Biomedical subjects

H Zheng

Publications and source records attributed to H Zheng.

At least 19 recordsLinked to original sources

PubMed2006

Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults.

BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children. OBJECTIVES: To investigate the application of self-expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short-term results. METHODS: 29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow-up evaluation of the treatment within 1 day, 1 month and 3-6 months after successful closure. RESULTS: 20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7-99.1%) during inhalation of oxygen. In group 1, the dimensions of the left atrium, left ventricle and pulmonary artery increased considerably in 3-6-months of follow-up compared with those of preocclusion. CONCLUSIONS: Transcatheter closure is an effective treatment for adults with PDA associated with reversible severe pulmonary arterial hypertension. Further research is needed for the evaluation of long-term results.

Adolescent↗

PubMed2006

Quasiparticlelike peaks, kinks, and electron-phonon coupling at the (pi,0) regions in the CMR oxide La2-2x Sr1+2x Mn2 O7.

Using angle-resolved photoemission, we have observed sharp quasiparticlelike peaks in the prototypical layered manganite La(2-2x)Sr(1+2x)Mn(2)O(7) (x=0.36,0.38). We focus on the (pi,0) regions of k space and study their electronic scattering rates and dispersion kinks, uncovering bilayer-split bands, the critical energy scales, momentum scales, and strengths of the interactions that renormalize the electrons. To identify these bosons, we measured phonon dispersions in the energy range of the kink by inelastic neutron scattering, finding a good match in both energy and momentum to the oxygen bond-stretching phonons.

Journal Article↗

PubMed2006

Protein disulfide isomerase assisted protein folding in malaria parasites.

In eukaryotes, the formation of protein disulfide bonds among cysteine residues is mediated by protein disulfide isomerases and occurs in the highly oxidised environment of the endoplasmic reticulum. This process is poorly understood in malaria parasites. In this paper, we report the gene isolation, sequence and phylogenetic comparisons, protein structure and thioredoxin-domain analyses of nine protein disulfide isomerases-like molecules from five species of malaria parasites including Plasmodium falciparum and Plasmodium vivax (human), Plasmodium knowlesi (simian) and Plasmodium berghei and Plasmodium yoelii (murine). Four of the studied protein disulfide isomerases belong to P. falciparum malaria and have been named PfPDI-8, PfPDI-9, PfPDI-11 and PfPDI-14, based on their chromosomal location. Among these, PfPDI-8 bears the closest similarity to a prototype PDI molecule with two thioredoxin domains (containing CGHC active sites) and a C-terminal Endoplasmic reticulum retrieval signal, SEEL. PfPDI-8 is expressed during all stages of parasite life cycle and is highly conserved (82-96% identity at amino acid level) in the other four Plasmodium species studied. Detailed biochemical analysis of PfPDI-8 revealed that this molecule is a potent oxido-reductase enzyme that facilitated the disulfide-dependent conformational folding of EBA-175, a leading malaria vaccine candidate. These studies open the avenues to understand the process of protein folding and secretory pathway in malaria parasites that in turn might aid in the production of superior recombinant vaccines and provide novel drug targets.

Amino Acid Sequence↗

PubMed2006

Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer's disease.

Brain iron dysregulation and its association with amyloid precursor protein (APP) plaque formation are implicated in Alzheimer's disease (AD) pathology and so iron chelation could be considered a rational therapeutic strategy for AD. Here we analyzed the effect of the main polyphenol constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), which possesses metal-chelating and radical-scavenging properties, on the regulation of the iron metabolism-related proteins APP and transferrin receptor (TfR). EGCG exhibited potent iron-chelating activity comparable to that of the prototype iron chelator desferrioxamine, and dose dependently (1-10 microm) increased TfR protein and mRNA levels in human SH-SY5Y neuroblastoma cells. Both the immature and full-length cellular holo-APP were significantly reduced by EGCG, as shown by two-dimensional gel electrophoresis, without altering APP mRNA levels, suggesting a post-transcriptional action. Indeed, EGCG suppressed the translation of a luciferase reporter gene fused to the APP mRNA 5'-untranslated region, encompassing the APP iron-responsive element. The finding that Fe(2)SO(4) reversed the action of EGCG on APP and TfR proteins reinforces the likelihood that these effects are mediated through modulation of the intracellular iron pool. Furthermore, EGCG reduced toxic beta-amyloid peptide generation in Chinese hamster ovary cells overexpressing the APP 'Swedish' mutation. Thus, the natural non-toxic brain-permeable EGCG may provide a potential therapeutic approach for AD and other iron-associated disorders.

Amyloid beta-Peptides↗

PubMed2006

First-order metal-insulator transitions in manganites: are they universal?

Conductivity data for La(2-2x)Sr(1+2xMn2O7 (x = 0.6) show a first-order transition from an orbital- or charge-ordered insulator to a metal as the temperature falls below approximately 160 K. The change in conductivity is 100 times larger than that seen previously in any single-phase manganite in zero field. The metallic low-temperature state is similar to x = 0.58, but x = 0.58 shows no evidence of orbital or charge order. This result supports a conclusion that strongly coupled magnetic-conductive transitions are first order.

Journal Article↗

PubMed2006

Nanomagnetic droplets and implications to orbital ordering in LA(1-x)Sr(x)CoO3.

Inelastic cold-neutron scattering on LaCoO3 provided evidence for a distinct low energy excitation at 0.6 meV coincident with the thermally induced magnetic transition. Coexisting strong ferromagnetic (FM) and weaker antiferromagnetic correlations that are dynamic follow the activation to the excited state, identified as the intermediate S = 1 spin triplet. This is indicative of dynamical orbital ordering favoring the observed magnetic interactions. With hole doping as in La(1-x)Sr(x)CoO3 , the FM correlations between Co spins become static and isotropically distributed due to the formation of FM droplets. The correlation length and condensation temperature of these droplets increase rapidly with metallicity due to the double exchange mechanism.

Journal Article↗

PubMed2006

M30, a novel multifunctional neuroprotective drug with potent iron chelating and brain selective monoamine oxidase-ab inhibitory activity for Parkinson's disease.

Iron and monoamine oxidase activity are increased in brain of Parkinson's disease (PD). They are associated with autoxidation and oxidative deamination of dopamine by MAO resulting in the generation of reactive oxygen species and the onset of oxidative stress to induce neurodegeneration. Iron chelators (desferal, Vk-28 and clioquinol) but not copper chelators have been shown to be neuroprotective in the 6-hydroxydoapmine and MPTP models of Parkinson's disease (PD), as are monoamine oxidase B inhibitors such as selegiline and rasagiline. These findings prompted the development of multifunctional anti PD drugs possessing iron chelating phamacophore of VK-28 and the propargylamine MAO inhibitory activity of rasagiline. M30 is a potent iron chelator, radical scavenger and brain selective irreversible MAO-A and B inhibitor, with little inhibition of peripheral MAO. It has neuroprotective activity in in vitro and in vivo models of PD and unlike selective MAO-B inhibitors it increases brain dopamine, serotonin and noradrenaline. These findings indicate beside its anti PD action, it may also possess antidepressant activity, similar to selective MAO-A and nonselective MAO inhibitors. These properties make it an ideal anti PD drug for which it is being developed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2006

Iron sucrose augments homocysteine-induced endothelial dysfunction in normal subjects.

Intravenous iron is commonly used in conjunction with erythropoietic agents to treat anemia in patients with chronic kidney disease. Iron has been proposed to promote oxidative stress and endothelial dysfunction in vascular tissues. We studied the acute effects of intravenous iron sucrose on homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects. In all, 40 healthy subjects received intravenous iron sucrose 100 mg or placebo over 30 min immediately before ingestion of 100 mg/kg of oral methionine in a double-blind, randomized study. Flow- and nitroglycerin-mediated dilation in the brachial artery, serum markers of iron stores, and homocysteine and nitrotyrosine levels were measured before and after study drug administration. Intravenous iron significantly increased transferrin saturation and non-transferrin-bound iron (NTBI) when compared with placebo. Flow-mediated dilation significantly decreased from baseline 1 h after administration of iron sucrose when compared with placebo (from 6.66+/-0.47 to 1.93+/-0.35% after iron sucrose vs from 6.00+/-0.40 to 5.61+/-0.46% after placebo, P<0.001), but did not differ between groups at 4 h (1.10+/-0.39 vs 1.33+/-0.51%). Nitroglycerin-mediated vasodilation, and homocysteine and 3-nitrotyrosine levels did not differ after administration of iron sucrose and placebo. Intravenous administration of iron sucrose in the setting of transient hyperhomocysteinemia induced by methionine ingestion significantly increased transferrin saturation and plasma levels of NTBI and significantly attenuated flow-mediated dilation in the brachial artery when compared with placebo. This potential mechanistic link between intravenous iron and endothelial dysfunction warrants further study of cardiovascular effects of intravenous iron in anemic chronic kidney disease populations.

Adult↗

PubMed2006

Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests for syphilis.

OBJECTIVES: To evaluate prospectively four rapid, point-of-care serological tests for syphilis in prenatal or high risk populations in four countries. METHODS: Tests were performed on consecutive clinic attenders, using whole blood in the clinic, and whole blood and serum in the laboratory. The sensitivity and specificity of each test was evaluated, using a standard treponemal test (Treponema pallidum haemagglutination assay (TPHA) or fluorescent treponemal antibody, absorbed (FTA-ABS) as gold standard. Non-treponemal tests (rapid plasma reagin (RPR) or venereal diseases research laboratory (VDRL) tests) were also performed on all subjects at three sites. RESULTS: The specificity of each rapid test was >95% at each site. Sensitivities varied from 64-100% and, in most cases, were lower when whole blood was used rather than serum. CONCLUSIONS: Rapid serological tests for syphilis are an acceptable alternative to conventional laboratory tests. Since they do not require equipment or electricity, they could increase coverage of syphilis screening, and enable treatment to be given at the first clinic visit.

Adolescent↗

PubMed2006

NMR characterization of recombinant transmembrane protein CB2 fragment CB2(180-233).

The expression of membrane proteins has been the bottleneck for their structural studies. Recently, we developed a method to obtain milligram quantities of isotope-labeled seven transmembrane G-protein coupled cannabinoid (CB) receptor fragment in E. coli. In order to verify this method and confirm the recombinant isotope-labeled CB2 fragment, 3D hetero-nuclear NMR techniques were used to analyze the structure of the fragment CB2(180-233) in DMSO-d6 solvent. The sequential assignments of TM5 and intra-cellular loop 3 were accomplished, which confirmed the experimental protocols of isotope-labeled recombinant protein expression, fusion protein cleavage, and membrane protein purification. The obtained structure also showed alpha-helix in the TM5 region, but it was interrupted by a disordered region (Gly204_ILe206). These results further revealed that our established approach is a promising method to express recombinant membrane proteins for their structural studies.

Amino Acid Sequence↗

PubMed2005

Nodal quasiparticle in pseudogapped colossal magnetoresistive manganites.

A characteristic feature of the copper oxide high-temperature superconductors is the dichotomy between the electronic excitations along the nodal (diagonal) and antinodal (parallel to the Cu-O bonds) directions in momentum space, generally assumed to be linked to the 'd-wave' symmetry of the superconducting state. Angle-resolved photoemission measurements in the superconducting state have revealed a quasiparticle spectrum with a d-wave gap structure that exhibits a maximum along the antinodal direction and vanishes along the nodal direction. Subsequent measurements have shown that, at low doping levels, this gap structure persists even in the high-temperature metallic state, although the nodal points of the superconducting state spread out in finite 'Fermi arcs'. This is the so-called pseudogap phase, and it has been assumed that it is closely linked to the superconducting state, either by assigning it to fluctuating superconductivity or by invoking orders which are natural competitors of d-wave superconductors. Here we report experimental evidence that a very similar pseudogap state with a nodal-antinodal dichotomous character exists in a system that is markedly different from a superconductor: the ferromagnetic metallic groundstate of the colossal magnetoresistive bilayer manganite La1.2Sr1.8Mn2O7. Our findings therefore cast doubt on the assumption that the pseudogap state in the copper oxides and the nodal-antinodal dichotomy are hallmarks of the superconductivity state.

Journal Article↗

PubMed2005

Electric field effect in diluted magnetic insulator anatase Co: TiO2.

An external electric field induced reversible modulation of a room temperature magnetic moment and coercive field is achieved in an epitaxial and insulating thin film of dilutely cobalt-doped anatase TiO2. This first demonstration of an electric field effect in any oxide-based diluted ferromagnet is realized in a high quality epitaxial heterostructure of PbZr(0.2)Ti(0.8)O(3)/Co: TiO(2)/SrRuO(3) grown on (001) LaAlO3. The observed effect, which is about 15% in strength in a given heterostructure, can be modulated over several cycles. Possible mechanisms for electric field induced modulation of insulating ferromagnetism are discussed.

Journal Article↗

PubMed2005

Intergranular giant magnetoresistance in a spontaneously phase separated perovskite oxide.

We present small-angle neutron scattering data proving that, on the insulating side of the metal-insulator transition, the doped perovskite cobaltite La(1-x)Sr(x)CoO(3) phase separates into ferromagnetic metallic clusters embedded in a nonferromagnetic matrix. This induces a hysteretic magnetoresistance, with temperature and field dependence characteristic of intergranular giant magnetoresistance (GMR). We argue that this system is a natural analog to the artificial structures fabricated by depositing nanoscale ferromagnetic particles in a metallic or insulating matrix; i.e., this material displays a GMR effect without the deliberate introduction of chemical interfaces.

Journal Article↗

PubMed2005

Position-sensing technologies for movement analysis in stroke rehabilitation.

Research has focused on improvement of the quality of life of stroke patients. Gait detection, kinematics and kinetics analysis, home-based rehabilitation and telerehabilitation are the areas where there has been increasing research interest. The paper reviews position-sensing technologies and their application for human movement tracking and stroke rehabilitation. The review suggests that it is feasible to build a home-based telerehabilitation system for sensing and tracking the motion of stroke patients.

Biomechanical Phenomena↗

PubMed2005

Melanin concentrating hormone innervation of caudal brainstem areas involved in gastrointestinal functions and energy balance.

Neural signaling by melanin-concentrating hormone and its receptor (SLC-1) has been implicated in the control of energy balance, but due to the wide distribution of melanin-concentrating hormone-containing fibers throughout the neuraxis, its critical sites of action for a particular effect have not been identified. The present study aimed to anatomically and functionally characterize melanin-concentrating hormone innervation of the rat caudal brainstem, as this brain area plays an important role in the neural control of ingestive behavior and autonomic outflow. Using retrograde tracing we demonstrate that a significant proportion (5-15%) of primarily perifornical and far-lateral hypothalamic melanin-concentrating hormone neurons projects to the dorsal vagal complex. In the caudal brainstem, melanin-concentrating hormone-ir axon profiles are distributed densely in most areas including the nucleus of the solitary tract, dorsal motor nucleus of the vagus, and sympathetic premotor areas in the ventral medulla. Close anatomical appositions can be demonstrated between melanin-concentrating hormone-ir axon profiles and tyrosine hydroxylase, GABA, GLP-1, NOS-expressing, and nucleus of the solitary tract neurons activated by gastric nutrient infusion. In medulla slice preparations, bath application of melanin-concentrating hormone inhibited in a concentration-dependent manner the amplitude of excitatory postsynaptic currents evoked by solitary tract stimulation via a pre-synaptic mechanism. Fourth ventricular administration of melanin-concentrating hormone (10 microg) in freely moving rats decreased core body temperature but did not change locomotor activity and food and water intake. We conclude that the rich hypothalamo-medullary melanin-concentrating hormone projections in the rat are mainly inhibitory to nucleus of the solitary tract neurons, but are not involved in the control of food intake. Projections to ventral medullary sites may play a role in the inhibitory effect of melanin-concentrating hormone on energy expenditure.

Animals↗

PubMed2005

Human cystic echinococcosis in two Mongolian communities in Hobukesar (China) and Bulgan (Mongolia).

In order to investigate the prevalence of human cystic echinococcosis (CE) in traditional Mongolian communities in western Mongolia and Xinjiang (northwest China), studies were carried out between 1995 and 2000, on two ethnically identical populations in Hobukesar (China) and Bulgan (Mongolia). The prevalence of human hepatic CE in the two communities was significantly different. In Hobukesar, human CE prevalence by ultrasound was 2.7% (49/1844), while in Bulgan it was 0.2% (4/1609) (P<0.001). Dog surveys showed that coproantigen-positive rates or dog necropsy positives were similar in both communities (35.0% in Hobukesar and 35.7% in Bulgan). Comparing possible risk factors, there appeared to be some significant differences between the two communities, which might contribute to the observed difference in CE prevalence. These included: the proportion of herdsman or farmers recorded; the proportions of dog ownership and livestock ownership; and the proportion of families practising home slaughter. The presence of a Russian dog-dosing programme up to the mid-1980s may explain the lower prevalence of human CE in the Bulgan population; no similar programme operated in the China-administered Hobukesar community.

Animals↗

PubMed2005

Electric field-induced magnetization switching in epitaxial columnar nanostructures.

We present direct evidence for room-temperature magnetization reversal induced by an electric field in epitaxial ferroelectric BiFeO3-ferrimagnetic CoFe2O4 columnar nanostructures. Piezoelectric force microscopy and magnetic force microscopy were used to locally image the coupled piezoelectric-magnetic switching. Quantitative analyses give a perpendicular magnetoelectric susceptibility of approximately 1.0 x 10(-2) G cm/V. The observed effect is due to the strong elastic coupling between the two ferric constituents as the result of the three-dimensional heteroepitaxy.

Journal Article↗

PubMed2005

Comparison of high-capacity and first-generation adenoviral vector gene delivery to murine muscle in utero.

In utero gene delivery could offer the advantage of treatment at an early stage for genetic disorders such as Duchenne muscular dystrophy (DMD) in which the inevitable process of muscle degeneration is already initiated at birth. Furthermore, treatment of fetal muscle with adenoviral (Ad) vectors is attractive because of a high density of Ad receptors, easy vector accessibility due to immaturity of the basal lamina and the possibility of treating stem cells. Previously, we demonstrated the efficient transduction of fetal muscle by high-capacity Ad (HC-Ad) vectors. In this study, we compared HC-Ad and first-generation Ad (FG-Ad) vectors for longevity of lacZ transgene expression, toxicity and induction of immunity after direct vector-mediated in utero gene delivery to fetal C57BL/6 mice muscle 16 days after conception (E-16). The total amount of beta-galactosidase (betagal) expressed from the HC-Ad vector remained stable for the 5 months of the study, although the concentration of betagal decreased due to muscle growth. Higher survival rates that reflect lower levels of toxicity were observed in those mice transduced with an HC-Ad vector as compared to an FG-Ad vector. The toxicity induced by FG-Ad vector gene delivery was dependent on mouse strain and vector dose. Animals treated with either HC-Ad and FG-Ad vectors developed non-neutralizing antibodies against Ad capsid and antibodies against betagal, but these antibodies did not cause loss of vector genomes from transduced muscle. In a mouse model of DMD, dystrophin gene transfer to muscle in utero using an HC-Ad vector restored the dystrophin-associated glycoproteins. Our results demonstrate that long-term transgene expression can be achieved by HC-Ad vector-mediated gene delivery to fetal muscle, although strategies of vector integration may need to be considered to accommodate muscle growth.

Adenoviridae↗