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Biomedical subjects

Yang Liu

Publications and source records attributed to Yang Liu.

At least 289 records · Page 16Linked to original sources

[The adverse reactions of parenteral norvancomycin in 1031 patients].

OBJECTIVE: To investigate the safety of norvancomycin, and provide basis for its rational use in clinical practice. METHODS: We documented all adverse events occurred in inpatients who receive intravenous infusion of norvancomycin, then we evaluated the relationship between adverse events and norvancomycin and calculated the rates of adverse reaction. RESULTS: 1031 patients were enrolled in this study from March 2002 to June 2003 and 965 of them could be evaluated. 80 adverse reactions occurred in 965 patients who received norvancomycin, giving a total adverse reaction rate of 8.29%. The systemic adverse reactions included renal impairment (4.04%), hepatic impairment (2.38%) and allergic reaction (1.76%). 15 patients discontinued the treatment because of the adverse reaction. The rates were higher in patients who use other antimicrobial agents concomitantly or whose age >/= 60 years. The rates of renal impairment were higher in those with age >/= 60 years, and the rates of hepatic impairment were higher in whose received this agent longer than 14 days. These factors were independent risk factors (P < 0.05). CONCLUSIONS: The overall adverse reaction rate of norvancomycin was low. A few patients experienced drug-related reaction, most of these adverse reactions were mild and tolerable. The adverse reactions tended to occur in older patients, those who use other antibiotic concomitantly or those who receive this agent longer than 14 days.

Adolescent↗

Altered metabolism of dopamine in the midbrain of mice treated with tributyltin chloride via subacute oral exposure.

Tributyltin (TBT) compounds have been detected in fish and shellfish. One of the targets of TBT compounds is the central nervous system. Alterations in the levels of neurotransmitters and their metabolites, and ratios of the levels of neurotransmitters to those of their metabolites have been used as indexes of neurotoxicity. We evaluated the neurotoxicity of TBT compounds in mice following subacute oral exposure by determining the levels of neurotransmitters and their metabolites in discrete brain regions. Male BALB/c mice were exposed to 0, 1, 5, 25, or 125 ppm TBT chloride in their feed for one month. Following the treatment period, their brains were removed and dissected into the cerebrum, cerebellum, medulla oblongata, midbrain, corpus striatum and hypothalamus. The levels of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin, and 5-hydroxyindolacetic acid were determined in different brain regions by high-performance liquid chromatography (HPLC). The mean body weight of mice treated with 125 ppm TBT was significantly lower than that of the control from day 5 to day 16 during the treatment period. The HVA/DA ratio in the midbrain of the 125 ppm-treated group was significantly higher than those of other treatment groups, and tended to be higher than that of the control. TBT may affect DA metabolism in the brain, especially in the midbrain.

3,4-Dihydroxyphenylacetic Acid↗

[Analysis of bacterial composition of the pink mat from spectacles hot spring in Tengchong by culture-independent approach].

The bacterial composition of the pink mat was studied by culture-independent approach. 23 complete 16S rDNA sequences were obtained. According to the sequences alignment and analysis of comparability, the bacteria of the pink mat was consisted of Proteobacteria, Firmicutes, Bacteroidetes, Actinobacter, Deinococcus-thermus, Aquificals. And compared with bacterial composition of the mats from Octopus spring in Yellowstone Park and Haegindi and Fluidir spring, Olkelduhals, Grensdalur spring in Iceland, the pink mat in spectacles spring had highest bacterial diversity among them because it perhaps included lots of bacteria at lower temperature. And the result indicated the same community lived in the same niche and Aquficales was dominant group among bacterial composition of the mat in higher temperature and near-neutral hot spring.

Bacteria↗

Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases.

To investigate the significance of the SARS-associated coronavirus (SARS-CoV) antibody, detected by ELISA and indirect immunofluorescence assays (IFA) for the SARS-CoV Vero E6 cell lysates, in non-SARS subjects, 114 serum samples from healthy controls and 104 serum specimens from autoimmune disease patients were collected. The results of ELISA showed that among 114 sera from healthy controls, 4 (3.5%) were positive of SARS-CoV-IgG antibody and 114 (100%) were all negative of SARS-CoV-IgM antibody; the specificity of SARS-CoV-IgG antibody for SARS patients was 96.5%, but the specificity of both SARS-CoV-IgG and -IgM antibodies for SARS patients was 100%. In 58 cases with SLE, positive rates of SARS-CoV-IgG and -IgM antibodies were 32.8% (19/58) and 8.6% (5/58), respectively, in which 11 cases (19%) were positive of both SARS-CoV-IgG and -IgM antibodies; in 10 cases with SS, positive rate of both SARS-CoV-IgG and -IgM antibodies was 10% (1/10); in 16 cases with MCTD, positive rate of SARS-CoV-IgG was 37.5% (6/16), positive rate of both SARS-CoV-IgG and -IgM antibodies was 6.3% (1/16); in 20 cases with RA, one case was positive (5%) of SARS-CoV-IgG. However, of all samples with positive SARS-CoV-IgG and -IgM antibodies for autoimmune diseases and healthy controls, SARS-CoV RNA and antibodies were all negative by RT-PCR and IFA. All sera for negative or positive ELISA results were also negative or positive results using ELISA with Vero E6 cells lysates. These studies showed that SARS-CoV Vero E6 cell lysates for the ELISA to detect SARS-CoV antibodies could lead to the false-positive reactions or cross-reactions of SARS-CoV antibodies in non-SARS diseases and healthy controls, and the false-positive reactions or cross-reactions were related to Vero E6 cell lysates and autoantibodies in non-SARS population.

Animals↗

Photocurrent generation in multilayer self-assembly films fabricated from water-soluble poly(phenylene vinylene).

A novel, water-soluble, cationic PPV derivative poly[(2,5-bis(3-bromotrimethylammoniopropoxy)-phenylene-1,4-divinylene)-alt-1,4-(2,5-bis(2-(2-hydroxyethoxy)ethoxy))phenylene vinylene] (BH-PPV) has been synthesized by a Heck coupling reaction. Multilayered assemblies of the BH-PPV and the sodium salt of hexa(sulfobutyl)fullerenes (C(60)-HS) were fabricated successfully by an alternate deposition technique. The multilayer structures were studied by UV/Vis spectroscopy, small angle X-ray diffraction, and atomic force microscopy. The photoinduced charge transfer property of the self-assembled multilayer film was also measured by a three-electrode cell technique. A steady and rapid cathodic 5.5 microA cm(-2) photocurrent response was measured as the irradiation of the multilayer film was switched on and off. Importantly, the response of on/off cycling is prompt and reproducible. A possible mechanism for the electron-transfer process is proposed.

Journal Article↗

CD24 is a genetic modifier for risk and progression of multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine (CD24a) with valine (CD24v) in the mature protein. We found that the CD24v/v renders a >2-fold increase in the relative risk of MS in the general population (P = 0.023). Among familial MS, the CD24v allele is preferentially transmitted into affected individuals (P = 0.017). Furthermore, 50% of CD24v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24a/v (P = 0.00037) and CD24a/a (P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24a/a patients. Transfection with CD24a and CD24v cDNA demonstrated that the CD24v allele can be expressed at higher efficiency than the CD24a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.

Alanine↗

A "polyORFomic" analysis of prokaryote genomes using disabled-homology filtering reveals conserved but undiscovered short ORFs.

Prokaryote gene annotation is complicated by large numbers of short open reading frames (ORFs) that arise naturally from genetic code design. Historically, many hypothetical ORFs have been annotated as genes in microbes, usually with an arbitrary length threshold (e.g. greater than 100 codons). Given the use of such thresholds, what is the extent of genuine undiscovered short genes in the current sampling of prokaryote genomes? To assess rigorously the potential under-annotation of short ORFs with homology, we exhaustively compared the polyORFome--all possible ORFs in 64 prokaryotes (53 bacteria and 11 archaea) plus budding yeast--to itself and to all known proteins. The novelty of our analysis is that, firstly, sequence comparisons to/between both annotated and un-annotated ORFs are considered, and secondly a two-step disabled-homology filter is applied to set aside putative pseudogenes and spurious ORFs. We find that un-annotated homologous short ORFs (uhORFs) correspond to a small but non-negligible fraction of the annotated prokaryote proteomes (0.5-3.8%, depending on selection criteria). Moreover, the disabled-homology filter indicates that about a third of uhORFs correspond to putative pseudogenes or spurious ORFs. Our analysis shows that the use of annotation length thresholds is unnecessary, as there are manageable numbers of short ORF homologies conserved (without disablements) across microbial genomes. Data on uhORFs are available from http://pseudogene.org/polyo

Conserved Sequence↗

Purification and characterization of a novel carbaryl hydrolase from Aspergillus niger PY168.

A fungus capable of using carbaryl as the sole source of carbon and energy was isolated from a soil enrichment, and characterized as Aspergillus niger and designated strain PY168. A novel carbaryl hydrolase from cell extract was purified 262-fold to apparent homogeneity with 13.6% overall recovery. It had a monomeric structure with a molecular mass of 50,000 Da and a pI of 4.6, and the enzyme activity was optimal at 45 degrees C and pH 7.5, The activities were strongly inhibited by Hg(2+), Ag+, rho-chloromercuribenzoate, iodoacetic acid, diisofluorophosphate and phenylmethylsulfonyl fluoride but not EDTA and phenanthroline. The purified enzyme hydrolyzed various N-methylcarbamate insecticides. Carbaryl is the preferred substrate.

Aspergillus niger↗

Quartz crystal biosensor for real-time monitoring of molecular recognition between protein and small molecular medicinal agents.

A quartz crystal microbalance (QCM) biosensor integrated into a flow injection analysis (FIA) system was used for the real-time investigation of molecular recognition between a protein and small molecular medicinal agents. Two sulfa-drugs, sulfamethazine (SMZ) and sulfamethoxazole (SMO), were, respectively, immobilized on the gold electrodes of the piezoelectric crystals using appropriate procedures based on self-assembly of the dithiothreitol (DTT). The binding interactions of the two immobilized drug ligands, with various proteins in solution, were followed as changes in the resonant frequency of the modified crystals. Results obtained from this rapid screen analysis clearly indicated that the two drug ligands appeared quite different in this molecular recognition procedure although their structures were similar. SMZ-immobilized sensor showed specific interaction only with IgG, while SMO-immobilized sensor showed negligible specific binding with IgG, but binding with trypsin and chymotrypsin. Further studies on the specific interaction between immobilized SMZ and three different species of IgG--human IgG, goat IgG and mouse IgG were carried out and the marked species-dependent difference was observed. The resultant sensorgrams were rapidly analyzed by using an in-house kinetic analysis software based on genetic algorithm (GA) to derive both the kinetic rate constants (kass and kdiss) and equilibrium association constants (KA) for IgG-SMZ interactions. For the interactions, KA were 5.48 x 10(5), 2.75 x 10(5) and 1.86 x 10(5) M(-1) for human IgG, goat IgG and mouse IgG, respectively. The kinetic data provided further insight into the structural/functional relationships of different IgG on a molecular level.

Adsorption↗

Small heat shock protein Hsp16.3 modulates its chaperone activity by adjusting the rate of oligomeric dissociation.

Small heat shock proteins usually exist as oligomers and appear to undergo dynamic dissociation/reassociation, with oligomeric dissociation being a prerequisite for their chaperone activities. However, contradictory cases were also reported that chaperone activities could be enhanced with no change or even increase in oligomeric sizes. Using Hsp16.3 as a model system, our studies show the following: (1) Although a preheat (over 60 degrees C) treatment or the presence of low concentrations of urea (around 0.8M) hardly caused any change in the oligomeric size of Hsp16.3 proteins when examined by size exclusion chromatography, its chaperone activities were increased significantly. (2) Further analysis using the unique pore-gradient polyacrylamide gel electrophoresis revealed a dramatic increase in the tendency of oligomeric dissociation for both the preheated and urea-containing Hsp16.3. (3) Meanwhile, for both cases, an apparent increase in the rate constants of oligomeric dissociation was also observed, as determined by utilizing conjugated fluorescence probes whose quantum yield increases accompanying oligomeric dissociation. (4) Moreover, the fluorescence anisotropy analysis also demonstrated that the oligomeric structures for the preheated or urea-containing Hsp16.3 proteins seem to be more dynamic and variable. In light of these observations, we propose that the small heat shock proteins like Hsp16.3 can modulate their chaperone activities by adjusting the rate of oligomeric dissociation in responding to environmental changes. Results obtained here also suggest that small heat shock proteins might be able to "remember" their stress experiences via certain structural alterations which will allow them to act as better chaperones when the stress conditions reappear.

Acetates↗

Real time kinetic analysis of the interaction between immunoglobulin G and histidine using quartz crystal microbalance biosensor in solution.

Quartz crystal microbalance (QCM) biosensor integrated in a flow injection analysis (FIA) system was used for the investigation of the specific interaction between immunoglobin G (IgG) and histidine. The histidine was immobilized on the gold electrodes of the piezoelectric crystal using appropriate procedures based on self-assembling of the dithiothreitol (DTT). The specific interaction of the immobilized ligand with IgG in solution was followed as a change in the resonant frequency of the modified crystal and studied in real time without any additional labels. With the mass sensitive biosensor system, the differences in affinity of three different species of IgG: human IgG, goat IgG and mouse IgG were easily distinguished and their respective kinetic rate constants (kass and kdiss) and equilibrium association constants (KA) were determined from the curves of frequency versus time. For the interactions, KA were 2.92 x 10(4), 3.23 x 10(4) and 4.08 x 10(4) M(-1) for human IgG, goat IgG and mouse IgG, respectively.

Adsorption↗

On the role of unmutated antigens in tumor rejection in mice with unperturbed T-cell repertoires.

We investigate here whether P1A, which was the first CTL-recognized and unmutated tumor antigen to be identified, is a tumor rejection antigen for J558 plasmacytoma in mice with an unperturbed T-cell repertoire. We show that although transgenic mice expressing P1A in the thymus have almost complete deletion of P1A-reactive T cells, they reject the B7-1-transfected J558 at a rate comparable with wild-type mice. Thus, P1A is not a necessary tumor rejection antigen for the J558 tumor cells. On the other hand, if anti-P1A CTL response is sufficient for tumor rejection, tumor cells must lose the antigenic epitope to evade CTL destruction. To test this, we analyze whether tumor cells escaping J558-B7 immune spleen cells harbor mutations in the P1A epitope. We find that although the spleen contained a high proportion of P1A-reactive T cells, the recurrent tumor cells have no mutation in the P1A antigenic epitope and remain susceptible to lysis by P1CTL. Thus, the antigen-bearing tumor cells can evade immune destruction in the presence of a high number of P1A-reactive T cells. Taken together, our results demonstrate that in mice with a normal TCR repertoire, substantial numbers of P1A-reactive T cells are neither necessary nor sufficient for tumor rejection and raise interesting questions regarding the significance of T-cell response against unmutated tumor antigens.

Animals↗

Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment.

Little is known about the biochemical environment in phagosomes harboring an infectious agent. To assess the state of this organelle we captured the transcriptional responses of Mycobacterium tuberculosis (MTB) in macrophages from wild-type and nitric oxide (NO) synthase 2-deficient mice before and after immunologic activation. The intraphagosomal transcriptome was compared with the transcriptome of MTB in standard broth culture and during growth in diverse conditions designed to simulate features of the phagosomal environment. Genes expressed differentially as a consequence of intraphagosomal residence included an interferon gamma- and NO-induced response that intensifies an iron-scavenging program, converts the microbe from aerobic to anaerobic respiration, and induces a dormancy regulon. Induction of genes involved in the activation and beta-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of sigmaE-dependent, sodium dodecyl sulfate-regulated genes and genes involved in mycolic acid modification pointed to damage and repair of the cell envelope. Sentinel genes within the intraphagosomal transcriptome were induced similarly by MTB in the lungs of mice. The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment, showing it to be nitrosative, oxidative, functionally hypoxic, carbohydrate poor, and capable of perturbing the pathogen's cell envelope.

Animals↗

Two-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells.

Optimal activation of T cells requires delivery of both antigenic and costimulatory signals. It is unclear, however, if the function of the natural killer (NK) cells is also modulated by these 2 signals. Here we report that efficient control of solid allogeneic tumors by NK cells depends on codelivery of both B7-1 and major histocompatibility complex (MHC) class I on the tumor cells. The codelivery is required for optimal expansion and effector function of NK cells in response to both melanoma and plasmocytoma that expressed allogeneic MHC class I. Our results demonstrate that the 2 signals required for T-cell function also can regulate NK immunity and reveal an important similarity between the innate NK response and the adaptive T-cell response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Thermodynamics and kinetics of the hydride-transfer cycles for 1-aryl-1,4-dihydronicotinamide and its 1,2-dihydroisomer.

Five 1-(p-substituted phenyl)-1,4-dihydronicotinamides (GPNAH-1,4-H(2)) and five 1-(p-substituted phenyl)-1,2-dihydronicotinamides (GPNAH-1,2-H(2)) were synthesized, which were used to mimic NAD(P)H coenzyme and its 1,2-dihydroisomer reductions, respectively. When the 1,4-dihydropyridine (GPNAH-1,4-H(2)) and the 1,2-dihydroisomer (GPNAH-1,2-H(2)) were treated with p-trifluoromethylbenzylidenemalononitrile (S) as a hydride acceptor, both reactions gave the same products: pyridinium derivative (GPNA(+)) and carbanion SH(-) by a hydride one-step transfer. Thermodynamic analysis on the two reactions shows that the hydride transfer from the 1,2-dihydropyridine is much more favorable than the hydride transfer from the corresponding 1,4-dihydroisomer, but the kinetic examination displays that the former reaction is remarkably slower than the latter reaction, which is mainly due to much more negative activation entropy for the former reaction. When the formed pyridinium derivative (GPNA(+)) was treated with SH(-), the major reduced product was the corresponding 1,4-dihydropyridine along with a trace of the 1,2-dihydroisomer. Thermodynamic and kinetic analyses on the hydride transfer from SH(-) to GPNA(+) all suggest that the 4-position on the pyridinium ring in GPNA(+) is much easier to accept the hydride than the 2-position, which indicates that when the 1,4-dihydropyridine is used the hydride donor to react with S, the formed pyridinium derivative GPNA(+) may return to the 1,4-dihydropyridine by a hydride transfer cycle; but when the 1,2-dihydropyridine is used as the hydride donor, the formed pyridinium derivative can not return to the 1,2-dihydropyridine by the hydride reverse transfer from SH(-) to GPNA(+). These results clearly show that the hydride-transfer cycle is favorable for the 1,4-dihydronicotinamides, but unfavorable for the corresponding 1,2-dihydroisomers.

Electron Transport↗

Regulation of constitutive expression of mouse PTEN by the 5'-untranslated region.

PTEN tumor suppressor serves as a major negative regulator of survival signaling mediated by PI3 kinase/AKT/protein kinase B pathway, and is inactivated in various human tumors. Elucidation of mechanisms responsible for PTEN expression is important for providing insight into strategies to control the loss of PTEN expression in human cancers. Although recent studies suggested that p53 and Egr-1 can modulate induced PTEN expression, the mechanism responsible for ubiquitous constitutive expression of PTEN remains elusive. PTEN mRNA contains a highly conserved and GC-rich 5'-untranslated region (5'-UTR). Recently, it has been shown that the long 5'-UTR sequences of several growth-regulated mRNAs contain promoters that can generate mRNAs with shorter 5'-UTRs. In this paper, we tested whether the 5'-UTR sequence of mouse PTEN contains a promoter that is responsible for constitutive expression of PTEN. We found that the long 5'-UTR sequence of mouse PTEN severely inhibits translation of PTEN and a heterologous gene firefly luciferase. Deletion of the most 5'-UTR sequence would enhance translation efficiency 100-fold. We also showed that the 5'-UTR sequence of mouse PTEN does not have an internal ribosome entry site (IRES) that can mediate cap-independent initiation of translation. Instead, we found that the 5'-UTR sequence of mouse PTEN contains a strong promoter that drives the production of a transcript with shorter 5'-UTRs, which can be translated with higher efficiency. This promoter was mapped to the region between -551 and -220 bases upstream of the translation start codon. Cotransfection analysis using Drosophila SL2 cells showed that Sp1 is one of the major transcription factors that can constitutively activate this promoter. Two endogenous PTEN transcripts with 5'-UTRs of 193 and 109 bases were found in DU145 and H226 cell lines. Based on these observations, we conclude that the PTEN expression may be regulated at both transcriptional and translational levels, and that the 5'-UTR sequence of PTEN contains a promoter that is responsible for constitutive PTEN expression.

5' Untranslated Regions↗

CIITA-regulated plexin-A1 affects T-cell-dendritic cell interactions.

The major histocompatibility complex (MHC) class II transactivator (CIITA) is the 'master coactivator' of MHC class II genes. To identify new targets of CIITA, we analyzed cDNA microarrays of dendritic cells (DCs) from CIITA-deficient, MHC class II-deficient and control mice. We found the semaphorin receptor plexin-A1 was expressed in DCs, but not in other immune cells, and was strongly induced by CIITA. RNA interference by short hairpin RNA specific for plexin-A1, but not a single-nucleotide mutant, greatly reduced plexin-A1 expression and T cell stimulation by protein- or peptide-antigen-pulsed DCs.Plexin-A1 is not required for peptide binding to MHC. These data indicate involvement of plexin-A1 in T cell-DC interactions but not antigen processing or binding.

Animals↗

Novel sulfamethazine ligand used for one-step purification of immunoglobulin G from human plasma.

To replace conventional affinity ligand like protein A or protein G, a pseudobioaffinity ligand seems to be an alternative for the purification of immunoglobulin G (IgG). In this study, sulfamethazine (SMZ) was chosen as novel affinity ligand for investigating its affinity to human IgG. Monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) (PGMA) beads were employed as the support for high-performance affinity chromatography. SMZ was immobilized on PGMA beads using bisoxirane (ethanediol diglycigyl ether) as spacer. The resultant affinity media presented minimal non-specific interaction with other proteins. Results of high-performance frontal analysis indicated that the media showed specific affinity to human IgG with a dissociation constant on the order of 10(-6) M. The SMZ affinity column proved useful for a very convenient one-step purification of IgG from human plasma. Antibody purity after a one-step purification was higher than 90%, as determined by densitometric scanning of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified fraction under reducing condition. The results obtained indicate that SMZ is a valuable affinity ligand for purification of human IgG.

Chromatography, Affinity↗