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Biomedical subjects

Z Liu

Publications and source records attributed to Z Liu.

At least 145 records · Page 8Linked to original sources

Reductive dehalogenation of gas-phase chlorinated solvents using a modified fuel cell.

The reductive dehalogenation of gas-phase chlorinated alkanes (CCl4, CHCl3, and 1,1,1-trichloroethane) and alkenes (perchloroethene (PCE) and trichloroethene (TCE)) was conducted in a modified fuel cell. The fuel-cell performance was a function of cathode material, electric potential, temperature, target compound identity and gas-phase concentration, partial pressure of O2 in the cathode chamber, and cathode condition (time in service). TCE conversion was approximately first order in TCE concentration with half-lives of fractions of a second. Under the same reactor conditions, CCl4 transformation was faster than CHCl3, and TCE reduction was faster than PCE. Rates of both CCl4 and PCE transformation increased substantially with temperature in the range of 30-70 degrees C. At 70 degrees C and a potential (potential of the cathode minus that of the anode) of -0.4 V, single-pass CCl4 conversions were approximately 90%. Mean residence time for gases in the porous cathode was much less than 1 s. The presence of even 5% O2(g) in the influent to the cathode chamber had a deleterious effect on reactor performance. Performance also deteriorated with time in service, perhaps due to the accumulation of HCl on the cathode surface. Conversion efficiency was restored, however, by temporarily eliminating the halogenated target(s) from the influent stream or by briefly reversing fuel-cell polarity.

Air Pollutants↗

A novel mechanism of dopamine neurotoxicity involving the peripheral extracellular and the plasma membrane dopamine transporter.

Chinese hamster ovary cells stably expressing a rat dopamine transporter (designated D8 cells) and neuroblastoma SK-N-SH cells were used as two model systems to study dopamine neurotoxicity. Within 24 h, 1-10 mM dopamine induced D8 cells into apoptosis while 20-200 microM dopamine induced SK-N-SH cells into cell death. The viability of both cell types decreased in a dose-dependent manner. However, the dopamine uptake activity of D8 cells at 10 mM was not significantly higher than the uptake at 100 microM, suggesting that it was not the high concentration of intracellular dopamine that induced D8 cells into apoptosis, but rather dopamine found in the extracellular space. Furthermore, cocaine, an inhibitor of dopamine uptake, could not block cell death induced by dopamine. Forskolin, an agonist of protein kinase A (PKA), stimulated dopamine uptake in D8 cells and blocked apoptosis induced by the drug. These results suggest that the dopamine transporter mediates a dopamine-dependant apoptotic signal transduction pathway that is independent of dopamine uptake into the cell.

Animals↗

[Persistent ectopic pregnancy, report of seven cases].

OBJECTIVE: To investigate and evaluate the occurrence, diagnosis and treatment of persistent ectopic pregnancy. METHODS: 411 patients with ectopic pregnancy treated via laparoscopy or laparotomy between July 1995 and June 2000 were reviewed. The clinic manifestations of patients who were successfully treated by laparoscopic surgery and those with persistent ectopic pregnancy were analyzed by multivariate stepwise logistic regression. RESULTS: Seven cases with persistent ectopic pregnancy occurred after laparoscopic surgery with an incidence rate of 3.5%. Six cases had been treated by conservative approach and one case by tubectomy. Persistent ectopic pregnancy was diagnosed in two cases because of abdominal pain and intra-abdominal hemorrhage and in five cases because of plateauing beta-hCG titers. Two of the seven cases underwent a second time laparoscopic surgery and five were treated with methotrexate. The size of ectopic mass and the absence of villi by pathologic finding were relevant factors of persistent ectopic pregnancy. CONCLUSION: Small mass of ectopic pregnancy, short amenorrhea time, and biopsy specimens in which no villi are found are all warning indicators of persistent ectopic pregnancy. Close postoperative beta-hCG surveillance is critical for diagnosis and treatment.

Chorionic Gonadotropin, beta Subunit, Human↗

Sequential recruitment of steroid receptor coactivator-1 (SRC-1) and p300 enhances progesterone receptor-dependent initiation and reinitiation of transcription from chromatin.

Employing a cell-free chromatin transcription system that recapitulates progesterone receptor (PR)-mediated transcription in vivo, we have investigated further the coactivator functions of steroid receptor coactivator-1 (SRC-1) in terms of its functional domains as well as cooperation with other coactivators in PR transactivation. By analyzing wild-type and mutant SRC-1 with liganded PR in the chromatin transcription system in vitro, the basic helix-loop-helix/Per-Arnt-Sim domain, the p300-binding domain, and the carboxyl-terminal region (containing the PR-binding site) of SRC-1 were shown to be important for PR transactivation. Although in context of a synthetic promoter its histone acetyltransferase activity was nonessential for PR-mediated transcription, SRC-1 was observed to act synergistically with p300 to enhance PR transactivation from chromatin. Moreover, SRC-1 and p300 were found to function cooperatively to increase the efficiency of productive transcription initiation and reinitiation. Further analysis of synergism between SRC-1 and p300 revealed an obligatory "sequential" recruitment of SRC-1 and p300 to liganded PR. Efficient recruitment of p300 required the presence of SRC-1. In addition, functional analysis of SRC-2 and SRC-3 coactivators indicated that the SRC family modulated PR transactivation from chromatin by a similar mechanism.

Acetyltransferases↗

Cloning and expression of a single-chain catalytic antibody that acts as a glutathione peroxidase mimic with high catalytic efficiency.

Glutathione peroxidase (GPX) has a powerful role in scavenging reactive oxygen species. In previous papers we have developed a new strategy for generating abzymes: the monoclonal antibody with a substrate-binding site is first prepared, then a catalytic group is incorporated into the monoclonal antibody's binding site by using chemical mutation [Luo, Zhu, Ding, Gao, Sun, Liu, Yang and Shen (1994) Biochem. Biophys. Res. Commun. 198, 1240-1247; Ding, Liu, Zhu, Luo, Zhao and Ni (1998) Biochem. J. 332, 251-255]. Since then we have established a series of catalytic antibodies capable of catalysing the decomposition of hydroperoxides by GSH. The monoclonal antibody 2F3 was raised against GSH-S-2,4-dinitrophenyl t-butyl ester and exhibited high catalytic efficiency, exceeding that of rabbit liver GPX, after chemical mutation. To produce pharmaceutical proteins and to study the reason why it exhibits high catalytic efficiency, we sequenced, cloned and expressed the variable regions of 2F3 antibody as a single-chain Fv fragment (2F3-scFv) in different bacterial strains. The amounts of 2F3-scFv proteins expressed from JM109 (DE3), BL21 (DE3), and BL21 (coden plus) were 5-10%, 15-20% and 25-30% of total bacterial proteins respectively. The 2F3-scFv was expressed as inclusion bodies, purified in the presence of 8 M urea by Co(2+)-immobilized metal-affinity chromatography (IMAC) and renatured to the active form in vitro by gel filtration. The binding constants of the active 2F3-scFv for GSH and GSSG were 2.46 x 10(5) M(-1) and 1.03 x 10(5) M(-1) respectively, which were less by one order of magnitude than that of the intact 2F3 antibody. The active 2F3-scFv was converted into selenium-containing 2F3-scFv (Se-2F3-scFv) by chemical modification of the reactive serine; the GPX activity of the Se-2F3-scFv was 3394 units/micromol, which approaches the activity of rabbit liver GPX.

Amino Acid Sequence↗

Consistency of encoding in monkey visual cortex.

Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules.

Action Potentials↗

Peroxisome proliferator-activated receptor gamma ligands inhibit mitogenic induction of p21(Cip1) by modulating the protein kinase Cdelta pathway in vascular smooth muscle cells.

The cyclin-dependent kinase inhibitor p21(Cip1) is up-regulated in response to mitogenic stimulation in various cells. PPARgamma ligands troglitazone (TRO, 10 microm) and rosiglitazone (RSG, 10 microm) attenuated the induction of p21(Cip1) protein by platelet-derived growth factor (PDGF) and insulin without affecting cognate mRNA levels in rat aortic smooth muscle cells (RASMC). The protein kinase Cdelta (PKCdelta) inhibitor rottlerin also blocked the induction of p21(Cip1) protein, whereas the conventional PKC isotype inhibitor Gö 6976 had no effect. Kinetic studies using the protein synthesis inhibitor cycloheximide showed that TRO, RSG, and rottlerin shortened the half-life of p21(Cip1) protein. TRO, RSG, and rottlerin inhibited PDGF-induced expression of p21(Cip1), but they did not affect insulin-induced expression of p21(Cip1). Both ligands inhibited PKCdelta enzymatic activity in PDGF-stimulated RASMC but not in insulin-stimulated cells. Adenovirus-mediated overexpression of PKCdelta rescued the down-regulation of p21(Cip1) expression both by TRO and RSG in PDGF-treated RASMC. These data suggested that the PKCdelta pathway plays a critical role in PDGF-induced expression of p21(Cip1) in RASMC and may be the potential target for PPARgamma ligand effects. Src kinase-dependent tyrosine phosphorylation of PKCdelta was decreased substantially by TRO and RSG. Tyrosine phosphorylation and activation of c-Src in response to PDGF were unaffected by either PPARgamma ligand. Protein-tyrosine-phosphatase inhibitors sodium orthovanadate and dephostatin prevented PPARgamma ligand effects on PKCdelta tyrosine phosphorylation and enzymatic activity. Both inhibitors also reversed PPARgamma ligand effects on p21(Cip1) expression in PDGF-treated RASMC. PPARgamma ligands enhanced protein-tyrosine-phosphatase activity in RASMC, which may be the mechanism for decreased PKCdelta tyrosine phosphorylation and activity. PPARgamma ligands regulate p21(Cip1) at a post-translational level by blocking PKCdelta signaling and accelerating p21(Cip1) turnover.

Acetophenones↗

Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.

PURPOSE: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. RESULTS: Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. CONCLUSION: This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.

Adult↗

Enhanced auditory reversal learning by genetic activation of protein kinase C in small groups of rat hippocampal neurons.

The hippocampus has a central role in specific types of learning, but there is only limited evidence identifying the requisite molecular changes in ensembles of hippocampal neurons. To investigate the role of protein kinase C (PKC) pathways in hippocampal mediated learning, a constitutively active, catalytic domain of rat PKC betaII was delivered into hippocampal dentate granule neurons using a Herpes Simplex Virus (HSV-1) vector. This PKC causes a long-lasting, activation-dependent increase in neurotransmitter release from cultured cells. Activation of PKC pathways in a small percentage (< or =0.26%) of dentate granule neurons was sufficient to enhance rat auditory discrimination reversal learning. The affected neurons altered hippocampal physiology as revealed by elevated NMDA receptor densities in specific hippocampal areas. Thus, these results directly suggest that activation of PKC pathways in a specific hippocampal area alters rat auditory discrimination reversal learning. Because each rat may contain a unique pattern of affected neurons, there appears to be considerable flexibility and/or redundancy in the groups of neurons that can modify learning.

Animals↗

Generation of autologous Epstein-Barr virus-specific cytotoxic T cells for adoptive immunotherapy in solid organ transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorders (PTLD) affect 2%-27% of solid organ transplant (SOT) recipients. Adoptive immunotherapy may have therapeutic potential in this setting, but there is little experience in generating autologous EBV-specific cytotoxic T-cell lymphocytes (EBV-CTLs) from SOT recipients, and their efficacy and persistence in an immunosuppressed environment is unknown. METHODS: EBV-CTLs were generated from eight SOT recipients, using weekly stimulations with autologous lymphoblastoid cell lines (LCLs) and interleukin-2. CTL phenotype and function were evaluated in the presence of therapeutic concentration of cyclosporin A or FK506. RESULTS: In all cases, CTLs expanded with normal kinetics. The majority was CD3+CD8+ (mean, 76%), with less than 3% of natural killer cells. All ex vivo-generated CTLs produced significantly higher killing of autologous LCLs than of HLA-mismatched LCLs (mean, 56% vs. 14% at 20:1 ratio). No lysis of autologous or allogeneic PHA blasts was observed. The CTL expansion rate was reduced in a concentration-dependent manner in the presence of immunosuppressive drugs; however, neither lytic activity nor phenotype was affected. CONCLUSIONS: Using methods that are approved for clinical application, EBV-CTLs can be generated from SOT recipients, even those with frank lymphoma, or who are receiving immunosuppressive drugs. These CTLs retain their function in the presence of immunosuppressive agents. Although in vivo efficacy, safety, and persistence can be assessed only in clinical trials, our results suggest that CTLs can be effective for the treatment of PTLD, even when immunosuppression cannot be reduced because of the high risk of graft rejection.

Antibody Specificity↗

Potts model for exaggeration of a simple rumor transmitted by recreant rumormongers.

A simple rumor transmitted by recreant rumormongers is considered quantitatively. The simple message contained in the rumor is represented by a simple proposition that has been universally quantified. The operations to change the proposition by rumormongers are established. To describe the rumor's transmission along different channels mathematically, a spin chain is introduced, in which spins represent the operations. The addition of spins is established according to the laws of operations. The result of a rumor's transmission is given by the chain's spin sum. The model, which is favorable for a social prognostication, can determine quantitatively how the social guide and the competition among various opinions affect the exaggeration of the simple rumor transmitted by recreant rumormongers. It proves that the rumor forms Potts-like spin chains in the case with maximum information entropy. The approximate calculation shows that the rumor may be aggrandized little or aggrandized normally, even sometimes catastrophically. Moreover, the exaggeration is greater when the guide is larger and the competition is lower.

Journal Article↗

[Triptolide inhibits vascular endothelial growth factor expression and production by endothelial cells].

OBJECTIVE: To investigate the effect of triptolide on vascular endothelial growth factor (VEGF) expression and secretion by endothelial cells, and explore the mechanism of anti-proteinuric effect of triptolide on glomerular nephritis. METHOD: A human umbilical endothelium derived cell line (ECV-304) from American Type Culture Collection(ATCC) was used in this study. The effects of triptolide on VEGF mRNA expression, and intracellular protein production and secretion induced by PMA were measured by RT-PCR, flow cytometry and enzyme linked immunosorbent assay (ELISA). The effects of triptolide on endothelial c-jun/c-fos mRNA expression were investigated by RT-PCR. RESULTS: 100 ng/ml PMA significantly increased VEGF mRNA expression, intracellular production and secretion of VEGF in endothelial cells, while triptolide inhibited the effects of PMA in a dose-dependent manner. Moreover, triptolide dose-dependently inhibited endothelial c-jun/c-fos mRNA expression. CONCLUSION: Triptolide is a potent inhibitor of VEGF expression and production, suggesting that the inhibitory influence of triptolide on VEGF expression and production may be one of the mechanisms underlying its anti-proteinuric effect on glomerular nephritis. Triptolide might inhibit VEGF expression and production by interfering with transcription factor AP-1 formation.

Anti-Inflammatory Agents, Non-Steroidal↗

A new phenomenon in the induction period of the methane dehydroaromatization reaction.

The induction period of dehydroaromatization of methane to benzene over Mo/HZSM-5 had been investigated in real-time by the resonant-enhanced two-photon ionization (RE2PI) technique; it is remarkable that there is a small amount of benzene formed in the early stage of the induction period; we suggest that the trace amount of benzene was caused by the reduction of the original Mo6+ ion during the induction period and the Mo6+ species has a slight catalytic activity for methane-benzene conversion.

Journal Article↗

Multiple isoforms and an unusual cathodic isoform of creatine kinase from channel catfish (Ictalurus punctatus).

In vertebrates, the creatine kinase (CK) family consists of two cytosolic and two mitochondrial isoforms. The two cytosolic isoforms are the muscle type (M-CK) and the brain type (B-CK). Here we report multiple CK isoenzymes in the diploid channel catfish (Ictalurus punctatus) with one unusual cathodic isoform that was previously found only in pathological situations in human. The cathodic CK isoform existed only in the channel catfish stomach, ovary, and spleen, but not in any other species analyzed such as tilapia, smallmouth bass, chicken, or rat. Two genes encode the multiple forms of the channel catfish M-CK cDNAs. M-CK1 has three alleles, M-CK1.1, M-CK1.2, and M-CK1.3, while M-CK2 has just one allele as determined by analysis of 17 cDNA clones and by allele-specific PCR. M-CK1 encodes a protein of 381 amino acids and the M-CK2 cDNA encodes a protein of 380 amino acids. The two cDNAs shared an 86% identity and both have the nine diagnostic boxes for cytosolic CKs and thus are of cytosolic origin. The M-CK1 gene was isolated, sequenced, and characterized and its promoter should be useful for transgenic research for muscle-specific expression.

Amino Acid Sequence↗

Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell cycle regulators.

Peroxisome proliferator activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily. Ligand activation of PPARgamma has been shown to cause growth arrest in several human tumor cell types, but the underlying molecular mechanism has not been elucidated. We report here that the PPARgamma ligand troglitazone (TRO) inhibited MCF-7 cell proliferation by blocking events critical for G1 --> S progression. Flow cytometry demonstrated that TRO at 20 microM increased the percentage of cells in G1 from 51 to 69% after 24 h. Accumulation of cells in G1 was accompanied by an attenuation of Rb protein phosphorylation associated with decreased CDK4 and CDK2 activities. Inhibition of CDK activity by TRO correlates with decreased protein levels for several G1 regulators of Rb phosphorylation (cyclin D1, and CDKs 2, 4, and 6). Overexpression of cyclin D1 partially rescued MCF-7 cells from TRO-mediated G1 arrest. Targeting of G1 regulatory proteins, particularly cyclin D1, and the resulting induction of G1 arrest by TRO may provide a novel antiproliferative therapy for human breast cancer.

Annexin A5↗

Alpha4 integrin is expressed during peripheral nerve regeneration and enhances neurite outgrowth.

We have shown previously that repair in the peripheral nervous system is associated with a reversion to an embryonic pattern of alternative splicing of the extracellular matrix molecule fibronectin. One of the consequent changes is a relative increase in the number of fibronectins expressing the binding site for alpha4 integrins. Here we show that alpha4 integrins are expressed on dorsal root ganglion neuron cell bodies and growth cones in the sciatic nerve during regeneration and that the interaction of alpha4 integrin with alternatively spliced isoforms of recombinant fibronectins containing the alpha4 binding site enhances neurite outgrowth in dorsal root ganglion neurons. The pheochromocytoma (PC12) neuronal cell line, which normally extends neurites poorly on fibronectin, does so efficiently when alpha4 is expressed in the cells. Experiments using chimeric integrins expressed in PC12 cells show that the alpha4 cytoplasmic domain is necessary and sufficient for this enhanced neurite outgrowth. In both dorsal root ganglion neurons and PC12 cells the alpha4 cytoplasmic domain is tightly linked to the intracellular adapter protein paxillin. These experiments suggest an important role for alpha4 integrin and paxillin in peripheral nerve regeneration and show how alternative splicing of fibronectin may provide a mechanism to enhance repair after injury.

Alternative Splicing↗

Resonance Rayleigh scattering study of the interaction of heparin with some basic diphenyl naphthylmethane dyes.

In a near-neutral medium, a combination of heparin with some basic diphenyl naphthylmethane dyes such as victoria blue 4R (VB4R), victoria blue B (VBB), or night blue (NB) can result in a significant enhancement of resonance. Rayleigh scattering (RRS) and their maximum scattering wavelengths lambdamax appear at 523, 534, and 540 nm for VB4R, VBB, and NB, respectively. The characteristics of RRS spectra of the heparin-dye complexes, the influencing factors, and the optimum conditions of these reactions have been investigated. The RRS intensity is directly proportional to the concentration of heparin in the range of approximately 0 to 0.4 microg/mL for all systems. The methods exhibit high sensitivities, and the detection limits for heparin are 3.35 ng/mL for the VB4R system, 6.62 ng/ mL for the VBB system, and 6.29 ng/mL for the NB system. Because the VB4R system is the most sensitive, it was taken as an example to study the selectivity of the method. A new method for the determination of trace amounts of heparin based on RRS technique has been developed. Moreover, the enhancement reasons of RRS and the relationship between RRS spectral characteristics of the heparin-dye complex and its absorption spectra have been primarily discussed.

Benzhydryl Compounds↗