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Biomedical subjects

Ming Li

Publications and source records attributed to Ming Li.

At least 73 records · Page 4Linked to original sources

[Outcome of surgical management of renal cell carcinoma with renal vein or inferior vena cava tumor thrombus].

OBJECTIVE: To investigate the prognosis of surgical treatment for renal cell carcinoma with renal vein or inferior vena cava tumor thrombus. METHODS: Between August 1994 and July 2004, 33 patients with renal cell carcinoma with renal vein or inferior vena cava tumor thrombus underwent radical nephrectomy and thrombectomy. The study population included 26 male and 7 female. The median age was 60 years (20 - 82). Level of tumor thrombus was renal vein in 15 patients, infrahepatic (level I) in 9, intrahepatic (level II) in 5, suprahepatic (level III) in 1, and right atrial extension (level IV) in 3. Survival analysis was made with Kaplan-Meier method. RESULTS: Twenty-nine patients can be followed up. Fourteen patients were lost with a mean survival time of (16.4 +/- 2.9) months (1 - 42 months). Fifteen patients were survival with a mean follow-up of (17.3 +/- 4.6) months (3 - 67 months). One patient was lost on the second postoperative day. Three patients can not be followed up. The 5-year Kaplan-Meier survival rate was 16%. The mean survival time of patients with renal vein involvement [(49.9 +/- 9.8) months] versus level I [(16.7 +/- 1.9) months] was significantly different (P < 0.05). CONCLUSIONS: Radical nephrectomy plus thrombectomy is a valuable method for the treatment of renal cell carcinoma with renal vein or inferior vena cava involvement. Patients with renal vein tumor thrombus appear to have better survival compared to patients with inferior vena cava tumor thrombus.

Adult↗

Crystal structure of human pyrroline-5-carboxylate reductase.

Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Delta(1)-pyrroline-5-carboxylate (P5C) to proline using NAD(P)H as the cofactor. The enzymatic cycle between P5C and proline is very important for the regulation of amino acid metabolism, intracellular redox potential, and apoptosis. Here, we present the 2.8 Angstroms resolution structure of the P5CR apo enzyme, its 3.1 Angstroms resolution ternary complex with NAD(P)H and substrate-analog. The refined structures demonstrate a decameric architecture with five homodimer subunits and ten catalytic sites arranged around a peripheral circular groove. Mutagenesis and kinetic studies reveal the pivotal roles of the dinucleotide-binding Rossmann motif and residue Glu221 in the human enzyme. Human P5CR is thermostable and the crystals were grown at 37 degrees C. The enzyme is implicated in oxidation of the anti-tumor drug thioproline.

Amino Acid Sequence↗

Linking animal models of psychosis to computational models of dopamine function.

Psychosis is linked to dysregulation of the neuromodulator dopamine and antipsychotic drugs (APDs) work by blocking dopamine receptors. Dopamine-modulated disruption of latent inhibition (LI) and conditioned avoidance response (CAR) have served as standard animal models of psychosis and antipsychotic action, respectively. Meanwhile, the 'temporal difference' algorithm (TD) has emerged as the leading computational model of dopamine neuron firing. In this report TD is extended to include action at the level of dopamine receptors in order to explain a number of behavioral phenomena including the dose-dependent disruption of CAR by APDs, the temporal dissociation of the effects of APDs on receptors vs behavior, the facilitation of LI by APDs, and the disruption of LI by amphetamine. The model also predicts an APD-induced change to the latency profile of CAR--a novel prediction that is verified experimentally. The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations.

Action Potentials↗

Mutation on N-terminus of polyhydroxybutyrate synthase of Ralstonia eutropha enhanced PHB accumulation.

Polyhydroxyalkanoate (PHA) synthase is the central enzyme involved in the biosynthesis of PHA, a family of bacterial biodegradable polyesters. Due to its high variability, the N-terminal fragment of this enzyme was previously considered as unnecessary for a functionally active enzyme. In this study, polyhydroxybutyrate synthase from Ralstonia eutropha (PhbC(Re)) with a deletion on N-terminal 88 amino acid residues showed a significant reduced activity, as reflected by only 1.5% PHB accumulation compared with the wild type which produced 58.4% PHB of the cell dry weight. Whilst several site-specific mutagenesis results revealed the amphiphilic alpha-helix assembled by the amino acid region, D70-E88 played an important role in both maintaining the PHB synthase activity and regulating molecular weight and polydispersity of accumulated PHB homopolymer.

Acyltransferases↗

GM-CSF-surface-modified B16.F10 melanoma cell vaccine.

Through the specific and tight interaction between streptavidin and biotin, a novel platform was developed to allow for rapid (less than 2h), efficient and durable display of streptavidin-tagged bioactive GM-CSF on the surface of biotinylated B16.F10 tumor cells. This technology involved biotinylation of the cell membrane with a biotin derivative and surface modification of the biotinylated cells with the bi-functional fusion protein, streptavidin-tagged GM-CSF. Furthermore, the resultant GM-CSF-modified B16.F10 whole tumor cell vaccine could induce strong and long-lasting systemic protection against the wild-type tumor challenge. Therefore, the platform may represent a fast, efficient and safe approach for the whole tumor cell vaccination.

Animals↗

The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells.

Oxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer.

Antineoplastic Agents↗

Cold-inducible RNA binding protein is required for the expression of adhesion molecules and embryonic cell movement in Xenopus laevis.

We have previously shown that the Xenopus homologue of cold-inducible RNA binding protein, XCIRP-1, is required for the morphogenetic migration of the pronephros during embryonic development. However, the underlying molecular mechanisms remain elusive. Here, we report that XCIRP is essential for embryonic cell movement, as suppression of XCIRP by microinjection of anti-sense mRNA and morpholino antisense oligonucleotides (MOs) significantly reduced protein expression, inhibited the cell migration rate, and inhibited eFGF and activin-induced animal cap elongation. By immunoprecipitation and RT-PCR, we further showed that the mRNA of a panel of adhesion molecules, including alphaE- and beta-catenin, C- and E-cadherin, and paraxial proto-cadherin, are the targets of XCIRP. Consistently, in animal cap explant studies, suppression of XCIRP by MOs inhibited the expression of these adhesion molecules, while over-expression of sense XCIRP-1 mRNA fully rescued this inhibition. Taken together, these results suggest for the first time that XCIRP is required to maintain the expression of adhesion molecules and cell movement during embryonic development.

Animals↗

Full q-space analysis of x-ray scattering of multilamellar membranes at liquid-solid interfaces.

A method for analyzing the x-ray scattering of a stack of phospholipid membranes at the solid-liquid interface in excess water is presented. It is argued that bilayers near the substrate fluctuate less significantly than the ones away from it and, therefore, make a larger contribution to the specular reflection at the low index Bragg peaks. But the diffuse scattering due to thermal fluctuations corrupts the Bragg peaks at high angles so that the specular contribution is not clearly observable. In the midst the specular reflection and the diffuse scattering cannot be separated easily and must be analyzed simultaneously. The height-difference correlation function derived from a modified Caillé theory enables one to simulate the longitudinal and the transverse scans in the same theoretical framework to yield more reliable structural parameters. The theoretical apparatus is successfully applied to the experimental data on DOPC membranes.

Algorithms↗

[Prediction of the stage of patients with prostate cancer by the combination of serum prostate specific antigen and Gleason score].

OBJECTIVE: To explore the method of predicting the stage of prostate cancer with serum prostate-specific antigen (PSA) and pathological grade. METHODS: One hundred and eighty-seven patients were studied retrospectively with prostate cancer diagnosed by systemic biopsy in our hospital. The rank correlation analysis, rank sum test and stepwise discriminant multivariate analysis were used to assess the correlation of serum PSA level, ratio of free PSA to total PSA (FPSA/TPSA ratio) with Gleason score (GS) and stage. RESULTS: Serum PSA level increased with GS for prostate cancer patients (r = 0.369, P < 0.001). With increasing stage, serum PSA level and GS increased (r = 0.398, 0.530, P < 0.001). Overall, FPSA/TPSA ratio was not correlated with stage (P > 0.70), but a significant negative correlation was demonstrated between them when serum PSA < or = 10 microg/L (r = -0.600, P < 0.05). When serum PSA > 20 microg/L, 67% - 87% patients with prostate cancer may be stage C or D. The equation using serum PSA and GS to predict the stage of patients with prostate cancer was: x = -3.488 + 0.041 x PSA + 0.428 x GS. CONCLUSIONS: Serum PSA level is positively correlated with GS for prostate cancer patients. Serum PSA level and GS are positively correlated with stage. A negative correlation between FPSA/TPSA ratio and stage is demonstrated when serum PSA < or = 10 microg/L. The combination of serum PSA and GS may predict the stage of patients with prostate cancer.

Adult↗

Method for internal standard introduction for quantitative analysis using on-line solid-phase extraction LC-MS/MS.

A novel approach for on-line introduction of internal standard (IS) for quantitative analysis using LC-MS/MS has been developed. In this approach, analyte and IS are introduced into the sample injection loop in different steps. Analyte is introduced into the injection loop using a conventional autosampler (injector) needle pickup from a sample vial. IS is introduced into the sample injection loop on-line from a microreservoir containing the IS solution using the autosampler. As a result, both analyte and IS are contained in the sample loop prior to the injection into the column. Methodology allowed to reliably introduce IS and demonstrated injection accuracy and precision comparable to those obtained using off-line IS introduction (i.e., IS and analyte are premixed before injection) while maintaining chromatographic parameters (i.e., analyte and IS elution time and peak width). This new technique was applied for direct analysis of model compounds in rat plasma using on-line solid-phase extraction (SPE) LC-MS/MS quantification. In combination with on-line SPE, IS serves as a surrogate IS and compensates for signal variations attributed to sample preparation and instrumentation factors including signal suppression. The assays yielded accuracy (85-119%), precision (2-16%), and analyte recovery comparable to those obtained using off-line IS introduction. Furthermore, on-line IS introduction allows for nonvolumetric sample (plasma) collection and direct analysis without the need of measuring and aliquoting a fixed sample volume prior to the on-line SPE LC-MS/MS analysis. Therefore, this methodology enables direct sample (plasma) analysis without any sample manipulation and preparation.

Animals↗

Electrochemical growth of highly oriented organic-inorganic superlattices using solid-supported multilamellar membranes as templates.

Controllable depositing of relatively thick inorganic sublayers into organic templates to fabricate organic-inorganic superlattices is of great importance. We report a novel approach to fabricating phospholipid/Ni(OH)(2) superlattices by electrochemical deposition of the inorganic component into solid-supported multilamellar templates. The well-ordered and highly oriented multilamellar templates are produced by spreading small drops of lipid solution on silicon surfaces and letting the solvent evaporate slowly. The templates which are used as working electrodes preserve the lamellar structure in the electrolyte solution. The resulting superlattices are highly oriented. The thickness of the nickel hydroxide is controlled by the concentration of nickel ions in the electrolyte bath. The electron density profiles derived from the X-ray diffraction data reveal that the thickness of the nickel hydroxide sublayers increases from 15 to 27 A as the concentration of nickel nitrate increases from 0.005 mol/L to 0.08 mol/L. We expect that the new method can be extended to depositing a variety of inorganic components including metals, oxides, and semiconductors.

Journal Article↗

EFA6A enhances glioma cell invasion through ADP ribosylation factor 6/extracellular signal-regulated kinase signaling.

EFA6A, or Pleckstrin and Sec7 domain protein, is a member of guanine nucleotide exchange factors for ADP ribosylation factor 6 (ARF6). Whereas EFA6A is specifically expressed in the brain, little is known about its function in glial cells or glioma. Here we show that elevated EFA6A expression is detectable in both low-grade and high-grade human glioma tissues samples. To investigate the role of EFA6A in glioma carcinogenesis, we generated a human glioblastoma cell line which conditionally overexpresses EFA6A (U373-EFA6A). We showed that overexpression of EFA6A had no effect on cell proliferation, apoptosis, or cell cycle control. However, as shown by wound healing and in vitro cell invasion assays, it significantly enhanced the cell motility and invasiveness whereas silencing EFA6A by its dominant negative mutant EFA6A(E242K) produced opposite effects. We further showed that ARF6/extracellular signal-regulated kinase (ERK) signaling is required for the EFA6A-mediated cell invasion because both EFA6A(E242K) and ARF6 dominant negative mutant ARF6(T27N) markedly reduced the phosphorylated ERK level and EFA6A-mediated invasive capacity. Consistently, mitogen-activated protein kinase/ERK kinase inhibitor U0126 could abolish the EFA6A-induced cell invasion. These results suggest for the first time a potential role of EFA6A/ARF6/ERK signal cascade in glioma cell migration and invasion.

ADP-Ribosylation Factor 6↗

GOLD HULL AND INTERNODE2 encodes a primarily multifunctional cinnamyl-alcohol dehydrogenase in rice.

Lignin content and composition are two important agronomic traits for the utilization of agricultural residues. Rice (Oryza sativa) gold hull and internode phenotype is a classical morphological marker trait that has long been applied to breeding and genetics study. In this study, we have cloned the GOLD HULL AND INTERNODE2 (GH2) gene in rice using a map-based cloning approach. The result shows that the gh2 mutant is a lignin-deficient mutant, and GH2 encodes a cinnamyl-alcohol dehydrogenase (CAD). Consistent with this finding, extracts from roots, internodes, hulls, and panicles of the gh2 plants exhibited drastically reduced CAD activity and undetectable sinapyl alcohol dehydrogenase activity. When expressed in Escherichia coli, purified recombinant GH2 was found to exhibit strong catalytic ability toward coniferaldehyde and sinapaldehyde, while the mutant protein gh2 completely lost the corresponding CAD and sinapyl alcohol dehydrogenase activities. Further phenotypic analysis of the gh2 mutant plants revealed that the p-hydroxyphenyl, guaiacyl, and sinapyl monomers were reduced in almost the same ratio compared to the wild type. Our results suggest GH2 acts as a primarily multifunctional CAD to synthesize coniferyl and sinapyl alcohol precursors in rice lignin biosynthesis.

Alcohol Oxidoreductases↗

Density functional computations of enantioselective alkynylation of aldehyde catalyzed by chiral zinc(II)-complexes.

The enantioselective alkynylation of aldehyde catalyzed by chiral zinc(II)-complexes was studied by means of the density functional theory (DFT). All the structures were optimized completely at the B3LYP/6-31G(d,p) level. To obtain more exact energies, single-point energy calculations at B3LYP/6-31+G(d,p) level were carried out on the B3LYP/6-31G(d,p) geometries. As shown, this enantioselective alkynylation was endothermic. The chirality-determining step for the alkynylation was the formation of the catalyst-ethanol complexes and the transition states for this step involved a six-membered ring. The dominant products predicted theoretically were of (R)-chirality, in good agreement with experiment. [Structure: see text].

Aldehydes↗

Vitamin E inhibits hemolysis induced by hemin as a membrane stabilizer.

Hemin is a potential cytolytic agent. To test the effect of vitamin E on hemin-mediated permeability in cell membranes, sheep erythrocytes were chosen as an appropriate model to study hemolysis induced by hemin. Hemin-induced hemolysis but did not elicit lipid peroxidation in sheep erythrocytes. Vitamin E was effective in inhibiting hemin-mediated hemolysis. Both chromanol ring and the isoprenoid side chain of tocopherols were essential for inhibition of hemin-induced hemolysis. There was a strong correlation between the inhibitory effects of tocopherols on hemin-induced erythrocyte hemolysis and their effects on fluorescence anisotropy of cell membranes. Our results suggested that, in contrast to its antioxidant activity, vitamin E inhibits hemolysis induced by hemin as a membrane stabilizing agent.

Animals↗

A new function of a previously isolated compound that stimulates activation and differentiation of myogenic precursor cells leading to efficient myofiber regeneration and muscle repair.

Muscle repair following severe injury is slow and incomplete due to the limited regenerative capacity of muscles comprising the function. In this study, one pure compound structurally corresponding to triterpenoid, which can directly induce the activation, proliferation and maturation of quiescent satellite cells into myocytes in vitro, was isolated from Geum japonicum. The potential effect of this compound on myogenesis was further tested in repair of severe muscle injury. It was found that this compound could significantly stimulate the regenerative potential of the damaged muscle resulting in regeneration of myotubes and myotube bundles time-dependently replacing the damaged muscle tissues. This compound-mediated active regeneration of new myofibers repairing damaged muscles was probably due to its direct action on activation and proliferation of quiescent myogenic precursor cells and enhancement of their maturation into regenerating myotubes, as was demonstrated in our primary myogenic precursor cells culture experiments. The up-regulated expression of endogenous phospho-Akt1 in compound-treated myogenic precursor cells may also contribute to the process of myofiber regeneration and muscle repair probably via promoting myogenic cell survival capacity.

Animals↗