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Biomedical subjects

Q Cheng

Publications and source records attributed to Q Cheng.

At least 19 recordsLinked to original sources

Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival.

AIMS: Several studies have analyzed the determinants of long-term survival in hilar cholangiocarcinoma (HCCA) patients, but the majority of these have not speculated adjuvant therapy on prognosis. We conduct this study to identify potential predictive factors for prognosis of HCCA focusing on aspects dealing with adjuvant therapy. PATIENTS AND METHODS: Data from 75 consecutive HCCA patients undergoing surgical resection with curative intent were recorded prospectively. The survivals of patients were comparable with respect to different factors followed by a univariate and multivariate analysis. RESULTS: Actual 1-year, 3-year, and 5-year survival rates were 84.0, 44.4 and 12.0%, respectively. By Cox proportional hazards survival analysis, the most powerful predictors of outcome was resection type (Hazard Ratio [HR] 17.4, 95% confidence interval [CI] 16.8-17.8), followed by adjuvant radiotherapy (RT) (HR 4.3, 95% CI 3.6-4.9), regional lymph nodes involvement (HR 2.1, 95% CI 1.7-2.6), and preoperative maximum serum total bilirubin level (HR 2.0, 95% CI 1.5-2.5). CONCLUSIONS: Our study showed overall a highly significant benefit in survival in favor of RT, and the difference was especially significant after R1/R2 resection and in patients with Bismuth III/IV type tumors. Postresection chemotherapy (CTx) did not show any clinical benefits. R0 resection still significantly improves survival. Lower total serum bilirubin level, no regional lymph nodes involvement conferred survival advantage.

Adult↗

A case-control study of Guillain-Barré syndrome in Harbin, China.

We evaluated the putative factors for the onset of Guillain-Barré syndrome (GBS) in Harbin, China by a case-control study based on the information from GBS patients identified from a population-based incidence survey, which is the first study of this kind in China. Sixty-nine GBS patients were identified during a 1-year period from 1 October 1997 to 30 September 1998, and they were matched with 69 controls for gender and age (+/-5 years). GBS diagnosis was validated by senior neurologists and GBS patients were followed up for 6 months after onset. Odds ratio (OR) and 95% confidence intervals (CI) for each putative factor for the onset of GBS were calculated and compared between GBS cases and controls. Precedent respiratory infections within 2 months before onset were found to be significantly more frequent in GBS patients than in controls (OR = 1.68, 95% CI: 1.21-2.33). Although the number of cases with gastroenteritis among GBS patients was more than double of that in the controls, the difference was not statistically significant (OR = 2.25, 95% CI: 0.73-6.96). Other putative factors as well as characteristics regarding family situation, education level, occupation, etc., were not found to be statistically different between GBS patients and controls.

Adolescent↗

Approximation of flammability region for natural gas-air-diluent mixture.

The growing implementation of exhaust gas recirculation (EGR) in reducing NO(x) emissions of engine is of paramount motivation to perform a fundamental research on the flammability characteristics of fuel-air-diluent mixtures. In this work, the influences of EGR on the flammability region of natural gas-air-diluent flames were experimentally studied in a constant volume bomb. An assumption of critical burning velocity at flammability limit is proposed to approximately determine the flammability region of these mixtures. Based on this assumption, an estimation of the flammability map for natural gas-air-diluent mixtures was obtained by using the empirical formula of burning velocity data. The flammability regions of natural gas-air mixtures with EGR are plotted versus the EGR rate. From the comparison of estimated results and experimental measurements, it is suggested that the accuracy of prediction is largely dependent upon the formula of burning velocity used. Meanwhile, the influence of pressure on the critical burning velocity at flammability limit is also investigated. On the basis of the pressure dependence criterion, the estimation was performed for the circumstance of high temperature and pressure, and the prediction results still agree well with those of experiments.

Air↗

Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid.

A significant increase in tumor regression was induced in N-nitroso-N-methylurea-induced mammary tumors in rats treated with the combination of melatonin and 9-cis-retinoic acid (9cRA). Treatment groups included: control (ethanolic saline), 9cRA (30 mg/kg chow/day), melatonin 500 microg/day, melatonin 1000 microg/day, melatonin 500 microg/day+9cRA and melatonin 1000 microg/day+9cRA. Rats treated with the lower dose of melatonin 500 microg+9cRA show the greatest degree of tumor regression (78%), with 54% undergoing complete regression and a significant increase in apoptotic cells observed by TUNEL Assay. Furthermore, tumor multiplicity and burden were significantly decreased by the combination of melatonin and 9cRA.

Alitretinoin↗

Experimental study of flammability limits of natural gas-air mixture.

Flammability limits data are essential for a quantitative risk assessment of explosion hazard associated with the use of combustible gas. The present work is to obtain the fundamental flammability data for prevention of the hazards in the practical applications. Experiments have been conducted in a constant volume combustion bomb, and the fuel considered here is natural gas (NG). The pressure histories in the combustion bomb are recorded and a criterion of 7% pressure rise has been used to judge a flammable mixture. The effects of ethane on NG-air flammability limits have been investigated. By adding diluent (carbon dioxide, nitrogen or their mixture) into NG-air mixture, the dilution effects on the flammability limits have been explored as well, and the results are plotted as functions of diluent ratio.

Air↗

Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice.

Factor XI (FXI) and factor IX (FIX) are zymogens of plasma serine proteases required for normal hemostasis. The purpose of this work was to evaluate FXI and FIX as potential therapeutic targets by means of a refined ferric chloride (FeCl(3))-induced arterial injury model in factor-deficient mice. Various concentrations of FeCl(3) were used to establish the arterial thrombosis model in C57BL/6 mice. Carotid artery blood flow was completely blocked within 10 min in C57BL/6 mice by application of 3.5% FeCl(3). In contrast, FXI- and FIX-deficient mice were fully protected from occlusion induced by 5% FeCl(3), and were partially protected against the effect of 7.5% FeCl(3). The protective effect was comparable to very high doses of heparin (1000 units kg(-1)) and substantially more effective than aspirin. While FXI and FIX deficiencies were indistinguishable in the carotid artery injury model, there was a marked difference in a tail-bleeding-time assay. FXI-deficient and wild-type mice have similar bleeding times, while FIX deficiency was associated with severely prolonged bleeding times (>5.8-fold increase, P < 0.01). Given the relatively mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable strategy for treating or preventing thrombus formation.

Animals↗

Novel beta-carotene ketolases from non-photosynthetic bacteria for canthaxanthin synthesis.

We reported previously that the Rhodococcus erythropolis strain AN12 synthesizes the monocyclic carotenoids 4-keto gamma-carotene and gamma-carotene. We also identified a novel lycopene beta-monocyclase in this strain. Here we report the identification of the rest of the carotenoid synthesis genes in AN12. Two of these showed apparent homology to putative phytoene dehydrogenases. Analysis of Rhodococcus knockout mutants suggested that one of them ( crtI) encodes a phytoene dehydrogenase, whereas the other ( crtO) encodes a beta-carotene ketolase. Expression of the beta-carotene ketolase gene in an Escherichia coli strain which accumulates beta-carotene resulted in the production of canthaxanthin. In vitro assays using a crude extract of the E. coli strain expressing the crtO gene confirmed its ketolase activity. A crtO homologue (DR0093) from Deinococcus radiodurans R1 was also shown to encode a beta-carotene ketolase, despite its sequence homology to phytoene dehydrogenases. The Rhodococcus and Deinococcus CrtO ketolases both catalyze the symmetric addition of two keto groups to beta-carotene to produce canthaxanthin. Even though this activity is similar to the CrtW-type of ketolase activity, the CrtO ketolases show no significant sequence homology to CrtW-type ketolases. The presence of six conserved regions may be a signature for the CrtO-type of beta-carotene ketolases.

Amino Acid Sequence↗

Asymmetrically acting lycopene beta-cyclases (CrtLm) from non-photosynthetic bacteria.

Carotenoids have important functions in photosynthesis, nutrition, and protection against oxidative damage. Some natural carotenoids are asymmetrical molecules that are difficult to produce chemically. Biological production of carotenoids using specific enzymes is a potential alternative to extraction from natural sources. Here we report the isolation of lycopene beta-cyclases that selectively cyclize only one end of lycopene or neurosporene. The crtLm genes encoding the asymmetrically acting lycopene beta-cyclases were isolated from non-photosynthetic bacteria that produced monocyclic carotenoids. Co-expression of these crtLm genes with the crtEIB genes from Pantoea stewartii (responsible for lycopene synthesis) resulted in the production of monocyclic gamma-carotene in Escherichia coli. The asymmetric cyclization activity of CrtLm could be inhibited by the lycopene beta-cyclase inhibitor 2-(4-chlorophenylthio)-triethylamine (CPTA). Phylogenetic analysis suggested that bacterial CrtL-type lycopene beta-cyclases might represent an evolutionary link between the common bacterial CrtY-type of lycopene beta-cyclases and plant lycopene beta- and epsilon-cyclases. These lycopene beta-cyclases may be used for efficient production of high-value asymmetrically cyclized carotenoids.

Amino Acid Sequence↗

Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naïve hosts.

Mathematical models of the in-host dynamics of malaria infections provide a valuable tool to explore aspects of the host-parasite interaction that are not possible to investigate experimentally. This paper presents predictions of several important parameter values for 2 parasite strains/groups: parasite PfEMP1 switching rates, dynamics of host anti-PfEMP1 antibodies and parameters related to specific and non-specific host immune responses. A stochastic simulation model of the in-host dynamics of Plasmodium falciparum infections in naïve hosts was used to make these predictions. This model incorporates a novel process to simulate antigenic variation by the parasite, and specific and non-specific immune responses by the host. Comparison of model output to a range of published statistics indicated that the model is capable of reproducing the features of clinical P. falciparum infections, including the characteristic recrudescent behaviour. Using the model, we explored the hypothesized switching mechanism of a fast overall rate of antigenic variation early in an infection and found that it is compatible with chronic infections when the var genes are split into 2 groups; fast and slow switching.

Animals↗

Origin and evolution of the light-dependent protochlorophyllide oxidoreductase (LPOR) genes.

Light-dependent NADPH-protochlorophyllide oxidoreductase (LPOR) is a nuclear-encoded chloroplast protein in green algae and higher plants which catalyzes the light-dependent reduction of protochlorophyllide to chlorophyllide. Light-dependent chlorophyll biosynthesis occurs in all oxygenic photosynthetic organisms. With the exception of angiosperms, this pathway coexists with a separate light-independent chlorophyll biosynthetic pathway, which is catalyzed by light-independent protochlorophyllide reductase (DPOR) in the dark. In contrast, the light-dependent function of chlorophyll biosynthesis is absent from anoxygenic photosynthetic bacteria. Consequently, the question is whether cyanobacteria are the ancestors of all organisms that conduct light-dependent chlorophyll biosynthesis. If so, how did photosynthetic eukaryotes acquire the homologous genes of LPOR in their nuclear genomes? The large number of complete genome sequences now available allow us to detect the evolutionary history of LPOR genes by conducting a genome-wide sequence comparison and phylogenetic analysis. Here, we show the results of a detailed phylogenetic analysis of LPOR and other functionally related enzymes in the short chain dehydrogenase/reductase (SDR) family. We propose that the LPOR gene originated in the cyanobacterial genome before the divergence of eukaryotic photosynthetic organisms. We postulated that the photosynthetic eukaryotes obtained their LPOR homologues through endosymbiotic gene transfer.

Amino Acid Sequence↗

Occurrence of Ross River virus and Barmah Forest virus in mosquitoes at Shoalwater Bay military training area, Queensland, Australia.

Shoalwater Bay military training area (SWBTA), 2,713 km2 of land located 50-80 km north of Rockhampton, Queensland, Australia, is used by Australian and allied forces for training purposes. Between March 1998 and February 2000, monthly collections of mosquitoes at 15 sites were conducted using carbon dioxide-baited traps to study the seasonal occurrence of mosquitoes and Ross River virus (RRV) and Barmah Forest virus (BFV) in mosquitoes. A total of 72,616 mosquitoes, comprising 3,897 pools were collected, and 2,428 pools were tested using a reverse transcriptase-polymerase chain reaction. A total of 15 pools of mosquitoes were positive for virus, 10 RRV and five BFV. Blood meals from an additional 763 mosquitoes were tested by a gel diffusion assay, and the majority (96%) of those identified were from kangaroo, which was the most common mammal in the study area. The results indicate that Culex annulirostris Skuse and Ochlerotatus vigilax (Skuse) are the main vectors of RRV at SWBTA.

Alphavirus↗

A small cryptic plasmid from Rhodococcus erythropolis: characterization and utility for gene expression.

Exploration of metabolically diverse rhodococci is generally hampered by the lack of genetic tools. A small cryptic plasmid (pAN12) isolated from Rhodococcus erythropolis strain AN12 was sequenced. Plasmid pAN12 encodes proteins that share homology to replication proteins and putative cell division proteins. Based on in vitro transposon mutagenesis, we determined that the Rep protein of pAN12 is essential for plasmid replication in Rhodococcus spp., and the putative cell division protein Div is important for plasmid stability. The pAN12 replicon is able to replicate in R. erythropolis strains AN12 and CW23 (ATCC 47072) and is compatible with the nocardiophage Q4 replicon present on a Rhodococcus shuttle plasmid pDA71. pAN12 appears to belong to the pIJ101/pJV1 family of rolling circle replication plasmids. Expression of an isoprenoid pathway gene ( dxs) on the pAN12-derived multicopy shuttle vector increased production of carotenoid pigments in R. erythropolis ATCC 47072.

Adenosine Triphosphatases↗

Overexpression of the MT1 melatonin receptor in MCF-7 human breast cancer cells inhibits mammary tumor formation in nude mice.

Overexpression of the MT1 melatonin receptor in MCF-7 human breast cancer cells significantly enhances the response of these cells to the growth-inhibitory actions of melatonin. Athymic nude mice implanted with MT1-overexpressing MCF-7 cells developed significantly fewer palpable tumors (60% reduction) compared to mice receiving vector-transfected MCF-7 cells (vt-MCF-7). In response to exogenous melatonin, tumor incidence in the mice receiving the MT1-overexpressing MCF-7 cells was decreased by 80% compared to mice receiving vt-MCF-7 cells. Interestingly, daily melatonin administration did not decrease tumor incidence in mice receiving vt-MCF-7 cells, but rather stimulated overall tumor formation.

Animals↗

Factor XI apple domains and protein dimerization.

The coagulation protease zymogen factor (F)XI is a disulfide bond-linked homodimer, a configuration that is necessary for protein secretion and function. The non-catalytic portion of the FXI polypeptide contains four repeats called apple domains (A1-A4). It is clear that FXI A4 plays a key role in dimer formation, however, the importance of other apple domains to this process has not been examined. We prepared recombinant FXI molecules in which apple domains were exchanged with those of the structurally homologous monomeric protein prekallikrein (PK). As expected, FXI/PK chimeras containing FXI A4 are dimers, while those with PK A4 are monomers. FXI A4 contains cysteine at position 321 that forms the interchain disulfide bond, while Cys321 in PK is unavailable for interchain bond formation because it is paired with Cys326. FXI/PK chimeras containing PK A4 were modified by changing Cys326 to glycine, leaving Cys321 unpaired (PKA4-Gly326). FXI with a PK A4 domain is a monomer, however, introducing PKA4-Gly326 results in a disulfide bond-linked dimer. This indicates that dimer formation can occur in the absence of FXI A4. In proteins containing PKA4-Gly326, replacing FXI A3 with PK A3 partially interferes with dimer formation, while substitution of A2, or A2 and A3 prevents dimer formation. PKA4-Gly326 cannot induce the native PK molecule to dimerize. The data indicate that FXI A2 and A3 make contributions to dimer formation. As these domains are involved in activities that require dimeric protein, it seems reasonable that they stabilize this conformation.

Binding Sites↗

New approaches for anti-infective drug discovery: antibiotics, vaccines and beyond.

Infectious disease is the leading cause of death worldwide, and billions of dollars are invested every year in developing anti-infective drugs. In the meantime, resistant bacteria are on the steady rise and render many once effective drugs useless. The tremendous funding and the urgent need to treat the resistant bacterial infections lead to the rapid progress on development of new drugs and potential new drug targets. New discoveries are being made that increase our understanding of microbial pathogenesis. Technological advancement is also being made to accelerate the drug discovery process. This review will mainly focus on discussing novel strategies on the development of antibiotics and vaccines for treating bacterial infections. Details of how some of the emerging technologies such as genomics and bioinformatics are accelerating the drug discovery process will be highlighted. Newly emerging concepts in controlling bacterial infections such as the use of probiotics and enzybiotics will also be briefly described.

Anti-Bacterial Agents↗

Purification, molecular characterization and reactivity with aromatic compounds of a laccase from basidiomycete Trametes sp. strain AH28-2.

A recently isolated basidiomycete, Trametes sp. strain AH28-2, can be induced to produce a high level of laccases when grown on a cellobiose-asparagine liquid medium. After induction by kraft lignin, two major isozymes were detected in the fermentation supernatant of the fungus. The principal component laccase A, which accounts for about 85% of the total activity, can be purified to electrophoretic homogeneity by three chromatographic steps: DEAE-Sepharose FF, Superdex-200 and Mono-Q. The solution containing purified laccase is blue in color, and the ratio of absorbance at 280 nm to that at 600 nm is 22. The molecular mass of laccase A is estimated to be 62 kDa by SDS-PAGE, 57 kDa by FPLC, and measured as 58522 Da by MALDI mass spectrum. Laccase A is a monomeric glycoprotein with a carbohydrate content of 11-12% and an isoelectric point of 4.2. The optimum pH and temperature for oxidizing guaiacol are 4.5 and 50 degrees C, respectively. The half-life of the enzyme at 75 degrees C is 27 min. The enzyme shows a good stability from pH 4.2 to pH 8.0. The K(m) values of the enzyme toward substrates 2,2'-azino-bis (3-ethylbenzothazoline-6-sulfonate) (ABTS), guaiacol and 2,6-dimethoxyphenol are 25, 420 and 25.5 microM, respectively, and the corresponding V(max) values are 670, 66.8, and 79 microM min(-1) x mg(-1), respectively. Laccase A activity is strongly inhibited by 0.1 mM NaN(3) or 0.1 mM cyanide. Two units of laccase A alone is able to completely oxidize 100 micromol 2,6-chlorophenol in 6 h. In the presence of 1 mM ABTS and 1-hydroxybenzotriazole, 15.0 U laccase A is able to oxidize 45% and 70% of 50 micromol fluorene in 12 and 18 h, respectively. The laccase A gene was cloned by a PCR method, and preliminary analysis of its sequence indicates 87.0% similarity to the corresponding segment in the phenoloxidase gene from Coriolus hirsutus.

Amino Acid Sequence↗

Biological conversion of cyclic alkanes and cyclic alcohols into dicarboxylic acids: biochemical and molecular basis.

Biological oxidation of cyclic alkanes and cyclic alcohols normally results in formation of the corresponding dicarboxylic acids, which are further metabolized in the cell. The biochemical pathways for oxidative conversion of cyclic compounds are similar in various phylogenetically diverse bacteria. Significant progress has been made in the past 2 years in the isolation and characterization of genes involved in cyclic alkane oxidation pathways in several bacterial species. In this article, we review recent advancements in the field of cyclic alcohol oxidation with focus on the biochemical and genetic characterization of the gene functions. Phylogenetic relationships of the analogous enzymes in the pathways are analyzed. Potential biocatalysis applications of these enzymes are also discussed.

Alcohols↗