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Biomedical subjects

Yan Chen

Publications and source records attributed to Yan Chen.

At least 217 records · Page 12Linked to original sources
PubMed2004

[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↗
PubMed2004

[Study on genetic polymorphism of NQO1 and susceptibility to benzene poisoning].

OBJECTIVE: To explore the relationship between genetic polymorphism of NQO1 and susceptibility to benzene poisoning (BP). METHODS: The genetic polymorphism of NQO1 for 100 patients with benzene poisoning and 90 workers exposed to benzene who were engaged in the same working time and job title as patients with benzene poisoning were detected by PCR-RFLP. RESULTS: There was a 2.82-fold (95% CI: 1.42-5.58 ) increased risk of BP in the subjects with NQO1 C609T mutation genotype (T/T) compared with those carrying heterozygous (C/T) and wild type (C/C), and there was a 2.94-fold (95% CI: 1.25-6.90) increased risk of BP in the subjects with NQO1 C609T mutation genotype (T/T) compared with those carrying wild type (C/C) . There was a trend that the risk of BP in subjects with NQO1 C609T mutation genotype (T/T) was higher than those carrying heterozygous (C/T) and even higher than those carrying wild type (C/C) (chi2(trend) = 6.01, P = 0.014). CONCLUSION: The subjects with NQO1 C609T mutation genotype (T/T) were more susceptive to benzene and NQO1 is as a biomarker to assessment the risk of benzene poisoning for individual.

Benzene↗
PubMed2004

[Foodborne disease outbreaks in China from 1992 to 2001 national foodborne disease surveillance system].

OBJECTIVE: To study the foodborne disease outbreaks in the areas covered by National Foodborne Disease Surveillance System. METHODS: Total 13 provinces were included in the surveillance system, and the foodborne disease outbreaks data during 1992 to 2001 were collected. RESULTS: During 1992-2001, a total of 5770 outbreaks of foodborne disease were reported. These outbreaks caused a reported 162,995 persons to become ill. Among outbreaks for which the etiology was determined, bacterial pathogens caused the largest percentage of outbreaks (38.5%) and the largest percentage of cases (50.9%). Vibrio parahaemolyticus (31.1%) accounted for the largest number of outbreaks and cases. Chemical agents caused 37.5% of outbreaks and 28.6% of cases. CONCLUSION: More work needs to be done to improve the foodborne disease surveillance system.

China↗
PubMed2004

[Autoantibody against granulocyte-macrophage colony-stimulating factor and other serum markers in pulmonary alveolar proteinosis].

OBJECTIVE: To evaluate the application of serum markers in the diagnosis, monitoring and understanding of the mechanisms of pulmonary alveolar proteinosis (PAP), the levels of the autoantibody against granulocyte-macrophage colony-stimulating factor (anti-GM-CSF antibody), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other serum markers, lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA), were measured in patients with PAP. METHODS: Serum samples were taken from 17 PAP patients (16 idiopathic and 1 congenital PAP), 18 patients with other pulmonary diseases disease control) and 40 healthy volunteers (healthy control). Anti-GM-CSF antibody was measured with indirect enzyme-linked immunosorbent assay (ELISA). GM-CSF and CEA were measured with commercial ELISA kits. LDH was measured with a kinetic method. RESULTS: The absorbance at 450 nm of serum anti-GM-CSF antibody in the idiopathic PAP (I-PAP), disease control and healthy control were 1.263 +/- 0.047, 0.835 +/- 0.018 and 0.246 +/- 0.009 respectively. The sensitivity and specificity of anti-GM-CSF in the diagnosis of I-PAP were 93.8% and 100% respectively, if the cutpoint was set as 4 times the average value of the healthy control. GM-CSF was not detectable in most PAP and other samples except 3/17 of PAP and 1/19 of disease control. The serum level of LDH was increased in I-PAP patients and correlated with CEA (r = 0.518) and alveolar-artery oxygen gradient (r = 0.769). CEA was increased in I-PAP patients [(12.85 +/- 3.79) ng/ml] compared with disease control [(2.04 +/- 0.63) ng/ml] and health control [(1.46 +/- 0.34) ng/ml] and correlated with alveolar-artery oxygen gradient (r = 0.552). The LDH levels decreased after lavage therapy [(348.38 +/- 38.88), (242.88 +/- 30.71) U/L, P < 0.05]. CONCLUSIONS: The high sensitivity and specificity of anti-GM-CSF antibody make it a potential diagnostic serum marker for I-PAP. LDH and CEA are useful markers in evaluation of disease progression of PAP.

Adult↗
PubMed2003

Probing protein oligomerization in living cells with fluorescence fluctuation spectroscopy.

Fluorescence fluctuation spectroscopy provides information about protein interactions in the intercellular environment from naturally occurring equilibrium fluctuations. We determine the molecular brightness of fluorescent proteins from the fluctuations by analyzing the photon counting histogram (PCH) or its moments and demonstrate the use of molecular brightness in probing the oligomerization state of proteins. We report fluorescence fluctuation measurements of enhanced GFP (EGFP) in cells up to concentrations of 10 microM by using an improved PCH theory. The molecular brightness of EGFP is constant in the concentration range studied. The brightness of a tandem EGFP construct, which carries two fluorophores, increases by a factor of two compared with EGFP alone, demonstrating the sensitivity of molecular brightness as a probe for protein complex formation. Oligomerization of nuclear receptors plays a crucial role in the regulation of gene expression. We probe the oligomerization state of the testicular receptor 4 and the ligand-binding domains of retinoid X receptor and retinoic acid receptor by observing molecular brightness changes as a function of protein concentration. The large concentration range accessible by experiment allows us to perform titration experiments on EGFP fusion proteins. An increase in the molecular brightness with protein concentration indicates the formation of homocomplexes. We observe the formation of homodimers of retinoid X receptor ligand binding domain upon addition of ligand. Resolving protein interactions in a cell is an important step in understanding cellular function on a molecular level. Brightness analysis promises to develop into an important tool for determining protein complex formation in cells.

Animals↗
PubMed2003

Engineering the nonlinear phase shift.

We treat the nonlinear phase shift response in the weak perturbation limit as a linear digital filter that can be synthesized into the values of its poles and zeros and mapped onto an optical architecture. This procedure results in a significant enhancement in the nonlinear sensitivity with a response that is robust to frequency changes within the filter passband. A precompensation technique can be used to reduce distortions under strongly driven nonlinear operation to achieve a larger phase shift. We also show that nonlinear sensitivity improves with increasing filter group delay and can be increased within constant linear bandwidth by use of higher-order filters.

Journal Article↗
PubMed2003

Adeno-associated virus-mediated bone morphogenetic protein-4 gene therapy for in vivo bone formation.

Adeno-associated virus (AAV) is so far the most valuable vehicle for gene therapy because it has no association with immune response and human disease. The present study was conducted to investigate the feasibility of AAV-mediated BMP4 gene transfer for bone formation. In vitro study suggested that AAV-BMP4 vectors could transduce myoblast C2C12 cells and produce osteogenic BMP4. In vivo study demonstrated that new bone formation could be induced by direct injection of AAV-BMP4 into the skeletal muscle of immunocompetent rats. Histological analysis revealed that the newly formed bone was induced through endochondral mechanism. Immunohistochemical staining further demonstrated that AAV-BMP4 gene delivery could mediate long-term transduction, and the involvement of BMP4 expression was responsible for the endochondral ossification. This study is, to our knowledge, the first report in the field of AAV-based BMP gene transfer and should be promising for clinical orthopaedic applications.

Animals↗
PubMed2003

Steps of the acceptor invasion mechanism for HIV-1 minus strand strong stop transfer.

Minus strand strong stop transfer is obligatory for completion of HIV-1 minus strand synthesis. We previously showed evidence for an acceptor invasion-initiated mechanism for minus strand transfer. In the present study, we examined the major acceptor invasion initiation site using a minus strand transfer system in vitro, containing the 97-nucleotide full-length R region. A series of DNA oligonucleotides complementary to different regions of the cDNA was designed to interfere with transfer. Oligomers covering the region around the base of the TAR hairpin were most effective in inhibiting transfer, suggesting that the hairpin base is a preferred site for acceptor invasion. The strong pausing of reverse transcriptase at the base of the TAR and the concomitant RNase H cleavages 10-19 nucleotides behind the pause site correlated with the location of the invasion site. Oligomers closer to the 5'-end of R also inhibited transfer, though less effectively, presumably by blocking strand exchange and branch migration. We propose that pausing of reverse transcriptase at the base of TAR increases RNase H cleavages, creating gaps for acceptor invasion and transfer initiation. Strand exchange then propagates by branch migration, displacing the fragmented donor RNA, including the fragment at the 5' terminus. The primer terminus switches to the acceptor, completing the transfer. Nucleocapsid (NC) protein stimulated transfer efficiency by 5-7-fold. NC enhanced RNase H cleavages close to the TAR base, creating more effective invasion sites for efficient transfer. Most likely, NC also stimulates transfer by promoting strand exchange invasion and branch migration.

DNA, Complementary↗
PubMed2003

Construction of an EGF receptor-mediated histone H1(0)-based gene delivery system.

PURPOSE: To construct an EGF receptor (EGF-R)-mediated histone H1(0)-based gene delivery system for gene therapy. METHODS: A recombinant DNA containing histone H1(0), EGF-R ligand, and endosomalytic domains was constructed in a prokaryotic vector and expressed in E. coli. Expression of the beta-galactosidase (beta-gal) gene in the tumor cells and tissues was observed after transduction of the beta-gal gene packaged by purified fusion proteins in vitro and in vivo. RESULTS: As an extension of the research on previously reported chemically synthetic composite polypeptide gene delivery systems, this genetically engineered polypeptide has proved to be capable of targeting the beta-galactosidase (beta-gal) gene into EGF-R-positive cancer cells both in vitro and in vivo. We also studied the time course of beta-gal gene expression in tumor tissues delivered in vivo by this polypeptide vector. At 24 h after administration, expression of the beta-galactosidase gene in tumor reached peak levels. The dosage optimization of administered polyplex was also investigated. The optimal dose of polyplex per mouse was 1 microg DNA packaged by 3 microg of composite polypeptide. CONCLUSIONS: The genetically engineered polypeptide based on histone H1(0) is a promising gene delivery system targeting EGF-R.

Animals↗
PubMed2003

Effect of culture media on the chemical and physical characteristics of polysaccharides isolated from Poria cocos mycelia.

Mycelia of a wild strain Poria cocos were cultured in two media differing in one constituent: bran extract or corn steep liquor, and are designated as wb and wc, respectively. Six polysaccharide fractions were isolated sequentially from the two mycelia by 0.9% NaCl (PCM1), hot water (PCM2), 0.5 M NaOH (PCM3-I and -II) and 88% formic acid (PCM4-I and -II). Their chemical and physical characteristics were determined by infrared spectroscopy (IR), gas chromatography (GC), 13C NMR, light scattering (LS) and viscometry. The results indicated that wb-, wc-PCM1, and PCM2 were heteropolysaccharides mainly composed of alpha-D-glucose, mannose, and galactose, whereas wb-PCM3-I and wc-PCM3-I were mainly (1-->3)-alpha-D-glucans, and wb- and wc-PCM3-II, PCM4-I and PCM4-II were (1-->3)-beta-D-glucans. Interestingly, (1-->3) alpha- and (1-->3)-beta-D-glucans co-existed in the 0.5 M NaOH fraction and were separated individually into the two fractions (PCM3-I and PCM3-II) after neutralizing with acetic acid. The polysaccharides from wc-PCM cultured in media containing corn steep liquor contained relatively more protein. The polysaccharide fractions also existed in conformations including random coil (as in PCM0 and PCM1) and expanded chain (as in PCM3), and differed molecular mass. In addition, two exo-polysaccharides isolated from the two culture media by methanol precipitation (wb- and wc-PCM0) also differed in their monosaccharide composition.

Chemical Phenomena↗
PubMed2003

Transcriptional regulation of tristetraprolin by transforming growth factor-beta in human T cells.

Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine that plays a critical role in modulating immune response and inflammation. We employed the Affymetrix cDNA microarray system to detect genes whose expression is regulated by TGF-beta1 in a human T cell line HuT78. Tristetraprolin (TTP), a protein involved in the degradation of tumor necrosis factor-alpha (TNF-alpha) mRNA, was found to be up-regulated by TGF-beta. This up-regulation was confirmed by reverse transcriptase-PCR analysis that revealed a rapid and transient induction of TTP mRNA by TGF-beta 1 in HuT78 cells, primary human T cells, and THP-1 macrophage-monocyte cells. In addition, de novo protein synthesis was not required for this induction, suggesting that TTP is regulated by TGF-beta at the transcriptional level. To delineate the transcriptional regulation of the TTP gene, a 2.7-kb human TTP promoter region (-2682 to +56 bp relative to the transcription initiation site) was isolated. We found that this promoter was stimulated by TGF-beta 1 or a constitutively active TGF-beta type I receptor via TGF-beta-specific Smad proteins. Furthermore, a series of TTP promoter deletion constructs were used to localize the Smad-responsive region to the -583 to -263 bp portion of the promoter. In this region, the TTP promoter contained a stretch of putative Smad-binding elements that had a synergistic effect in mediating Smad activation of the promoter. These putative Smad-binding element-containing sequences were also able to bind Smad3 and Smad4 proteins purified in vitro. As TGF-beta- and TTP-deficient mice exhibit overlapping phenotypes manifested by multifocal inflammation and autoimmunity, our findings that TTP transcription is under the control of TGF-beta signaling would indicate a potential role of TTP in mediating the immune suppressive action of TGF-beta in vivo.

Cell Line↗
PubMed2003

Engineering the aveC gene to enhance the ratio of doramectin to its CHC-B2 analogue produced in Streptomyces avermitilis.

Avermectin and its analogues are produced by the actinomycete Streptomyces avermitilis and are major commercial products for parasite control in the fields of animal health, agriculture, and human infections. Historically, the avermectin analogue doramectin (CHC-B1), which is sold commercially as Dectomax is co-produced during fermentation with the undesired analogue CHC-B2 at a CHC-B2:CHC-B1 ratio of 1.6:1. Although the identification of the avermectin gene cluster has allowed for characterization of most of the biosynthetic pathway, the mechanism for determining the avermectin B2:B1 ratio remains unclear. The aveC gene, which has an essential role in avermectin biosynthesis, was inactivated by insertional inactivation and mutated by site-specific mutagenesis and error-prone PCR. Several unrelated mutations were identified that resulted in improved ratios of the desirable avermectin analogue CHC-B1, produced relative to the undesired CHC-B2 fermentation component. High-throughput (HTP) screening of cultures grown on solid-phase fermentation plates and analysis using electrospray mass spectrometry was implemented to significantly increase screening capability. An aveC gene with mutations that result in a 4-fold improvement in the ratio of doramectin to CHC-B2 was identified. Subsequent integration of the enhanced aveC gene into the chromosome of the S. avermitilis production strain demonstrates the successful engineering of a specific biosynthetic pathway gene to significantly improve fermentation productivity of a commercially important product.

Base Sequence↗
PubMed2003

Regulation of TG-interacting factor by transforming growth factor-beta.

TG-interacting factor (TGIF) is a transcriptional co-repressor that directly associates with Smad (Sma- and Mad-related protein) proteins and inhibits Smad-mediated transcriptional activation. By using Affymetrix (Santa Clara, CA, U.S.A.) oligonucleotide microarray analysis, we found that TGIF mRNA level was elevated by transforming-growth-factor-beta (TGF-beta) treatment in a human T-cell line, HuT78. Subsequent reverse-transcription PCR assays indicated that TGF-beta1 and activin were able to induce a rapid and transient increase in the level of TGIF in both HuT78 and HepG2 hepatoma cells. To analyse whether or not the regulation of TGIF mRNA occurs at the transcriptional level, a 2.4 kb human TGIF promoter was isolated. A primer extension assay was performed to localize the putative transcription initiation site of the promoter. When transiently expressed in HepG2 cells, this promoter was stimulated by TGF-beta1 and activin treatment in a time-dependent manner. A series of deletion mutants of the TGIF promoter were also generated to further characterize the TGF-beta responsive region of the promoter. In addition, expression of TGIF was able to cause a dose-dependent inhibition of TGF-beta and activin signalling. Taken together, these experiments indicated that TGIF is a novel transcriptional target of TGF-beta and activin signalling and is likely involved in a negative feedback loop to desensitize TGF-beta/activin action.

Base Sequence↗
PubMed2003

Identification of cervical cancer markers by cDNA and tissue microarrays.

The Pap test has effectively reduced the incidence and mortality of cervical cancer. However, because of the morphological basis of this test, sensitivity and specificity are less than ideal, a situation that complicates the clinical management of women diagnosed with low-grade cervical abnormalities. In an attempt to understand the molecular basis of cervical tumorigenesis and to discover molecular markers for accurate cervical cancer screening, we used cDNA microarrays containing >30,000 Unigene clones to examine the gene expression patterns of 34 cervical tissues from different clinically defined stages. It was found that global gene expression patterns separated normal cervical tissues and low-grade squamous intraepithelial lesions from cervical cancers and most of the high-grade squamous intraepithelial lesions (HSILs). Among the top 62 genes/(expressed sequence tags) that were overexpressed in tumors and HSIL tissues, 35 were confirmed using in situ hybridization on cervical tissue micorarrays. Many of these genes were overexpressed in high-grade dysplastic and malignant cervical epithelium or in stroma adjacent to the diseased tissues, with cellular proliferation and extracellular matrix-associated genes being the most common. In general, the extent of gene overexpression increased as the lesions progressed from low-grade squamous intraepithelial lesions to HSILs and finally to cancer. It is hoped that with additional development, some of these markers will improve the interpretation of cervical screening tests and provide useful information for patient management decisions.

Biomarkers, Tumor↗
PubMed2003

Self-assembly of novel [3]- and [2]rotaxanes based on donor-acceptor and hydrogen-bonding interactions. Intensified inter-ring repulsion interaction and shuttling behavior.

Three novel hetero[3]rotaxanes, which comprise one neutral tetraamide cyclophane, one tetracationic cyclophane, and one linear component, have been assembled by utilizing hydrogen-bonding and donor-acceptor interactions, through three neutral [2]rotaxanes as intermediates. Three tetracationic [2]rotaxanes are also prepared for property comparison. For all three linear components, diamide subunits, the hydrogen-bonding templating moieties, are introduced at the center of the molecules, while the electron-rich hydrogquinone subunits, the donor-acceptor interaction templates, are incorporated between the diamides and the triphenylmethyl stoppers. Compared with the reported [3]rotaxanes, the novel hetero[3]rotaxanes exhibit remarkably intensified spatial interaction between the two ring components, which had been proved by (1)H NMR and UV study. For the first time, inter-ring NOEs are observed for interlocked [3]rotaxanes.

Journal Article↗
PubMed2003

Inhibition of influenza infection by glutathione.

Infection by RNA virus induces oxidative stress in host cells. Accumulating evidence suggests that cellular redox status plays an important role in regulating viral replication and infectivity. In this study, experiments were performed to determine whether the thiol antioxidant glutathione (GSH) blocked influenza viral infection in cultures of Madin-Darby canine kidney cells or human small airway epithelial cells. Protection against production of active virus particles was observed at a low (0.05-0.1) multiplicity of infection (MOI). GSH inhibited expression of viral matrix protein and inhibited virally induced caspase activation and Fas upregulation. In BALB/c mice, inclusion of GSH in the drinking water decreased viral titer in both lung and trachea homogenates 4 d after intranasal inoculation with a mouse-adapted influenza strain A/X-31. Together, the data suggest that the thiol antioxidant GSH has an anti-influenza activity in vitro and in vivo. Oxidative stress or other conditions that deplete GSH in the epithelium of the oral, nasal, and upper airway may, therefore, enhance susceptibility to influenza infection.

Animals↗