Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 19 recordsLinked to original sources

PubMed2006

Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues.

The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA.

Acetylcholine↗

PubMed2006

Decreased levels of apolipoprotein A-I in plasma of schizophrenic patients.

This study aims to identify the effects of antipsychotics on plasma proteins, and on the proteins associated with schizophrenia. We applied proteomics technology to screen protein aberrations in Sprague-Dawley rats treated with antipsychotics and schizophrenic patients undergoing medication. ApoA-I was found significantly increased in the chlorpromazine-treated rats and decreased in the patients with treatment-resistant schizophrenia, which suggest that decreased levels of apoA-I might be associated with the pathology of schizophrenia and that chlorpromazine increases apoA-I levels as part of its therapeutic action.

Adult↗

PubMed2006

Mechanisms of action of the carcinogenic heterocyclic amine PhIP.

Formed during the cooking of meat, the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhIP) is mutagenic and carcinogenic. Although the metabolism and mutational effects of PhIP are well defined, the early cellular and genomic events by which it can induce neoplastic transformation are not yet fully characterised. These early cellular responses to genotoxic doses of PhIP were examined in a human mammary epithelial cell, MCF10A. Using Western blotting, PhIP was shown to induce expression of the DNA damage response proteins p53 and p21(WAF1/CIP1), and to inhibit cell growth while activating G1 cell cycle checkpoint, a consequence of PhIP-induced DNA damage. Using low doses of PhIP (previously shown to activate oestrogenic signalling), PhIP increased proliferation in the oestrogen receptor (ER)-negative MCF10A cell line and to activate the mitogen-activated protein kinase (MAPK) pathway. Inhibition of this pathway significantly reduced the PhIP-induced cell growth of MCF10A cells. The work presented here suggests that, further to its genotoxic properties, at levels close to human exposure PhIP stimulates cellular signalling pathways that are linked to the promotion and progression of neoplastic disease. It is possible that a combination of these DNA damaging and growth promoting properties provide a mechanism for the tumourigenicity of PhIP, and may be key determinants for the tissue specificity of PhIP-induced carcinogenesis.

Carcinogens↗

PubMed2006

Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines.

BACKGROUND: The restricted expression of ADAMTS-5 (A Disintegrin And Metalloproteinase with ThromboSpondin repeats-5) to the maternal-fetal interface in mice has led to this novel metalloproteinase being assigned the trivial name 'implantin'. METHODS: As a first step in determining whether ADAMTS-5 also contributes to the implantation process in humans, we have examined the spatiotemporal expression of this ADAMTS subtype in the endometrium during the menstrual cycle and pregnancy by immunohistochemical analysis. A quantitative competitive PCR (QC-PCR) strategy and western blotting were subsequently used to determine whether interleukin (IL)-1beta and transforming growth factor (TGF)-beta1, two cytokines involved in the formation of the maternal-fetal interface, were capable of regulating ADAMTS-5 messenger RNA (mRNA) and protein levels in primary cultures of stromal cells isolated from first trimester decidual tissues. RESULTS: ADAMTS-5 expression in the stroma of the human endometrium correlates with decidualization of this cellular compartment in vivo. IL-1beta was found to increase (P < 0.05) whereas TGF-beta1 decreased (P < 0.05) ADAMTS-5 mRNA and protein levels in decidual stromal cell cultures in a concentration- and time-dependent manner. These regulatory effects were attenuated by function-perturbing antibodies directed against either cytokine. CONCLUSIONS: ADAMTS-5 expression is restricted to decidualized stromal cells of the human endometrium in vivo and is subject to regulation by cytokines in vitro.

ADAM Proteins↗

PubMed2006

Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene.

In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested Hp alpha1/Hp alpha2 (Hp 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia is accompanied by both an altered expression of Hp protein and a different genotype distribution of Hp gene, demonstrating that Hp is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs.

Acute-Phase Proteins↗

PubMed2006

Spin-orbit mechanism of predissociation in the Wulf band of ozone.

Previously calculated resonance widths of the ground vibrational levels in the electronic states 1 (3)A" ((3)A(2)) and 1 (3)A' ((3)B(2)), which belong to the Wulf band system of ozone, are significantly smaller than observed experimentally. We demonstrate that predissociation is drastically enhanced by spin-orbit coupling between 1 (3)A"/X (1)A' and 1 (3)A'/1 (3)A". Multistate quantum mechanical calculations using ab initio spin-orbit coupling matrix elements give linewidths of optically bright components of the right order of magnitude.

Journal Article↗

PubMed2006

Absorption spectrum and assignment of the Chappuis band of ozone.

New global diabatic potential energy surfaces of the electronic states 1B1 and 1A2 of ozone and the non-adiabatic coupling surface between them are constructed from electronic structure calculations. These surfaces are used to study the visible photodissociation in the Chappuis band by means of quantum mechanical calculations. The calculated absorption spectrum and its absolute intensity are in good agreement with the experimental results. A vibrational assignment of the diffuse structures in the Chappuis band system is proposed on the basis of the nodal structures of the underlying resonance states.

Journal Article↗

PubMed2006

DLK1: increased expression in gliomas and associated with oncogenic activities.

DLK1 (delta-like) is a transmembrane and secreted protein in the epidermal growth factor-like homeotic family. Although expressed widely during embryonic development, only a few tissues retain the expression in adults. Neuroendocrine tumors often highly express this protein; therefore, we hypothesized that brain tumors might also express it. This study found that the expression of DLK1 in gliomas was higher than that in normal brain (P < 0.05). After stable transfection of a DLK1 cDNA expression vector into GBM cell lines, their proliferation was increased. Furthermore, they lost contact inhibition, had enhanced anchorage-independent growth in soft agar, and had significantly greater capacity to migrate. Western blot studies showed that expression of cyclin D1, CDK2, and E2F4 were increased, and Rb levels were decreased in these cells. DLK1 was found on the cell surface and secreted in the medium from the transfected GBM cells. DLK1-enriched condition medium stimulated the growth of glioblastoma multiforme cell lines and explants. DLK1 antibody blocked cell growth stimulated by DLK1. In summary, these results suggest that DLK1 may play a role in the formation or progression of gliomas.

Blotting, Western↗

PubMed2006

Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.

The mechanisms involved in the pathogenesis of ovarian cancer are poorly understood, but evidence suggests that aberrant activation of Wnt/beta-catenin signalling pathway plays a significant role in this malignancy. However, the molecular defects that contribute to the activation of this pathway have not been elucidated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a candidate for the regulation of cytoplasmic beta-catenin. In this study, we developed in situ hybridisation probes to evaluate the presence of FRAT1 and used an anti-beta-catenin antibody to evaluate by immunohistochemistry the expression levels and subcellular localisation of beta-catenin in ovarian cancer tissue microarrays. Expression of FRAT1 was found in some human normal tissues and 47% of ovarian adenocarcinomas. A total of 46% of ovarian serous adenocarcinomas were positive for FRAT1 expression. Accumulation of beta-catenin in the nucleus and/or cytoplasm was observed in 55% ovarian adenocarcinomas and in 59% of serous adenocarcinomas. A significant association was observed in ovarian serous adenocarcinomas between FRAT1 and beta-catenin expression (P<0.01). These findings support that Wnt/beta-catenin signalling may be aberrantly activated through FRAT1 overexpression in ovarian serous adenocarcinomas. The mechanism behind the overexpression of FRAT1 in ovarian serous adenocarcinomas and its significance is yet to be investigated.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and oncolytic adenovirotherapy have been investigated extensively in xenografic human tumor models established in immunocompromised nude mice. However, the effects of these therapies on syngeneic murine tumors in immunocompetent settings were not well documented. We hypothesized that TRAIL gene therapy used with an oncolytic adenovirus would overcome the weaknesses of the two therapies used individually. In this study, we evaluated the antitumor effects of an oncolytic adenovirus, Delta24, in both human and murine breast cancer cell lines. We also analyzed the effects of TRAIL gene therapy combined with oncolytic virotherapy in these cancer cells. Our results showed that Delta24 can replicate and help the E1-deleted adenovector replicate in murine cancer cells. We also found that these two therapies combined had greater antitumor activity than either one alone in both human and murine breast cancer cells lines and in the syngeneic breast cancer models established in immunocompetent mice. Moreover, Delta24 virotherapy alone and combined with TRAIL gene therapy dramatically reduced the spontaneous liver metastasis that originated in the subcutaneous 4T1 tumor established in Balb/c mice. These findings provide important considerations in the development and preclinical assessments of oncolytic virotherapy.

Adenoviridae↗

PubMed2006

Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes.

Heart failure results from the cumulative death of cardiomyocytes, and the inability of remaining cells to regenerate. Efforts toward transcriptional reprogramming of cardiomyocytes by overexpressing E1A or E2F1 have been limited by the inability of cardiomyocytes to enter and complete mitosis. Human CDC5 (hCDC5), a component of the pre-mRNA splicing complex, has been shown to regulate G2/M transit in asynchronously dividing cells. We now show that co-infection of recombinant adenoviruses expressing E1A/E1B and hCDC5 promotes cell cycle re-entry and G2/M progression in post-mitotic cardiomyocytes. Co-expression of E1A/E1B and hCDC5 induced nuclear localization of cyclin-dependent kinase 1 and cyclin B1, and was sufficient to promote mitotic entry as determined by an increase in mitotic index only in co-infected cells. E1A/E1B and hCDC5 promoted cell division, as evidenced by an increase in the number of cardiomyocytes following co-infection. Thus, overexpression of E1A/E1B and hCDC5 resulted in cell cycle re-entry, DNA synthesis, cell division, and an increase in cardiomyocyte number, suggesting the formation of new cardiomyocytes. These studies suggest that G1/S-phase transcriptional regulators, in combination with pre-mRNA splicing factors, such as CDC5, that regulate rate-limiting G2/M target genes may prove useful in developing therapies to stimulate myocardial regeneration.

Adenoviridae↗

PubMed2006

Bacterial killing in gastric juice--effect of pH and pepsin on Escherichia coli and Helicobacter pylori.

The susceptibility of Escherichia coli and Helicobacter pylori to pH and the effect of pepsin-mediated proteolysis were investigated. This was to establish the relative importance of their bacterial killing properties in gastric juice. Solutions in the pH range 1.5-7.4 with or without pig pepsin A were used, together with seven gastric juice samples obtained from patients undergoing routine gastric collection. Escherichia coli C690 (a capsulate strain), E. coli K-12 (a rough mutant) and Helicobacter pylori E5 were selected as the test organisms. Suspensions of bacteria (1x10(6) E. coli ml-1 and 1x10(8) H. pylori ml-1) were pre-incubated with test solutions at 37 degrees C for up to 2 h, and then cultured to establish the effect on subsequent growth. Survival of bacteria was diminished at pHs of less than 3.5, whereas killing required a pH of less than 2.5. Pre-incubation with pig pepsin at 0.5, 1.0 and 2.0 mg ml-1 at pH 3.5 reduced viable counts by 100% for E. coli 690 and E. coli K-12 after 100 min incubation. With H. pylori, the viable counts decreased to 50% of the control after 20 min incubation in 1 mg pepsin ml-1 at pH 2.5, 3.0 and 3.5. The gastric juices showed bactericidal activity at pH 3.5, and the rate of killing was juice dependent, with complete death of E. coli 690 occurring between 5 and 40 min post-incubation. Thus, killing of E. coli and H. pylori occurs optimally at pHs of less than 2.5. At pH 3.5, little effect is observed, whereas addition of pepsin alone or in gastric juice causes a marked increase in bacterial susceptibility, suggesting an important role for proteolysis in the killing of bacteria.

Colony Count, Microbial↗

PubMed2006

Development of gastric slow waves and effects of feeding in pre-term and full-term infants.

The aims of this study were to investigate the difference in developmental process of gastric slow waves and the effects of feeding in pre-term and full-term infants. Twenty-six pre-term and 31 full-term infants were enrolled in the study. Gastric myoelectrical activity was recorded using electrogastrography (EGG) from birth to month 6. An increase in the % of 2-4 cpm slow waves was noted in both pre-term (P < 0.01) and full-term infants (P < 0.04) from birth to month 4. The pre-term infants showed a reduced dominant EGG power at certain points of the study. (3) Breast or formula feeding resulted in no difference in the EGG in the full-term infants and showed a difference in the postprandial dominant power of the EGG in the pre-term infants only at month 2 after birth (P < 0.05) but not at other times. The gastric slow wave in pre-term infants is of a significantly reduced amplitude but similar rhythmicity. The method of feeding has no effects on the EGG in full-term infants and minimal effects (may be of non-clinical significance) on the EGG in pre-term infants as the difference was noted only at one time point during the 6-month follow-up study.

Bottle Feeding↗

PubMed2006

Is magnesium neuroprotective following global and focal cerebral ischaemia? A review of published studies.

Neuroprotective activity with magnesium associated with animal models of cerebral ischaemia, seizure, perinatal hypoxia/ischaemia, subarachnoid haemorrhage and traumatic brain injury has provided the justification for clinical stroke trials. However, the recent IMAGES stroke clinical trial found magnesium to be largely ineffective. Hence, due to the negative stroke trial outcome, current FAST-MAG trial and our own experience with magnesium in cerebral ischaemia animal models, we thought it prudent to review these preclinical and clinical studies. We reviewed nine studies describing the use of magnesium following global cerebral ischaemia and fourteen following focal cerebral ischaemia. Four global ischaemia and six focal ischaemia studies did not show a significant neuroprotective effect with magnesium. In the majority of positive magnesium studies animal body temperature was not monitored post-ischaemia. Thus the effects of post-ischaemic hypothermia cannot be ruled out as a confounding factor in positive magnesium cerebral ischaemia studies. Moreover, data from our own laboratory indicates that magnesium is only neuroprotective when combined with post-ischaemic hypothermia. These data provide a possible explanation of why the IMAGES trial was largely unsuccessful, as current stroke patient management does not involve hypothermia induction. Future preclinical and clinical cerebral ischaemia trials with magnesium should consider combining treatment with mild hypothermia.

Animals↗

PubMed2005

Infrared spectrum of cyclic ozone: a theoretical investigation.

The infrared absorption spectrum of cyclic ozone is calculated by means of a new ab initio potential energy surface, the dipole moment function, and exact quantum mechanical dynamics calculations. Five different isotopomers are considered. The absorption line for excitation of the bending fundamental near 800 cm(-1) is by far the strongest band; all other bands are more than one order of magnitude less intense. This spectral pattern as well as the isotope shifts for the various isotopomers are important for identifying cyclic ozone. Several possibilities for accessing the ring minimum of cyclic ozone are also discussed on the basis of recent electronic structure calculations.

Journal Article↗

PubMed2005

The photodissociation of ozone in the Hartley band: a theoretical analysis.

Three-dimensional diabatic potential energy surfaces for the lowest four electronic states of ozone with 1A' symmetry-termed X, A, B, and R-are constructed from electronic structure calculations. The diabatization is performed by reassigning corresponding energy points. Although approximate, these diabatic potential energy surfaces allow one to study the uv photodissociation of ozone on a level of theory not possible before. In the present work photoexcitation in the Hartley band and subsequent dissociation into the singlet channel, O3X+hnu-->O(1D)+O2(a 1Deltag), are investigated by means of quantum mechanical and classical trajectory calculations using the diabatic potential energy surface of the B state. The calculated low-resolution absorption spectrum as well as the vibrational and rotational state distributions of O2(a 1Deltag) are in good agreement with available experimental results.

Chemistry, Physical↗

PubMed2005

Spectrally narrowed external-cavity high-power stack of laser diode arrays.

We describe an effective external cavity for narrowing the spectral linewidth of a multiarray stack of laser diode arrays. For a commercially available 279-W free-running five-array laser diode array operating at 60 A, we narrow the spectral linewidth to 0.40 nm at FWHM with 115 W of cw power output. This technique leads to the possibility of higher-efficiency, lower-cost production of hyperpolarized noble gases for magnetic resonance imaging.

Journal Article↗

PubMed2005

Experimental and theoretical investigations of the reactions NH(X 3Sigma-) + D(2S)-->ND(X 3Sigma-) + H(2S) and NH(X 3Sigma-) + D(2S)-->N(4S) + HD(X 1Sigmag+).

The rate coefficient of the reaction NH(X (3)Sigma(-))+D((2)S)-->(k(1) )products (1) is determined in a quasistatic laser-flash photolysis, laser-induced fluorescence system at low pressures. The NH(X) radicals are produced by quenching of NH(a (1)Delta) (obtained in the photolysis of HN(3)) with Xe and the D atoms are generated in a D(2)/He microwave discharge. The NH(X) concentration profile is measured in the presence of a large excess of D atoms. The room-temperature rate coefficient is determined to be k(1)=(3.9+/-1.5) x 10(13) cm(3) mol(-1) s(-1). The rate coefficient k(1) is the sum of the two rate coefficients, k(1a) and k(1b), which correspond to the reactions NH(X (3)Sigma(-))+D((2)S)-->(k(1a) )ND(X (3)Sigma(-))+H((2)S) (1a) and NH(X (3)Sigma(-))+D((2)S)-->(k(1b) )N((4)S)+HD(X (1)Sigma(g) (+)) (1b), respectively. The first reaction proceeds via the (2)A(") ground state of NH(2) whereas the second one proceeds in the (4)A(") state. A global potential energy surface is constructed for the (2)A(") state using the internally contracted multireference configuration interaction method and the augmented correlation consistent polarized valence quadrupte zeta atomic basis. This potential energy surface is used in classical trajectory calculations to determine k(1a). Similar trajectory calculations are performed for reaction (1b) employing a previously calculated potential for the (4)A(") state. The calculated room-temperature rate coefficient is k(1)=4.1 x 10(13) cm(3) mol(-1) s(-1) with k(1a)=4.0 x 10(13) cm(3) mol(-1) s(-1) and k(1b)=9.1 x 10(11) cm(3) mol(-1) s(-1). The theoretically determined k(1) shows a very weak positive temperature dependence in the range 250< or =TK< or =1000. Despite the deep potential well, the exchange reaction on the (2)A(") ground-state potential energy surface is not statistical.

Journal Article↗