Biomedical subjects

Hui Wang

Publications and source records attributed to Hui Wang.

At least 199 records · Page 11Linked to original sources

PubMed2005

Surveillance for antimicrobial resistance among clinical isolates of gram-negative bacteria from intensive care unit patients in China, 1996 to 2002.

The objective is to investigate the trend of antimicrobial resistance among nosocomial gram-negative bacteria isolated from intensive care units in China. From 1996 to 2002, the minimum inhibitory concentrations (MICs) of 8 antibiotics for 10,585 isolates of gram-negative bacteria from 19 hospitals in 7 central cities were determined by Etest. From 1996 to 2002, a marked decrease in the susceptibility of Pseudomonas aeruginosa to imipenem was noticed along the years (81-62%). Percentage of multidrug resistance of strains in P. aeruginosa obviously increased (11.5% in 1996, 20.5% in 2002). Imipenem kept active against Escherichia coli (99.2-100% susceptible), Acinetobacter spp. (97.6-93.5%), Klebsiella spp. (94.9-100%), Enterobacter spp. (89-96%). Resistance to cephalosporins, ciprofloxacin, and cefoperazone/sulbactam was observed, particularly among E. coli to ciprofloxacin (42-25%) and cefotaxime (78-54%) and Enterobacter spp. to ceftazidime (51-44%) and cefotaxime (50-37%). Piperacillin/tazobactam kept stable and active against P. aeruginosa, E. coli, and Klebsiella spp. (80%), with an increasing trend, but not good, in Enterobacter spp. (63-58%). Extended-spectrum beta-lactamase-producing strains in E. coli (28.6-45.7%) and Klebsiella spp. (25.5-34.9%) increased during 2001-2002. There was no significant increase resistance in Enterobacteriaceae isolates and Acinetobacter spp. to imipenem, but it has obviously decreased activity in P. aeruginosa throughout the 7-year period in China. Resistance of tested gram-negative bacteria to most comparator antimicrobials increased at different levels from 1996 to 2002 in China.

Anti-Bacterial Agents↗

PubMed2005

Role of VLA-4 and VLA-5 in ex vivo maintenance of human and pig hematopoiesis in human stroma-supported long-term cultures.

OBJECTIVE: The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environment. METHODS: Porcine and human c-kit+ bone marrow cells were purified and cultured on human bone marrow stroma for 6 weeks. The role of VLA-4 and VLA-5 in the maintenance of porcine vs human hematopoiesis in this human stroma-supported long-term bone marrow culture (LTBMC) system was evaluated by using blocking mAbs that bind to both species. RESULTS: Blocking VLA-4 with HP2/1 inhibited both human and porcine hematopoiesis, whereas anti-VLA-5 (SAM-1) suppressed the function of human, but not porcine, hematopoietic cells. In mixed LTBMC of porcine and human cells on a human stroma, porcine hematopoietic cells were at a competitive disadvantage, as seen by a rapid decline in cellularity, including clonogenic progenitors. This disadvantage was substantially overcome by the addition of SAM-1. Furthermore, human, but not porcine, cell adhesion to human fibronectin was inhibited by arginine-glycine-aspartic acid (RGD) peptides. CONCLUSION: Taken together, these results indicate that VLA-4 plays critical role for porcine hematopoiesis in a human hematopoietic environment, and raise the possibility that porcine VLA-5 might be unable to bind the respective human ligand and/or to initiate adequate post-ligand-binding signaling. Thus, VLA-5 may provide a potential target for developing approaches to improve porcine hematopoiesis in human recipients.

Animals↗

PubMed2005

Clinical evaluation of 546 tetracycline-stained teeth treated with porcelain laminate veneers.

OBJECTIVE: The purpose of this study was to evaluate the clinical result of 546 tetracycline-stained teeth restored with a porcelain laminate veneer system (Cerinate, Den-Mat, USA) for aesthetic reasons. METHODS: Tetracycline-stained teeth (546) were restored with a porcelain veneer system, and bonded with Ultra Bond resin cement. The restorations were recalled after 0.5, 1.5 and 2.5 years, respectively. Modified Ryge criteria were used to evaluate the veneers marginal adaptation, interfacial staining, secondary caries, postoperative sensitivity and the patients' satisfaction of the colour of the restorations. RESULTS: This study found that 99% veneers had excellent marginal adaptations; and less than 1% veneers required rebonding in the first 6 months; the colour of the veneers was stable and no evident staining was found. Almost all patients were satisfied with the colour match of their restorations 1 year after placement. CONCLUSIONS: The research indicated that the porcelain veneer restoration system under investigation provided a reliable and highly satisfactory choice for the aesthetic restoration of tetracycline-stained teeth.

Anti-Bacterial Agents↗

PubMed2005

Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea.

BACKGROUND & AIMS: We have developed a therapeutic strategy for gastrointestinal infections that is based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. The aim of this study was to apply this to the development of a recombinant probiotic for treatment and prevention of diarrheal disease caused by enterotoxigenic Escherichia coli strains that produce heat-labile enterotoxin. METHODS: This was achieved by expressing glycosyltransferase genes from Neisseria meningitidis or Campylobacter jejuni in a harmless Escherichia coli strain (CWG308), resulting in the production of a chimeric lipopolysaccharide capable of binding heat-labile enterotoxin with high avidity. RESULTS: The strongest heat-labile enterotoxin binding was achieved with a construct (CWG308:pLNT) that expresses a mimic of lacto-N-neotetraose, which neutralized > or = 93.8% of the heat-labile enterotoxin activity in culture lysates of diverse enterotoxigenic Escherichia coli strains of both human and porcine origin. When tested with purified heat-labile enterotoxin, it was capable of adsorbing approximately 5% of its own weight of toxin. Weaker toxin neutralization was achieved with a construct that mimicked the ganglioside GM2. Preabsorption with, or coadministration of, CWG308:pLNT also resulted in significant in vivo protection from heat-labile enterotoxin-induced fluid secretion in rabbit ligated ileal loops. CONCLUSIONS: Toxin-binding probiotics such as those described here have considerable potential for prophylaxis and treatment of enterotoxigenic Escherichia coli-induced travelers' diarrhea.

Adrenal Glands↗

PubMed2005

ANOSVA: a statistical method for detecting splice variation from expression data.

MOTIVATION: Many or most mammalian genes undergo alternative splicing, generating a variety of transcripts from a single gene. New information on splice variation is becoming available through technology for measuring expression levels of several exons or splice junctions per gene. We have developed a statistical method, ANalysis Of Splice VAriation (ANOSVA) to detect alternative splicing from expression data. Since ANOSVA requires no transcript information, it can be applied when the level of annotation is poor. When validated against spiked clone data, it generated no false positives and few false negatives. We demonstrated ANOSVA with data from a prototype mouse alternative splicing array, run against normal adult tissues, yielding a set of genes with evidence of tissue-specific splice variation. AVAILABILITY: The results are available at the supplementary information site. SUPPLEMENTARY INFORMATION: The results are available at the supplementary information site https://bioinfo.affymetrix.com/Papers/ANOSVA/

Alternative Splicing↗

PubMed2005

Under the genomic radar: the stealth model of Alu amplification.

Alu elements are the most successful SINEs (Short INterspersed Elements) in primate genomes and have reached more than 1,000,000 copies in the human genome. The amplification of most Alu elements is thought to occur through a limited number of hyperactive "master" genes that produce a high number of copies during long evolutionary periods of time. However, the existence of long-lived, low-activity Alu lineages in the human genome suggests a more complex propagation mechanism. Using both computational and wet-bench approaches, we reconstructed the evolutionary history of the AluYb lineage, one of the most active Alu lineages in the human genome. We show that the major AluYb lineage expansion in humans is a species-specific event, as nonhuman primates possess only a handful of AluYb elements. However, the oldest existing AluYb element resided in an orthologous position in all hominoid primate genomes examined, demonstrating that the AluYb lineage originated 18-25 million years ago. Thus, the history of the AluYb lineage is characterized by approximately 20 million years of retrotranspositional quiescence preceding a major expansion in the human genome within the past few million years. We suggest that the evolutionary success of the Alu family may be driven at least in part by "stealth-driver" elements that maintain low retrotranspositional activity over extended periods of time and occasionally produce short-lived hyperactive copies responsible for the formation and remarkable expansion of Alu elements within the genome.

Alu Elements↗

PubMed2005

Chromosomally located gene fusions constructed in Acinetobacter sp. ADP1 for the detection of salicylate.

Acinetobacter sp. ADP1 is a common soil-associated bacterium with high natural competency, allowing it to efficiently integrate foreign DNA fragments into its chromosome. This property was exploited to engineer salicylate-inducible luxCDABE and green fluorescent protein (GFP) variants of Acinetobacter sp. ADP1. Specifically, Acinetobacter sp. ADPWH_lux displayed the higher sensitivity when comparing the two variants (minimum detection c. 0.5-1 microM salicylate) and a faster turnover of the lux marker gene, making it suitable for whole-cell luminescence assays of salicylate concentration. In contrast, the longer maturation and turnover times of the GFP protein make the Acinetobacter sp. ADPWH_gfp variant more suited to applications involving whole-cell imaging of the presence of salicylate. The sensitivity of the luxCDABE variant was demonstrated by assaying salicylate production in naphthalene-degrading cultures. Assays using ADPWH_lux specifically mapped the kinetics of salicylate production from naphthalene and were similar to that observed by high-performance liquid chromatography (HPLC) data. However, ADPWH_lux exhibited the higher sensitivity, when compared with HPLC, for detecting salicylate production during the first 24 h of naphthalene metabolism. These data demonstrate that the engineered Acinetobacter variants have significant potential for salicylate detection strategies in laboratory and field studies, especially in scenarios where genetic stability of the construct is required for in situ monitoring.

Acinetobacter↗

PubMed2005

Alterations of placental cytochrome P450 1A1 and P-glycoprotein in tobacco-induced intrauterine growth retardation in rats.

AIM: To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1A1 (CYP1A1) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYP1A1 in tobacco smoke-induced intrauterine growth retardation (IUGR) in rats. METHODS: An IUGR model was produced by passive tobacco smoking from GD7 to parturition (GD21) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alteration and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYP1A1 and P-gp (mdr 1a and mdr 1b) were detected using a reverse transcription polymerase chain reaction and immunohistochemistry. RESULTS: Placental pathological changes occurred and the malondialdehyde content increased, whereas the activities of superoxide dismutase and CAT lowered, when compared to their controls. In the rat placenta of the tobacco group, the level of CYP1A1 mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD21 but not at GD14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta. CONCLUSION: The expression of placental CYP1A1 and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYP1A1 can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism, upregulation of P-gp might decrease tobacco exposure to a developing fetus with IUGR.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2005

Altered expression of cytochrome P450 and possible correlation with preneoplastic changes in early stage of rat hepatocarcinogenesis.

AIM: Correlation of cytochrome P450 (CYPs) with preneoplastic changes in the early stage of hepatocarcinogenesis is still unclear. To detect the expression of carcinogen-metabolizing related microsomal P450 enzymes, namely the CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, and CYP3A, we performed the medium-term bioassay of Ito's model in Sprague-Dawley rats. METHODS: The amount and activity of CYP were assessed by biochemical and immunohistochemical methods in week 8. The correlation between CYP expression and microsomal oxidative stress was investigated by comparing the generation of microsomal lipid peroxidation in the presence or absence of specific CYP inhibitor. RESULTS: In the DEN-2-AAF and 2-AAF alone groups, the expression of CYP1A1 and CYP2E1 were up-regulated and the expression of CYP2B1/2 and CYP1A2 were quite the contrary. Strong staining of CYP2E1 and CYP2B1/2 was found around the centrolobular vein and weak staining in the altered hepatic foci revealed by immunohistochemical procedure. There was no significant change in the activity of CYP3A among the 4 groups. Altered hepatic tissue bore more microsomal NADPH (nicotinamide adenine dinucleotide phosphate,reduced form)-dependent lipid peroxidation than normal tissue. And the difference among the 4 groups disappeared when CYP2E1 was inhibited. More microsomal lipid peroxidation was generated when incubated with CYP1A inhibitor a-naphthoflavone. CONCLUSION: CYP altered their expression levels and these alterations can play important roles in the alteration of cell redox status of preneoplastic tissue in the early stage of hepatocarcinogenesis.

2-Acetylaminofluorene↗

PubMed2005

Identification and characterization of cul-3b, a novel hominine CUL-3 transcript variant.

AIM: To identify genes related to the human testis development by substrate hybridization technique. METHODS: A human testis cDNA microarray was constructed and hybridized with probes prepared from human adult and fetal testes and spermatozoa mRNAs by reverse transcription reactions. The differentially expressed genes were sequenced. And a newly identified cullin-3 (CUL-3) transcript variant (designated cul-3b) was bio-informatically analyzed with an online GenBank database. Multi-tissue reverse transcription polymerase chain reaction (RT-PCR) was used to determine the tissue expression profile of cul-3b. RESULTS: Cul-3b, a novel CUL-3 transcript variant, was identified. The expression level of cul-3b in adult testes was 3.79-fold higher than that in fetal ones. Cul-3b differed from cul-3 (including NM_003590 and AY337761) in the opening reading frame and had three internal ribosomal entry sites IRESes in the 5'-UTR. These led to a 24 amino acid (aa) truncation at N-terminus of CUL-3b as compared with CUL-3 and a more motivated expression pattern of cul-3b under some strict circumstances. Additionally, cul-3b expressed ubiquitously in human tissues according to multi-tissue RT-PCR. CONCLUSION: Cul-3b is a novel transcript variant of CUL-3, which may be important not only for the development of human testis but also for that of other organs.

Base Sequence↗

PubMed2005

Expression of a novel dipeptidyl peptidase 8 (DPP8) transcript variant, DPP8-v3, in human testis.

AIM: To investigate the role of a novel dipeptidyl peptidase 8 transcript variant (DPP8-v3) gene in testis development and/or spermatogenesis. METHODS: A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and Southern-blot analysis. RESULTS: A new transcript variant of the human dipeptidyl peptidase (DPP8), exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 (DPP8-v3). The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. CONCLUSION: DPP8-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility.

Adult↗

PubMed2005

Effect of direct electric current on the cell surface properties of phenol-degrading bacteria.

The change in cell surface properties in the presence of electric currents is of critical concern when the potential to manipulate bacterial movement with electric fields is evaluated. In this study, the effects of different direct electric currents on the cell surface properties involved in bacterial adhesion were investigated by using a mixed phenol-degrading bacterial culture in the exponential growth phase. The traits investigated were surface hydrophobicity (measured by adherence to n-octane), net surface electrostatic charge (determined by measurement of the zeta potential), and the cell surface shape and polymers (determined by scanning electron microscope analysis). The results showed that a lower current (less than 20 mA) induced no significant changes in the surface properties of phenol-degrading bacteria, that an electric current of 20 mA could increase the surface hydrophobicity and flatten the cell shape, and that a higher current (40 mA) could increase the surface extracellular substances and the net negative surface electrostatic charge. The results also revealed that the electric current effects on cell hydrophobicity varied with the suspending medium. We suggest that an electric current greater than 20 mA is not suitable for use in manipulation of the movement of the phenol-degrading bacteria, although such a current might favor the electrophoretic movement of the bacterial species.

Bacteria↗

PubMed2005

Loss of complement activation and leukocyte adherence as Nippostrongylus brasiliensis develops within the murine host.

Complement activation and C3 deposition on the surface of parasitic helminths may be important for recruitment of leukocytes and for damage to the target organism via cell-mediated mechanisms. Inhibition of complement activation would therefore be advantageous to parasites, minimizing damage and enhancing migration through tissues. The aim of this study was to determine ex vivo if complement activation by, and leukocyte adherence to, the nematode Nippostrongylus brasiliensis change as the parasite matures and migrates through the murine host. Pathways of activation of complement and the mechanism of adherence of leukocytes were also defined using sera from mice genetically deficient in either C1q, factor B, C1q and factor B, C3, or C4. Substantive deposition of C3 and adherence of eosinophil-rich leukocytes were seen with infective-stage (L3) but not with lung-stage (L4) larvae. Adult intestinal worms had low to intermediate levels of both C3 and leukocyte binding. For L3 and adult worms, complement deposition was principally dependent on the alternative pathway. For lung-stage larvae, the small amount of C3 detected was dependent to similar degrees on both the lectin and alternative pathways. The classical pathway was not involved for any of the life stages of the parasite. These results suggest that in primary infections, the infective stage of N. brasiliensis is vulnerable to complement-dependent attack by leukocytes. However, within the first 24 h of infection, N. brasiliensis acquires the ability to largely avoid complement-dependent immune responses.

Animals↗

PubMed2005

Adenosine kinase inhibition and suppression of RNA silencing by geminivirus AL2 and L2 proteins.

Most plant viruses are initiators and targets of RNA silencing and encode proteins that suppress this adaptive host defense. The DNA-containing geminiviruses are no exception, and the AL2 protein (also known as AC2, C2, and transcriptional activator protein) encoded by members of the genus Begomovirus has been shown to act as a silencing suppressor. Here, a three-component, Agrobacterium-mediated transient assay is used to further examine the silencing suppression activity of AL2 from Tomato golden mosaic virus (TGMV, a begomovirus) and to determine if the related L2 protein of Beet curly top virus (BCTV, genus Curtovirus) also has suppression activity. We show that TGMV AL2, AL2(1-100) (lacking the transcriptional activation domain), and BCTV L2 can all suppress RNA silencing directed against a green fluorescent protein (GFP) reporter gene when silencing is induced by a construct expressing an inverted repeat GFP RNA (dsGFP). We previously found that these viral proteins interact with and inactivate adenosine kinase (ADK), a cellular enzyme important for adenosine salvage and methyl cycle maintenance. Using the GFP-dsGFP system, we demonstrate here that codelivery of a construct expressing an inverted repeat ADK RNA (dsADK), or addition of an ADK inhibitor (the adenosine analogue A-134974), suppresses GFP-directed silencing in a manner similar to the geminivirus proteins. In addition, AL2/L2 suppression phenotypes and nucleic acid binding properties are shown to be different from those of the RNA virus suppressors HC-Pro and p19. These findings provide strong evidence that ADK activity is required to support RNA silencing, and indicate that the geminivirus proteins suppress silencing by a novel mechanism that involves ADK inhibition. Further, since AL2(1-100) is as effective a suppressor as the full-length AL2 protein, activation and silencing suppression appear to be independent activities.

Adenosine Kinase↗

PubMed2005

Novel MDM2 p53-independent functions identified through RNA silencing technologies.

The MDM2 oncogene has an important role in human carcinogenesis and has been suggested as a novel target for cancer therapy. Many published in vitro and in vivo investigations have demonstrated that various MDM2 inhibitors including antisense oligonucleotides, siRNA, and small molecule MDM2 inhibitors have antitumor activity in in vitro and in vivo human cancer models, used alone or in combination with cancer chemotherapeutics and radiation therapy. For example, the mixed backbone antisense oligonucleotide developed in our laboratory specifically inhibited MDM2 expression in a dose- and time-dependent manner, resulting in significant antitumor activity in vitro and in vivo. Interestingly, the antisense MDM2 inhibitors have a broad spectrum of antitumor activities in human cancers, regardless of p53 status. These results prompted new investigations into the p53-independent functions of MDM2. This article summarizes the biochemical and molecular studies of the role of MDM2 in the regulation of p21 and E2F1 expression, stability and function, providing evidence for the utility of RNA-silencing technologies, including antisense oligonucleotides and siRNAs.

Animals↗

PubMed2005

Oncogenes as novel targets for cancer therapy (part I): growth factors and protein tyrosine kinases.

In the past 10 years, progress made in cancer biology, genetics, and biotechnology has led to a major transition in cancer drug design and development. There has been a change from an emphasis on non-specific, cytotoxic agents to specific, molecular-based therapeutics. Mechanism-based therapy is designed to act on cellular and molecular targets that are causally involved in the formation, growth, and progression of human cancers. These agents, which may have greater selectivity for cancer versus normal cells, and which may produce better anti-tumor efficacy and lower host toxicity, can be small molecules, natural or engineered peptides, proteins, antibodies, or synthetic nucleic acids (e.g. antisense oligonucleotides, ribozymes, and siRNAs). Novel targets are identified and validated by state-of-the-art approaches, including high-throughput screening, combinatorial chemistry, and gene expression arrays, which increase the speed and efficiency of drug discovery and development. Examples of oncogene-based, molecular therapeutics that show promising clinical activity include trastuzumab (Herceptin), imatinib (Gleevec), and gefitinib (Iressa). However, the full potential of oncogenes as novel targets for cancer therapy has not been realized and many challenges remain, from the validation of novel targets, to the design of specific agents, to the evaluation of these agents in both preclinical and clinical settings. In maximizing the benefits of molecular therapeutics in monotherapy or combination therapy of cancer, it is necessary to have an understanding of the underlying molecular abnormalities and mechanisms involved. This is the first part of a four-part review in which we discuss progress made in the last decade as it relates to the discovery of novel oncogenes and signal transduction pathways, in the context of their potential as targets for cancer therapy. This part delineates the latest discoveries about the potential use of growth factors and protein tyrosine kinases as targets for therapy. Later parts focus on intermediate signaling pathways, transcription factors, and proteins involved in cell cycle, DNA damage, and apoptotic pathways.

Animals↗

PubMed2005

Oncogenes as novel targets for cancer therapy (part II): Intermediate signaling molecules.

This is the second part of a four-part review on potential therapeutic targeting of oncogenes. The previous part introduced the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. This part of the review continues the exploration of various oncogenes, which we have grouped within seven categories: growth factors, tyrosine kinases, intermediate signaling molecules, transcription factors, cell cycle regulators, DNA damage repair genes, and genes involved in apoptosis. Part I included a discussion of growth factors and tyrosine kinases. This portion of the review covers intermediate signaling molecules and the various strategies used to inhibit their expression or decrease their activities.

Animals↗

PubMed2005

Oncogenes as novel targets for cancer therapy (part III): transcription factors.

This is the third paper in a four-part serial review on potential therapeutic targeting of oncogenes. The previous parts described the involvement of oncogenes in different aspects of cancer growth and development, and considered the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. This part of the review continues the exploration of various oncogenes that we have grouped within seven categories: growth factors, tyrosine kinases, intermediate signaling molecules, transcription factors, cell cycle regulators, DNA damage repair genes, and genes involved in apoptosis. Part one discussed growth factors and tyrosine kinases and part two discussed intermediate signaling molecules. This portion of the review covers transcription factors and the various strategies being used to inhibit their expression or decrease their activities.

Animals↗