Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 37 records · Page 2Linked to original sources

PubMed2005

The triplet channel in the photodissociation of ozone in the Hartley band: classical trajectory surface hopping analysis.

The triplet channel in the photodissociation of ozone in the Hartley band, O3 + hv-->O(3P) + O2(3sigma), is investigated by means of a classical trajectory surface hopping method using ab initio diabatic potential energy surfaces for the B and the R states. Because of the strong recoil in the R state along the breaking O-O bond, O2(3sigma) is produced with a high rotational energy. The nonadiabatic transition probability depends markedly on the coordinate along the crossing seam. As a consequence a unique correlation is found between the internuclear geometry at the crossing and the final vibrational state of O2(3sigma). The calculated distribution of the translational energy is in good accord with the measured distribution.

Journal Article↗

PubMed2005

Cerebral folate deficiency with developmental delay, autism, and response to folinic acid.

The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the biologically active form of folates in CSF and blood. Folate and B12 levels were normal in peripheral tissues, suggesting cerebral folate deficiency. Treatment with folinic acid corrected CSF abnormalities and improved motor skills.

Adaptation, Physiological↗

PubMed2005

Experimental and theoretical investigation of the reaction NH(X3Sigma-) + H(2S)-->N(4S) + H2(X1)Sigmag +).

The rate coefficient of the reaction NH(X (3)Sigma(-)) + H((2)S)-->(k(1a) )N((4)S) + H(2)(X (1)Sigma(g) (+)) is determined in a quasistatic laser-flash photolysis, laser-induced fluorescence system at low pressures (2 mbar< or =p< or =10 mbar). The NH(X) radicals are produced via the quenching of NH(a(1)Delta) (obtained by photolyzing HN(3)) with Xe whereas the H atoms are generated in a H(2)He microwave discharge. The NH(X) concentration profile is measured under pseudo-first-order condition, i.e., in the presence of a large excess of H atoms. The room temperature rate coefficient is determined to be k(1a) = (1.9 +/- 0.5) x 10(12) cm(3) mol(-1) s(-1). It is found to be independent of the pressure in the range considered in the present experiment. A global potential energy surface for the (4)A(") state is calculated with the internally contracted multireference configuration interaction method and the augmented correlation consistent polarized valence quadruple zeta atomic basis. The title reaction is investigated by classical trajectory calculations on this surface. The theoretical room temperature rate coefficient is k(1a) = 0.92 x 10(12)cm(3) mol(-1) s(-1). Using the thermodynamical data for the atoms and molecules involved, the rate coefficient for the reverse reaction, k(-1a), is also calculated. At high temperatures it agrees well with the measured k(-1a).

Journal Article↗

PubMed2005

The Huggins band of ozone: assignment of hot bands.

The "hot bands" of the Huggins band of ozone are assigned, in both the 218 K and the 295 K spectrum. The assignment is based on intensities calculated with three-dimensional vibrational wave functions for the electronic ground state (X) and the excited state (B). The hot-band structures in the 218 K spectrum all can be assigned to transitions starting from vibrational states with one quantum of stretching excitation in the ground electronic state. The 295 K spectrum shows new structures, which are due to transitions originating from vibrational states in the X state with two quanta of excitation of the stretching modes--despite very small Boltzmann factors. All structures in the low-energy range of the 295 K spectrum, even the very weak ones, thus can be uniquely interpreted. The significance of hot bands results from the strong increase of Franck-Condon factors with excitation of the stretching modes in both the lower and/or the upper electronic states, whose equilibrium bond lengths differ significantly.

Journal Article↗

PubMed2005

A mechanistic basis for the role of cycle arrest in the genetic toxicology of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of meat, induces tumors of the prostate, colon, and mammary gland when fed to rats. PhIP is readily absorbed and efficiently metabolized to a genotoxic derivative by CYP1 enzymes. Although metabolism and mutational potential of PhIP have previously been well characterized, the intervening cellular and genomic responses to the chemical are not fully understood. We have examined the cellular response to PhIP exposure in human mammary epithelial MCF10A cells, which retain characteristics of normal breast epithelial cells. Because these cells fail to activate PhIP, they were cocultured with a human lymphoblastoid cell line MCL-5, which constitutively expresses CYP1A1, and have been transfected to express human CYPs1A2, 2A6, 3A4, and 2E1. The MCL-5 cells were irradiated (2,000 rads) prior to coculture, rendering them unable to replicate yet still retaining metabolic competency. MCF10A cells were treated (in the presence of MCL-5 cells) with PhIP (1-100 microM) and harvested at various time-points. Compared to DMSO control, treatment (24 or 48 h) with PhIP resulted in a significant dose-dependent fall in cell number. Cells treated for 48 h then cultured in the absence of PhIP (and MCL-5 cells) for a further 6 days showed a much greater dose-dependent reduction in cell number. Flow cytometric analysis indicated that PhIP treatment (48 h) resulted in a dose-dependent accumulation of cells in the G1 population. Western blotting revealed elevated expression of p53 and the cyclin dependent kinase inhibitor p21WAF1/CIP1 after PhIP treatment. Levels of MDM2, a negative regulator of p53, and the hypophosphorylated form of RB were also elevated, consistent with the triggering of G1 cell cycle checkpoint. These cell cycle effects are critical, as they enable cells to effect genome repair, accept mutation, or eliminate excessively damaged cells.

Carcinogens↗

PubMed2005

A mathematical model for assessing control strategies against West Nile virus.

Since its incursion into North America in 1999, West Nile virus (WNV) has spread rapidly across the continent resulting in numerous human infections and deaths. Owing to the absence of an effective diagnostic test and therapeutic treatment against WNV, public health officials have focussed on the use of preventive measures in an attempt to halt the spread of WNV in humans. The aim of this paper is to use mathematical modelling and analysis to assess two main anti-WNV preventive strategies, namely: mosquito reduction strategies and personal protection. We propose a single-season ordinary differential equation model for the transmission dynamics of WNV in a mosquito-bird-human community, with birds as reservoir hosts and culicine mosquitoes as vectors. The model exhibits two equilibria; namely the disease-free equilibrium and a unique endemic equilibrium. Stability analysis of the model shows that the disease-free equilibrium is globally asymptotically stable if a certain threshold quantity (R0), which depends solely on parameters associated with the mosquito-bird cycle, is less than unity. The public health implication of this is that WNV can be eradicated from the mosquito-bird cycle (and, consequently, from the human population) if the adopted mosquito reduction strategy (or strategies) can make R0<1. On the other hand, it is shown, using a novel and robust technique that is based on the theory of monotone dynamical systems coupled with a regular perturbation argument and a Liapunov function, that if R0>1, then the unique endemic equilibrium is globally stable for small WNV-induced avian mortality. Thus, in this case, WNV persists in the mosquito-bird population.

Algorithms↗

PubMed2005

Imidazoline receptors associated with noradrenergic terminals in the rostral ventrolateral medulla mediate the hypotensive responses of moxonidine but not clonidine.

We determined whether the cardiovascular actions of central anti-hypertensive agents clonidine and moxonidine are dependent on noradrenergic or serotonergic innervation of the rostral ventrolateral medulla (RVLM) in conscious rabbits. 6-Hydroxydopamine (6-OHDA) or 5,6-dihydroxytriptamine (5,6-DHT) was injected into the RVLM to deplete noradrenergic and serotonergic terminals respectively. One, 2 and 4 weeks later, responses to fourth ventricular (4V) clonidine (0.65 microg/kg) and moxonidine (0.44 microg/kg) were examined. Destruction of noradrenergic pathways in the RVLM by 6-OHDA reduced the hypotensive response to 4V moxonidine to 62%, 47% and 60% of that observed in vehicle treated rabbits at weeks 1, 2 and 4 respectively. The moxonidine induced bradycardia was similarly attenuated (to 46% of vehicle). Conversely, 6-OHDA had no effect on the hypotensive or bradycardic effects of 4V clonidine. Efaroxan (I(1)-imidazoline receptor/alpha(2)-adrenoceptor antagonist; 3.5, 11, 35 microg/kg) and 2-methoxyidazoxan (alpha(2)-adrenoceptor antagonist; 0.3, 0.9, 3 microg/kg) equally reversed the hypotension to 4V clonidine, suggesting a mainly alpha(2)-adrenoceptor mechanism. Efaroxan preferentially reversed responses to moxonidine in both vehicle and 5,6-DHT groups and in the 1st week after 6-OHDA, suggesting a mechanism involving mainly I(1)-imidazoline receptors. This selectivity was subsequently lost in the 2nd and 4th weeks when the remaining hypotension was mainly mediated by alpha(2)-adrenoceptors. Depletion of serotonergic terminals did not alter the responses to either agonist nor did it change the relative effectiveness of the antagonists. Western blots of RVLM tissues probed with imidazoline and alpha(2)-adrenoceptor antisera showed a pattern of bands close to that reported in other species. The main effect of 6-OHDA was an 18% lower level of the 42 kDa imidazoline protein (P<0.05). We conclude that the hypotensive and bradycardic actions of moxonidine but not clonidine are mediated through imidazoline receptors and are dependent on intact noradrenergic pathways within the RVLM. Furthermore, the noradrenergic innervation may be associated with a 42 kDa imidazoline receptor protein.

5,6-Dihydroxytryptamine↗

PubMed2005

Genetic tests of biologic systems in affective disorders.

To liberate candidate gene analyses from criticisms of inexhaustiveness of examination of specific candidate genes, or incompleteness in the choice of candidate genes to study for specific neurobiological pathways, study of sizeable sets of genes pertinent to each putative pathophysiological pathway is required. For many years, genes have been tested in a 'one by one' manner for association with major affective disorders, primarily bipolar illness. However, it is conceivable that not individual genes but abnormalities in several genes within a system or in several neuronal, neural, or hormonal systems are implicated in the functional hypotheses for etiology of affective disorders. Compilation of candidate genes for entire pathways is a challenge, but can reasonably be carried out for the major affective disorders as discussed here. We present here five groupings of genes implicated by neuropharmacological and other evidence, which suggest 252 candidate genes worth examining. Inexhaustiveness of gene interrogation would apply to many studies in which only one polymorphism per gene is analyzed. In contrast to whole-genome association studies, a study of a limited number of candidate genes can readily exploit information on genomic sequence variations obtained from databases and/or resequencing, and has an advantage of not having the complication of an extremely stringent statistical criterion for association.

Bipolar Disorder↗

PubMed2005

Differential expression of prostaglandin E receptor subtype EP2 in rat uterus during early pregnancy.

PGE2 is essential for mammalian female reproduction. This study was to examine the expression of EP2 gene in the rat uterus during early pregnancy, delayed implantation and artificial decidualization by in situ hybridization and immunohistochemistry. There was no detectable EP2 mRNA expression in the uterus from days 1 to 4 of pregnancy (day 1 = day of vaginal sperm). A low level of EP2 immunostaining was observed in the luminal and glandular epithelium from days 1 to 4 of pregnancy. Both EP2 mRNA and protein expression were highly detected in the luminal epithelium at implantation sites on day 6 of pregnancy. EP2 expression decreased from day 7 of pregnancy and was undetectable on days 8 and 9 of pregnancy. After delayed implantation was terminated by estrogen treatment and the embryo implanted, both EP2 mRNA and protein expression were strongly observed in the luminal epithelium at the implantation site. There was no detectable EP2 expression in both control and decidualized uteri. In conclusion, these data suggest that EP2 expression at implantation site may play an important role during embryo implantation in rats.

Animals↗

PubMed2005

Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells.

Aim of the study was to explore the influence of hypoxia on multidrug resistance related genes and the potential role of hypoxia-inducible factor-1-alpha (HIF-1alpha) in formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. HepG2 cells were subjected to hypoxia in a cohort of exposed time. A cell model stably expressing HIF-1alpha was established by liposome-mediated transfection of plasmid pcDNA3/HIF-1alpha into HepG2 cells. Apoptosis of HepG2 cells exposed to hypoxia or transfected by plasmid pcDNA3/HIF-1alpha was detected by Flow Cytometry after administration of chemotherapeutic drug (5-Fu). Real-time fluorescent quantitative PCR and Western-blot technique were used to analyze the expressions of multidrug resistance related genes mdr1, MRP1 and LRP at mRNA and protein level, respectively. Apoptosis Index of HepG2 cells exposed to hypoxia stepped down as exposed time extended after administration of 5-Fu. The expression of mdr1, MRP1 and LRP gene and protein revealed a hypoxic time-dependent induction and was synchronous with the alterations of HIF-1alpha in HepG2 cells exposed to hypoxia. The expressions of these multidrug resistance related genes were remarkably increased in HIF-1alpha transfected HepG2 cells as compared to empty vector transfected cells. Apoptosis index of HIF-1alpha transfected cells was obviously less than that of control cells when they were simultaneously exposed to 5-Fu for 24hrs. In conclusion, ambient hypoxia might be one of the causes for the formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. Hypoxia-elicited multidrug resistance related protein expression might be a pathway for resistance of HepG2 cells to chemotherapeutics and HIF-1alpha might be involved in this process.

Apoptosis↗

PubMed2004

Correlated strength in the nuclear spectral function.

We have carried out an (e,e'p) experiment at high momentum transfer and in parallel kinematics to measure the strength of the nuclear spectral function S(k,E) at high nucleon momenta k and large removal energies E. This strength is related to the presence of short-range and tensor correlations, and was known hitherto only indirectly and with considerable uncertainty from the lack of strength in the independent-particle region. This experiment locates by direct measurement the correlated strength predicted by theory.

Journal Article↗

PubMed2004

Genetic inheritance of gene expression in human cell lines.

Combining genetic inheritance information, for both molecular profiles and complex traits, is a promising strategy not only for detecting quantitative trait loci (QTLs) for complex traits but for understanding which genes, pathways, and biological processes are also under the influence of a given QTL. As a primary step in determining the feasibility of such an approach in humans, we present the largest survey to date, to our knowledge, of the heritability of gene-expression traits in segregating human populations. In particular, we measured expression for 23,499 genes in lymphoblastoid cell lines for members of 15 Centre d'Etude du Polymorphisme Humain (CEPH) families. Of the total set of genes, 2,340 were found to be expressed, of which 31% had significant heritability when a false-discovery rate of 0.05 was used. QTLs were detected for 33 genes on the basis of at least one P value <.000005. Of these, 13 genes possessed a QTL within 5 Mb of their physical location. Hierarchical clustering was performed on the basis of both Pearson correlation of gene expression and genetic correlation. Both reflected biologically relevant activity taking place in the lymphoblastoid cell lines, with greater coherency represented in Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathways than in Gene Ontology database pathways. However, more pathway coherence was observed in KEGG pathways when clustering was based on genetic correlation than when clustering was based on Pearson correlation. As more expression data in segregating populations are generated, viewing clusters or networks based on genetic correlation measures and shared QTLs will offer potentially novel insights into the relationship among genes that may underlie complex traits.

Cell Line↗

PubMed2004

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

PubMed2004

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains.

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca2+ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca2+ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721deltaC and T7721deltaN cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721deltaC cells, but not affected in T7721deltaN cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca2+ mobilization although each domain may play different roles.

Antigens, CD↗

PubMed2004

Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex.

Caspase-11 is a key regulator of proinflammatory cytokine IL-1beta maturation and pathological apoptosis. Caspase-11 is not expressed in most tissues under normal condition, but highly inducible upon pathological stimulation such as in the presence of lipopolysaccharide (LPS). Here, we describe the identification and characterization of wedelolactone, a natural compound that inhibits LPS-induced caspase-11 expression in cultured cells by inhibiting NF-kappaB-mediated transcription. We demonstrate that wedelolactone is an inhibitor of IKK, a kinase critical for activation of NF-kappaB by mediating phosphorylation and degradation of IkappaBalpha.

Animals↗

PubMed2004

Searching for an enhanced predictive tool for mutagenicity.

The Multiple Computer Automated Structure Evaluation (MCASE) program was used to evaluate the mutagenic potential of organic compounds. The experimental Ames test mutagenic activities for 2513 chemicals were collected from various literature sources. All chemicals have experimental results in one or more Salmonella tester strains. A general mutagenicity data set and fifteen individual Salmonella test strain data sets were compiled. Analysis of the learning sets by the MCASE program resulted in the derivation of good correlations between chemical structure and mutagenic activity. Significant improvement was obtained as more data was added to the learning databases when compared with the results of our previous reports. Several biophores were identified as being responsible for the mutagenic activity of the majority of active chemicals in each individual mutagenicity module. It was shown that the multiple-database mutagenicity model showed a clear advantage over normally used single-database models. The expertise produced by this analysis can be used to predict the mutagenic potential of new compounds.

Databases, Factual↗

PubMed2004

Influence of tissue origins and external microenvironment on porcine foetal fibroblast growth, proliferative life span and genome stability.

One of the challenges of manipulating genes in primary cells is that the cells have a finite proliferation capacity. This, combined with the lower gene targeting efficiency of somatic cells, makes identification of targeted clones very difficult. The objective of this study was to establish a system that allows porcine foetal fibroblasts to reach their maximal proliferation capacity in vitro. The influence of fibroblast origin, stage of foetal development, cell seeding densities and concentration of foetal bovine serum (FBS) on the population doublings, the percentage of beta-galactosidase-activity-positive cells and the genome stability of foetal fibroblasts during in vitro culture was investigated. It was found that porcine foetal fibroblasts could be cultured for over 80 population doublings in the appropriate culture system. Fibroblasts from earlier stages of foetal development were better candidate cells than those from the later stages. Cells from the heart were more actively proliferative and more resistant to replicative senescence than those from the liver. Compared to 10% FBS content, 15% FBS provided better homeostatic support, not only to proliferative performance, but also in maintaining a normal karyotype. In addition, the proliferative life span of porcine foetal fibroblasts is also dependent on seeding density of the culture.

Animals↗

PubMed2004

Gastric distension alters frequency and regularity but not amplitude of the gastric slow wave.

Abstract The aim of this study was to assess effects of gastric distension on gastric slow waves using internal and cutaneous electrodes and the correlation between these two measurements. The study was performed in five dogs implanted with one pair of serosal electrodes and a gastric cannula. Gastric slow waves were recorded using both cutaneous and internal electrodes in several sessions with different volumes (150-600 mL) of gastric distension with a barostat balloon. Bethanechol was injected in one of sessions. The results revealed that (i) Gastric distension reduced slow wave frequency in a volume-dependent manner and induced bradyarrhythmia at a volume of 600 mL, but had no effects on the amplitude of gastric slow waves. (ii) The cutaneous electrogastrogram (EGG) was significantly correlated with the internal recording in slow wave frequency (r = 0.88, P < 0.001) and regularity (r = 0.44, P = 0.035). (iii) The EGG amplitude was not increased when the stomach was distended but increased after bethanechol. Gastric distension volume dependently reduces slow wave frequency and induces gastric dysrhythmia at a large volume. The frequency and rhythmicity of the slow wave measured from the EGG are significantly correlated with those recorded from the internal electrodes. Relative increase in EGG amplitude reflects contractility rather than the distension of the stomach.

Animals↗