Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 37 records · Page 2Linked to original sources

PubMed2006

Towards hematopoietic stem cell-mediated protection against infection with human immunodeficiency virus.

The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful intervention. For long-term protection of both of these lineages, genetic modification of hematopoietic stem cells (HSCs) would be required. Here, we tested whether HSCs and their progeny can be modified to express therapeutic levels of M87o, a gammaretroviral vector encoding an artificial transmembrane molecule that blocks fusion-mediated uptake of HIV. In serial murine bone marrow transplantations, efficient and multilineage expression of M87o was observed for more than 1 year (range 37-75% of mononuclear cells), without signs of toxicity related to the transmembrane molecule. To allow enrichment of M87o-modified HSCs after transplant, we constructed vectors coexpressing the P140K mutant of O(6)-methylguanine-DNA-methyltransferase (MGMT-P140K). This clinically relevant selection marker mediates a survival advantage in HSCs if exposed to combinations of methylguanine-methyltransferase (MGMT) inhibitors and alkylating agents. A bicistronic vector mediated sufficient expression of both M87o and MGMT to confer a selective survival advantage in the presence of HIV and alkylating agents, respectively. These data encourage further investigations in large animal models and clinical trials.

AIDS Vaccines↗

PubMed2006

Detection of Hong Kong 97-like H5N1 influenza viruses from eggs of Vietnamese waterfowl.

Three H5N1 influenza viruses were isolated from shell washes of duck and goose eggs confiscated from travelers coming from Vietnam. All eight gene segments of these viruses share high sequence identity with the H5N1 avian influenza viruses that caused outbreaks in poultry and humans in Hong Kong in 1997. Animal studies indicate that these isolated viruses are able to replicate in mouse lung and could be found in the organs of ducks without causing any clinical signs or death. However, the viruses are highly pathogenic for chickens. Although the source of these recently isolated Hong Kong 97-like H5N1 viruses is undetermined, their detection in the egg shell of duck and goose suggests that this particular genotype of H5N1 virus may have re-emerged in nature or may have been circulating continuously.

Animals↗

PubMed2006

Dielectron widths of the Gamma(1S,2S,3S) resonances.

We determine the dielectron widths of the Gamma(1S), Gamma(2S), and Gamma(3S) resonances with better than 2% precision by integrating the cross section of e+e- -->Gamma over the e+e- center-of-mass energy. Using e+e- energy scans of the Gamma resonances at the Cornell Electron Storage Ring and measuring Gamma production with the CLEO detector, we find dielectron widths of 1.252+/-0.004(sigma(stat))+/-0.019(sigma(syst)) keV, 0.581+/-0.004+/-0.009 keV, and 0.413+/-0.004+/-0.006 keV for the Gamma(1S), Gamma(2S), and Gamma(3S), respectively.

Journal Article↗

PubMed2006

Measurement of sigma(e+e- -->psi(3770)-->hadrons) at Ec.m.=3773 MeV.

We measure the cross section for e+e- -->psi(3770) -->hadrons at Ec.m.=3773 MeV to be (6.38+/-0.08(+0.41)(-0.30) nb using the CLEO detector at the CESR e+e- collider. The difference between this and the e+e- -->psi(3770) -->DD cross section at the same energy is found to be (-0.01+/-0.08(+0.41)(-0.30) nb. With the observed total cross section, we extract Gamma(ee)(psi(3770))=(0.204+/-0.003(+0.041)(-0.027) keV. Uncertainties shown are statistical and systematic, respectively.

Journal Article↗

PubMed2006

Observation of psi(3770) --> pi pi J/psi and measurement of Gamma ee[psi(2S)].

We observe signals for the decays psi(3770) --> XJ/psi from data acquired with the CLEO detector operating at the CESR e+ e- collider with square root of s = 3773 MeV. We measure the following branching fractions Beta(psi(3770) --> XJ/psi and significances: (189 +/- 20 +/- 20) x 10(-5) (11.6sigma) for X = pi+ pi-, (80 +/- 25 +/- 16) x 10(-5) (3.4sigma) for X = pi0 pi0, and (87 +/- 33 +/- 22) x 10(-5) (3.5sigma) for X = eta, where the errors are statistical and systematic, respectively. The radiative return process e+ e- --> gamma psi(2S) populates the same event sample and is used to measure Gamma ee[psi(2S)] = (2.54 +/- 0.03 +/- 0.11) keV.

Journal Article↗

PubMed2006

New measurements of Cabibbo-suppressed decays of mesons with the CLEO-c detector.

Using of data collected with the CLEO-c detector, we report on first observations and measurements of Cabibbo-suppressed decays of D mesons in the following six decay modes: pi+ pi- pi0 pi0, pi+ pi+ pi- pi- pi0, pi+ pi0 pi0, pi+ pi+ pi- pi0, eta pi0, and omega pi+ pi-. Improved branching fraction measurements in eight other multipion decay modes are also presented. The measured D --> pi pi rates allow us to extract the ratio of isospin amplitudes A(DeltaI = (3/2) / A(DeltaI = (1/2)) = 0.420 +/- 0.014(stat) +/- 0.016(syst) and the strong phase shift of delta1 = (86.4 +/- 2.8 +/- 3.3) degrees, which is quite large and now more precisely determined.

Journal Article↗

PubMed2006

Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions.

BACKGROUND AND AIMS: In the liver, stellate cells play several important (patho)physiological roles. They express a broad but variable spectrum of intermediate filament (IF) proteins. The aim of this study was to investigate the expression and functions of the intermediate filament protein synemin in hepatic stellate cells (HSCs). METHODS: In isolated and cultured rat HSCs, synemin expression was examined by quantitative reverse transcriptase polymerase chain reaction, western blotting, and immunocytochemistry. Protein-protein interaction between synemin and possible binding partners was investigated by co-immunoprecipitation and confocal microscopy. RESULTS: Expression of synemin was significantly downregulated with increased culture time. In 1-day cultured HSCs, synemin associated with other IF proteins (GFAP, desmin, and vimentin), and with the focal adhesion proteins vinculin and talin, but not with alpha-actinin or paxillin. Synemin IF and focal adhesion proteins co-localised in long slender processes, but not in the lamellipodia. In human and rat liver tissue, the presence of synemin was investigated by immunohistochemistry. In normal rat and human livers, synemin immunoreactivity was found in HSCs, smooth muscle cells of hepatic arterioles, and nerve bundles in portal tracts, but not in portal fibroblasts. In CCl4-intoxicated rat livers and in human cirrhotic livers, immunoreactivity for synemin in the parenchymal tissue was decreased. Thus synemin was expressed in quiescent HSCs but not in portal fibroblasts; and synemin expression decreased with HSC activation in vivo during chronic liver damage and with HSC activation in culture. CONCLUSIONS: Synemin forms heteropolymeric filaments with type-III IF proteins and acts as a bridging protein between IFs and a specific type of focal adhesions.

Animals↗

PubMed2006

Increased vulnerability to nicotine self-administration and relapse in alcohol-naive offspring of rats selectively bred for high alcohol intake.

The prevalence of smoking in human alcoholics is substantially higher than in the general population, and results from twin studies suggest that a shared genetic vulnerability underlies alcohol and nicotine addiction. Here, we directly tested this hypothesis by examining nicotine-taking behavior in alcohol-naive offspring of alcohol-preferring (P) rats and alcohol-nonpreferring (NP) rats that had been selectively bred for high and low alcohol intake. The self-administration of intravenous nicotine (0.015-0.060 mg/kg per infusion) in P rats was more than twice than that of NP rats. Nicotine seeking induced by reexposure to nicotine cues in extinction tests was also substantially greater in P rats than in NP rats. In a subsequent relapse test, priming nicotine injections reinstated drug seeking in P rats but not NP rats. P rats also self-administered higher amounts of oral sucrose (1-20%) than NP rats, a finding consistent with previous reports. In contrast, self-administration of intravenous cocaine (0.1875-1.125 mg/kg per infusion) was remarkably similar in the P and NP rats; however, P-NP differences in cocaine seeking emerged in subsequent extinction and cocaine priming-induced reinstatement tests. In both cases, lever responding was higher in P rats than in NP rats. Thus, alcohol-naive offspring of rats genetically selected for high alcohol intake are highly susceptible to nicotine self-administration and relapse, and this susceptibility is not likely caused by general reward deficits in NP rats. The present findings provide experimental evidence for the hypothesis that a shared genetic determinant accounts for the co-abuse of nicotine and alcohol.

Alcoholism↗

PubMed2006

Effects of bee venom peptidergic components on rat pain-related behaviors and inflammation.

To identify the active components of honeybee venom in production of inflammation and pain-related behaviors, five major peptidergic subfractions were separated, purified and identified from the whole honeybee venom. Among them, four active peptidergic components were characterized as apamin, mast-cell degranulating peptide (MCDP), phospholipase A(2) (PLA(2))-related peptide and melittin, respectively. All five subfractions were effective in production of local inflammatory responses (paw edema) in rats although the efficacies were different. Among the five identified subfractions, only MCDP, PLA(2)-related peptide and melittin were able to produce ongoing pain-related behaviors shown as paw flinches, while only apamin and melittin were potent to produce both thermal and mechanical hypersensitivity. As shown in our previous report, melittin was the most potent polypeptide in production of local inflammation as well as ongoing pain and hypersensitivity. To further explore the peripheral mechanisms underlying melittin-induced nociception and hypersensitivity, a single dose of capsazepine, a blocker of thermal nociceptor transient receptor potential vanilloid receptor 1, was treated s.c. prior to or after melittin administration. The results showed that both pre- and post-treatment of capsazepine could significantly prevent and suppress the melittin-induced ongoing nociceptive responses and thermal hypersensitivity, but were without influencing mechanical hypersensitivity. The present results suggest that the naturally occurring peptidergic substances of the whole honeybee venom have various pharmacological potencies to produce local inflammation, nociception and pain hypersensitivity in mammals, and among the five identified reverse-phase high pressure liquid chromatography subfractions (four polypeptides), melittin, a polypeptide occupying over 50% of the whole honeybee venom, plays a central role in production of local inflammation, nociception and hyperalgesia or allodynia following the experimental honeybee's sting. Peripheral transient receptor potential vanilloid receptor 1 is likely to be involved in melittin-produced ongoing pain and heat hyperalgesia, but not mechanical hyperalgesia, in rats.

Amino Acid Sequence↗

PubMed2006

Transhemispheric functional reorganization of the motor cortex induced by the peripheral contralateral nerve transfer to the injured arm.

Peripheral nerve injury in a limb usually causes functional reorganization of the contralateral motor cortex. However, a dynamic process of the novel transhemispheric functional reorganization in the motor cortex was found in adult rats after transferring the seventh cervical nerve root from the contralateral healthy side to the injured limb. Initially the ipsilateral motor cortex activated the injured forepaw for 5 months after the operation. Then, both hemispheres of the cortex activated the injured forepaw, and finally the contralateral cortex exclusively controlled the injured forepaw. It is concluded an extensive functional shift occurred between two hemispheres based on neural plasticity in the CNS. The experimental results of the later lesions of the ipsilateral cortex suggest that maintaining transhemispheric functional reorganization does not depend on the corpus callosum, but depends on mechanisms involving central axonal sprouting. Possible mechanisms underlying the alternative changes in cortical functions were discussed in rats and in patients having similar operations.

Animals↗

PubMed2006

Estimation of photon dose generated by a short pulse high power laser.

The authors obtain a new equation to estimate the forward component of a photon dose generated through the interaction between a target and a short pulse high power laser. As the equation is quite simple, it is useful for calculating the photon dose. The equation shows that the photon dose is proportional to the electron temperature in the range>3 MeV and proportional to the square of the electron temperature in the range<3 MeV. The dose estimated with this method is roughly consistent with the result of Monte Carlo simulation. With some assumptions and corrections, it can reproduce experimental results obtained and the dose result calculated at other laboratories.

Electrons↗

PubMed2006

Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS.

The authors have previously shown that acute lung injury (ALI) produces a wide spectrum of pathological processes in patients who die of severe acute respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV) nucleoprotein is detectable in the lungs, and other organs and tissues, in these patients. In the present study, immunohistochemistry (IHC) and in situ hybridization (ISH) assays were used to analyse the expression of angiotensin-converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory cytokines (PICs) including MCP-1, TGF-beta1, TNF-alpha, IL-1beta, and IL-6 in autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its RNA were only detected in ACE2+ cells in the lungs and other organs, indicating that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2+ cells, but not in the uninfected cells. These results suggest that cells infected by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated damage to the lungs and other organs, resulting in ALI and, subsequently, multi-organ dysfunction. Therefore application of PIC antagonists may reduce the severity and mortality of SARS.

Acute Disease↗

PubMed2006

Phylogenetic analysis of porcine endogenous retroviruses expressed in Chinese pigs based on envelope sequences.

The promise of successful clinical xenotransplantation is now offset by the potential risk of transmission of porcine endogenous retrovirus (PERV). PERV consists of three subtypes according to the varieties of env sequences. We analyzed PERV subtypes in two species of Chinese pigs (Banna minipig inbred, BMI, and Wu-Zhi-Shan pig, WZSP). Positive A and B were detected while positive C was absent in the analyzed Chinese pigs. The polymerase chain reaction products were then cloned into a pGEM-T vector system and sequenced. Phylogenetic trees were constructed from the translated amino acids of PERVs and other type C and type D retrovirus, as well as the lentivirus in the GeneBank. The results suggested that PERV-A and PERV-B that exist in Chinese pig genomes share similarities with other PERV from the GeneBank and some type C retroviruses, including lymphotropic, leukemic and endogenous retroviruses.

Amino Acid Sequence↗

PubMed2006

In vivo screening of porcine endogenous retrovirus in Chinese Banna minipig inbred.

The risk of porcine endogenous retrovirus (PERV) infection is one of the major barriers in clinical trials of pig-to-human xenotransplantation. Previous experiments showed that PERV could infect many types of human and nonhuman primate cells, but there is no reported evidence of in vivo infection. In this study, extracted genomic DNA from tissues of seventeen pigs was analyzed using specific sequence primers for gag, pol, and env. The results suggested that PERV exist in the genomes of all tissues. A subtype analysis indicated that PERV-A and PERV-B were in the tissue genome with no positive PERV-C. A greater understanding of the properties of PERV in different pig tissues is necessary to evaluate the risk posed by PERV.

Animals↗

PubMed2006

The lack of inhibition of porcine endogenous retrovirus by small interference RNA designed from the long terminal regions.

Xenotransplantation from pigs may offer a potential solution to the organ shortage. However, there remains the risk of xenoinfection by porcine endogenous retroviruses (PERVs) that cannot be eliminated by breeding pigs under specified pathogen-free conditions. RNA interference is a new method to inhibit the expression of a specific gene. Here, we designed two siRNAs from the long terminal repeat of PERV. Our results showed that these siRNAs had no inhibitory effects. The possible reasons for this are an off-target effect or a problem with specific sequence of RNAi. Future work should focus on siRNAs from conserved regions of other PERV genes.

Animals↗

PubMed2006

Two-dimensional assembly and local redox-activity of molecular hybrid structures in an electrochemical environment.

The self-assembly and redox-properties of two viologen derivatives, N-hexyl-N'-(6-thiohexyl)-4,4'-bipyridinium bromide (HS-6V6-H) and N,N'-bis(6-thiohexyl)-4,4'-bipyridinium bromide (HS-6V6-SH), immobilized on Au(lll)-(1 x 1) macro-electrodes were investigated by cyclic voltammetry, surface enhanced infrared spectroscopy (SEIRAS) and in situ scanning tunneling microscopy (STM). Depending on the assembly conditions one could distinguish three different types of adlayers for both viologens: a low coverage disordered and an ordered "striped" phase of flat oriented molecules as well as a high coverage monolayer composed of tilted viologen moieties. Both molecules, HS-6V6-H and HS-6V6-SH, were successfully immobilized on Au(poly) nano-electrodes, which gave a well-defined redox-response in the lower pA-current range. An in situ STM configuration was employed to explore electron transport properties of single molecule junctions Au(T)/HS-6V6-SH(HS-6V6-H)/Au(S). The observed sigmoidal potential dependence, measured at variable substrate potential E(S) and at constant bias voltage (E(T) - E(S)), was attributed to electronic structure changes of the viologen moiety during the one-electron reduction/re-oxidation process V2+ < -- > V+*. Tunneling experiments in asymmetric, STM-based junctions Au(T)-S-6V6-H/Au(S) revealed current (i(T))-voltage (E(T)) curves with a maximum located at the equilibrium potential of the redox-process V2+ < -- > V+*. The experimental i(T)--E(T) characteristics of the HS-6V6-H-modified tunneling junction were tentatively attributed to a sequential two-step electron transfer mechanism.

Journal Article↗

PubMed2006

Living environment and schooling of children with HIV-infected parents in southwest China.

A cross-sectional household survey was conducted in Longchuan County, China, to study the lives of children with HIV-infected parents. Registered HIV-infected drug users and their households were approached and information about the living environment of children < or =15 years of age was collected. Of the 266 households interviewed, there were 213 children < or =15 years old. Forty percent of the children had lost at least one parent. Most of the children resided in a household with low economic status and a high dependency ratio. One-half of the children experienced discordant family relations, family anxiety and shame. Compared to orphans, non-orphans and their families were less likely to receive social support from the community. Orphans and older children were less likely to attend school and more likely to be truant if enrolled in school. Findings in the current study suggest that many children whose parents are infected with HIV or have died from HIV are living in stressful environments with minimal support from the community. Efforts should be taken to provide support and supervision to these children.

Absenteeism↗

PubMed2006

Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population.

Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF-alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty-three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case-control study in the Beijing area of China. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP-PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the -238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF-alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.

Adult↗