during the catalytic reaction, leading to the apparent catalyst deactivation. We prepared a heterogeneous chiral ruthenium porphyrin catalyst by immobilizing 1 into sol-gel matrix. The heterogeneous catalyst is highly active toward asymmetric styrene epoxidation producing styrene oxide in 69% ee with up to 10,800 turnovers being achieved. The loss of activity of the Ru/sol-gel catalyst is ascribed to catalyst leaching and/or deactivation. On the basis of Hammett correlation (rho(+) = -1.62, R = 0.99) and product analysis, a dioxoruthenium(VI) porphyrin intermediate is not favored.

Alkenes↗
PubMed2001

Association between myeloperoxidase levels and risk of coronary artery disease.

CONTEXT: Myeloperoxidase (MPO), a leukocyte enzyme that promotes oxidation of lipoproteins in atheroma, has been proposed as a possible mediator of atherosclerosis. OBJECTIVE: To determine the association between MPO levels and prevalence of coronary artery disease (CAD). DESIGN, SETTING, AND PATIENTS: Case-control study conducted from July to September 2000 in a US tertiary care referral center, including 158 patients with established CAD (cases) and 175 patients without angiographically significant CAD (controls). MAIN OUTCOME MEASURES: Association of MPO levels per milligram of neutrophil protein (leukocyte-MPO) and MPO levels per milliliter of blood (blood-MPO) with CAD risk. RESULTS: Leukocyte- and blood-MPO levels were both significantly greater in patients with CAD than in controls (P<.001). In multivariable models adjusting for traditional cardiovascular risk factors, Framingham risk score, and white blood cell counts, MPO levels were significantly associated with presence of CAD, with an OR of 11.9 (95% CI, 5.5-25.5) for the highest vs lowest quartiles of leukocyte-MPO and an OR of 20.4 (95% CI, 8.9-47.2) for the highest vs lowest quartiles of blood-MPO. CONCLUSIONS: Elevated levels of leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.

Aged↗
PubMed2001

Fractionation of isotopically labeled peptides in quantitative proteomics.

The goal of quantitative proteomics is to examine the expression levels of all of the proteins in a biological system and recognize those that change as a function of some stimulus. Quantification is now frequently based on derivatization of peptides with isotopically distinguishable labeling agents. This study examines the extent to which isotopic forms of peptides having the same amino acid sequence are resolved by reversed-phase chromatography and assesses the degree to which resolution of these isotopically different forms of a peptide impact quantification. Three derivatizing agents were examined, the do and d3 forms of N-acetoxysuccinimide, the do and d4 forms of succinic anhydride, and the do and d8 forms of the commercial ICAT reagent Peptide mixtures from control and experimental samples were derivatized individually, mixed, subjected to reversed-phase chromatography, and analyzed by ESI-MS. When partial resolution of the isotopic forms of a peptide occurs, the largest error in assessing the true isotope ratio in a sample occurs when sampling at the extremes of a peak. Early in the elution of a peak, the sample will be enriched in the deuterated species, whereas the opposite is true at the tailing edge of a peak. Acetylated peptides showed the lowest degree of separation. Resolution of the deuterated and nondeuterated forms in this case was 0.023. This amounts to slightly over a 1-s difference in their peak maxima and can cause a typical error of +/- 6% at the leading and tailing edges of a peak. In contrast, resolution of the deuterated and nondeuterated forms of the ICAT reagent were calculated to be 0.45. This means that in a peak of 1-min width (W1/2), the peak maxima will vary by approximately 30 s, and measurement errors of -83 and +500% can occur at the leading and tailing edges of a peak. It is concluded that resolution of isotopic forms of a peptide can cause substantial quantification errors in quantitative proteomics.

Angiotensin I↗
PubMed2001

Interaction of corticotropin-releasing factor and glucagon-like peptide-1 on behaviors in chicks.

Both corticortropin-releasing factor (CRF) and glucagon-like peptide-1 (GLP-1) inhibit food intake of chicks, but they also produce other behaviors. The present experiments were undertaken to clarify the interaction of CRF and GLP-1 regarding their anorectic actions as well as other behaviors. In Experiment 1, birds were injected intracerebroventricularly (i.c.v.), following a 3-h fast, with either saline, 0.1 microg of CRF, 0.1 microg of CRF+0.1 microg of GLP-1 or 0.1 microg of CRF+1 microg of GLP-1, and food intake was measured for 2 h. The injection of CRF decreased food intake, and CRF injected with GLP-1 suppressed food intake for up to 2 h. Birds were treated similarly in Experiment 2 in which the doses of CRF and GLP-1 were reversed. GLP-1 strongly suppressed food intake, and this effect was augmented by coadministration of CRF. In Experiment 3, the behaviors of chicks injected with saline, CRF (0.1 microg), GLP-1 (0.1 microg) or CRF (0.1 microg)+GLP-1 (0.1 microg) were monitored for the numbers of steps, vocalization and locomotion. Chicks were excited, moved more and vocalized loudly following injection of CRF, whereas an opposite response was seen with GLP-1. The behaviors were intermediate following the coinjection of the two peptides. In conclusion, CRF and GLP-1 interact in the chick brain, but the response depends on the behavior being measured.

Animals↗
PubMed2001

Microtubular architecture of biodegradable polymer scaffolds.

It is a relatively new approach to generate tissues with mammalian cells and scaffolds (temporary synthetic extracellular matrices). Many tissues, such as nerve, muscle, tendon, ligament, blood vessel, bone, and teeth, have tubular or fibrous bundle architectures and anisotropic properties. In this work, we have designed and fabricated highly porous scaffolds from biodegradable polymers with a novel phase-separation technique to generate controllable parallel array of microtubular architecture. Porosity as high as 97% has been achieved. The porosity, diameter of the microtubules, the tubular morphology, and their orientation are controlled by the polymer concentration, solvent system, and temperature gradient. The mechanical properties of these scaffolds are anisotropic. Osteoprogenitor cells are seeded in these three-dimensional scaffolds and cultured in vitro. The cell distribution and the neo-tissue organization are guided by the microtubular architecture. The fabrication technique can be applied to a variety of polymers, therefore the degradation rate and cell--matrix interactions can be controlled by the chemical composition of the polymers and the incorporation of bioactive moieties. These microtubular scaffolds may be used to engineer a variety of tissues with anisotropic architecture and properties.

Animals↗
PubMed2001

Suppression of food intake induced by corticotropin-releasing factor family in neonatal chicks.

Corticotropin-releasing factor (CRF), urocortin and urotensin I share amino acid sequences, and they inhibit food intake in mammals. CRF plays a potent role in decreasing food intake in avian species, but the effects of urocortin and urotensin I have not been investigated. Therefore, the effect of these three peptides on food intake in the neonatal chick was compared. In Experiment 1, birds were injected intracerebroventricularly (i.c.v.) with either 0, 0.01, 0.1 or 1 microg of urocortin following a 3-h fast, and food intake was measured for 2 h post-injection. Food intake was suppressed in a dose-dependent manner. Using a similar design in Experiment 2, the effect of urotensin I was investigated. Urotensin I appeared to suppress food intake in neonatal chicks more than urocortin did. In Experiment 3, the efficacy of CRF, urocortin and urotensin I was directly compared using one dose, 0.1 microg. The results indicated that the suppressive effect on food intake was strongest for CRF followed by urotensin I, then urocortin. These results suggest that the structure of receptors for the CRF family in chicks may be somewhat different than in mammals.

Animals↗
PubMed2001

Crystal structure of the extracellular segment of integrin alpha Vbeta3.

Integrins are alphabeta heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands. We have solved the crystal structure of the extracellular portion of integrin alphaVbeta3 at 3.1 A resolution. Its 12 domains assemble into an ovoid "head" and two "tails." In the crystal, alphaVbeta3 is severely bent at a defined region in its tails, reflecting an unusual flexibility that may be linked to integrin regulation. The main inter-subunit interface lies within the head, between a seven-bladed beta-propeller from alphaV and an A domain from beta3, and bears a striking resemblance to the Galpha/Gbeta interface in G proteins. A metal ion-dependent adhesion site (MIDAS) in the betaA domain is positioned to participate in a ligand-binding interface formed of loops from the propeller and betaA domains. MIDAS lies adjacent to a calcium-binding site with a potential regulatory function.

Amino Acid Motifs↗
PubMed2001

Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule.

The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described. The crystal structure of a complex containing the human CD4 N-terminal two-domain fragment and the murine I-A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the "top corner" of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side chain extends into a hydrophobic concavity formed by MHC residues from both alpha 2 and beta 2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals that the complex appears V-shaped with the membrane-proximal pMHCII at the apex. This configuration excludes a direct TCR-CD4 interaction and suggests how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the pMHCII-binding site on CD4, contributing to immunodeficiency.

Amino Acid Sequence↗
PubMed2001

A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.

OBJECTIVE: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD. METHODS: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. RESULTS: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population. CONCLUSION: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.

Aged↗
PubMed2001

Calmodulin-binding protein BP-10, a probable new member of plant nonspecific lipid transfer protein superfamily.

CaMBP-10 is a novel plant endogenous calmodulin-binding protein with important physiological functions. The partial cDNA sequence of this protein was cloned using RT-PCR. The deduced peptide (designated PCBP10) is composed of 74 amino acid residues containing a basic amphiphilic alpha-helix typical for calmodulin-binding proteins. PCBP10 shows very high amino acid sequence homology with plant nonspecific lipid-transfer proteins (nsLTPs). Sequence analysis also reveals that PCBP10 has similar amino acid composition to plant nsLTPs, and seven of the eight conserved cysteine residues are found in PCBP10. Furthermore, the secondary structure features of PCBP10 are very similar to those of plant nsLTPs. In addition, there are striking resemblances between CaMBP-10 and plant nsLTPs in their biochemical and physical properties. Our results suggest that CaMBP-10 is a novel member of the plant and nsLTP gene family, and the Ca(2+)/CaM regulative system may also play roles in lipid metabolism, defense reactions, and the adaptation of plants to natural environment.

Base Sequence↗
PubMed2001

A refined accuracy index to evaluate algorithms of protein secondary structure prediction.

Nowadays even a 1% increase of the accuracy for the secondary structure prediction is considered remarkable progress. In this case, we have to consider the reasonableness of the accuracy index Q3, which is used widely. A refined accuracy index, called Q8, is proposed to evaluate algorithms of secondary structure prediction. It is shown that Q8 is superior to the widely used index Q3 in that the former carries more information of the predictive accuracy matrix than does the latter. Therefore, algorithms are evaluated more objectively by Q8 than Q3. Based on 396 nonhomologous proteins, five currently available algorithms of secondary structure prediction were evaluated and compared using the new index Q8. Of the five algorithms, PHD turned out to be the unique algorithm, with Q8 accuracy better than 70%. It is suggested that Q3 should be replaced by Q8 in evaluating secondary structure prediction in future studies.

Algorithms↗
PubMed2001

A picoliter-volume mixer for microfluidic analytical systems.

Mixing confluent liquid streams is an important, but difficult operation in microfluidic systems. This paper reports the construction and characterization of a 100-pL mixer for liquids transported by electroosmotic flow. Mixing was achieved in a microfabricated device with multiple intersecting channels of varying lengths and a bimodal width distribution. All channels running parallel to the direction of flow were 5 microm in width whereas larger 27-microm-width channels ran back and forth through the parallel channel network at a 45 degrees angle. The channel network composing the mixer was approximately 10 microm deep. It was observed that little mixing of the confluent solvent streams occurred in the 100-microm-wide, 300-microm-long mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, after passage through the channel network in the approximately 200-microm-length static mixer bed, mixing was complete as determined by confocal microscopy and CCD detection. Theoretical simulations were also performed in an attempt to describe the extent of mixing in microfabricated systems.

Algorithms↗
PubMed2001

Effect of naturally occurring active site mutations on hepatitis C virus NS3 protease specificity.

A comparison of the DNA sequences from all available genotypes of HCV indicate that the active site residues of the NS3 protease are strictly conserved with the exception of positions 123 and 168, which border the S(4) subsite. In genotype 3, the canonic arginine and aspartic acid have been replaced with threonine and glutamine, respectively. To determine if these differences contribute to an altered specificity, we characterized single-chain NS3 proteases from strains 1a, 1b, and 3a with peptide substrates and product inhibitors on the basis of the natural cleavage junction sequences, in addition to polyprotein substrates derived from the 1a strain. No statistically significant differences in specificity were observed. To demonstrate that the active sites were actually different, we generated and evaluated peptide substrates with unnatural extended side-chains. These studies confirmed that there are measurable differences between the NS3 proteases of genotypes 1 and 3. Specifically, a 5-fold difference in K(i) was observed between the proteases from genotypes 1 and 3 when a D-Glu occupied P(5), and a 30-fold difference was seen when this position contained a D-homoglutamate. The contribution of residues 123 and 168 toward the altered specificity was then evaluated individually by site-directed mutagenesis. These mutants showed that potency differences within this series could be attributed to the residue that occupied position 123 of the protease. Modeling these unnatural substrate/mutant protease interactions, on the basis of cocrystal structures of enzyme-substrate complexes, provides a structural basis for these observations. Proteins 2001;43:82-88.

Binding Sites↗
PubMed2001

Effective volumetric lattice Boltzmann scheme.

An efficient fractional volumetric scheme is proposed for lattice Boltzmann method (LBM). By reducing the effective time step, the scheme possesses much better stability particularly for thermal LBM. The same accuracy and simplicity of the standard LBM are preserved for achieving the Navier-Stokes equation. Since the effective viscosity is reduced by the fraction factor p, the scheme becomes very effective for simulating high Reynolds number thermal flows.

Journal Article↗
PubMed2001

Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity.

Myotonic dystrophy protein kinase (DMPK) and Rho-kinase are related. An important function of Rho-kinase is to phosphorylate the myosin-binding subunit of myosin phosphatase (MYPT1) and inhibit phosphatase activity. Experiments were carried out to determine if DMPK could function similarly. MYPT1 was phosphorylated by DMPK. The phosphorylation site(s) was in the C-terminal part of the molecule. DMPK was not inhibited by the Rho-kinase inhibitors, Y-27632 and HA-1077. Several approaches were taken to determine that a major site of phosphorylation was T654. Phosphorylation at T654 inhibited phosphatase activity. Thus both DMPK and Rho-kinase may regulate myosin II phosphorylation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

[Breath drive response of COPD patients with hypercapnic respiratory failure and their families].

OBJECTIVE: To investigate the breath drive response of COPD patients and their offspring and to analyze the potential heredity. METHODS: P(0.1) and ventilatory response to hypoxia (DeltaV(E)/DeltaSaO(2)), P(0.1) response to hypoxia (DeltaP(0.1)/DeltaSaO(2)), P(0.1) response to hypercapnia (DeltaP(0.1)/DeltaP(ET)CO(2)DeltaV(E)/P(ET)CO(2)) and ventilatory response to hypercapnia (DeltaV(E)/P(ET)CO(2)) were measured in 6 COPD patients with type II respiratory failure and in 21 of their normal adult offspring. RESULTS: (1) P(0.1) was remarkably higher among all of the COPD patients than among their offspring and normal controls. The hypoxia response (DeltaP(0.1)/DeltaSaO(2)) and DeltaP(0.1)/DeltaP(ET)CO(2) were significantly decreased among the COPD patients (P < 0.05). (2) The hypoxia response was low among 10 of the offspring of COPD patients, and was normal among the other 11. (3) The ventilatory response to hypercapnia (DeltaV(E)/DeltaP(ET)CO(2)) was significantly decreased among the COPD patients, and varied greatly among their offspring. CONCLUSION: (1) The depression of respiratory responses to hypoxia and hypercapnia may be the reason of type II respiratory failure. (2) The depression of hypoxia response may be influenced by genetic factors.

Adult↗
PubMed2001

Thickness-dependent Curie temperatures of ultrathin magnetic films: effect of the range of spin-spin interactions.

We present a simple model of spin-spin coupling which provides insight into the nature of the rapid decrease in the Curie temperature with decreasing thin film thickness n (number of monolayers). The shift of Curie temperature t(n) = 1-T(c)(n)/T(c)(infinity) follows the usual power law t(n) approximately n(-lambda) in thin films crossing over to linear behavior t(n) approximately n in the ultrathin film thickness limit. Experimental results for ferromagnetic thin films are compared, and shown to follow curves of t(n) with lambda values dependent on the nature of the spin-spin interactions.

Journal Article↗