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Biomedical subjects

Yu Chen

Publications and source records attributed to Yu Chen.

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

[Clinical and pathological characterization of antineutrophil cytoplasmic antibody associated small vasculitis in children].

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA) associated small vasculitides (ASV) are rare in children and often complicated in clinical manifestations and have very poor prognosis. In order to deepen our understanding of ANCA-associated small vasculitis (ASV) in children, the present study aimed to characterize their clinical manifestations, serum ANCA and renal histopathological findings and outcomes in Chinese children. METHODS: Serum ANCA was qualitatively tested with indirect immunofluorescence microscopy and anti-proteinase 3 (PR(3)) and anti-myeloperoxidase (MPO) activity were quantitated by enzyme-linked immunosorbent assays (ELISA), and renal biopsies were done to investigate the pathological changes. The clinical manifestation, serum ANCA and renal histopathological findings and outcome were characterized in 5 children with ANCA associated small vasculitis. RESULTS: (1) Five children with ANCA associated small vasculitis only accounted for 1.20% of children in whom renal biopsy was performed and 0.25% of hospitalized children with renal diseases during the same period. The age of onset of the 5 children with ASV was between 8 to 12 years with mean age 10.5 years. All ASV children were female. (2) All ASV children were negative for C-ANCA and showed normal anti-proteinase 3 activities, but positive for P-ANCA with high anti-myeloperoxidase activities between 98 to 242 kEU/L. The mean value of MPO-ANCA was 154.5 kEU/L (normal range < 12.7 kEU/L). (3) All ASV in the children was microscopic polyarteritis with wide-spread glomerular crescents formation and capillary tuft fibrinoid necrosis. Variety of complement C3 deposits and weak immunoglobulin deposits were noted in all ASV but one child who showed relatively strong deposits of IgA and IgM. The electronic dense deposits were mainly located in subendothelial space but were also found in the glomerular basement membrane in one child. (4) Three children with ASV died within one year after diagnosis, and two got remission and restored renal function after combined pulse therapy with methylprednisolone and cyclophosphamide (CTX), but remained to have hematuria and small amount of proteinuria after 1 and 5 year follow-up, respectively. CONCLUSION: Childhood ASV was female and P-ANCA predominant, more vulnerable to progress to renal failure and poorer in prognosis than adult cases. Qualitative and quantitative ANCA measurement and renal biopsy were key to the diagnosis of ASV in children.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2004

[Epidemiology and drug resistance of the pathogenic microbes in the complicated infection of hematological malignancies].

OBJECTIVE: To investigate the epidemiological characteristics and drug resistance profile of the infection in patients with hematological malignancies. METHODS: All the microbe strains isolated from the department of hematology in Ruijin hospital between 1998 and 2002 were collected for the assessment of antimicrobial susceptibility and the results were analysed by WHONET5 software. RESULTS: Out of the 536 strains isolated in the department of hematology, 230 (42.9%) were Gram positive and 301 (56.2%) Gram negative organisms. The first 6 strains of Gram (-) microbes in frequent order were Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Acinetobacter Baumannii and Stenotrophomonas (xantho) maltophi. The extended spectrum beta-lactamase (ESBLs) producing rates of Escherichia coli and Klebsiella pneumoniae were 27.3% and 33.3%, respectively. Methylcillin resistant coagulase negative staphylococcus (MRCNS) was the most prevalent Gram (+) bacteria in the complicated infection patients with hematological malignancies, which accounted for 88.5%. Carbapenems were most sensitive for all of the gram negative bacteria, with a drug resistance rate of 11.4 (5.0% approximately 15.8%) of imipenem. For ESBLs strains, carbapenems and cefapime were the best choice, with the resistance rate of 46.4% approximately 94.4% and 50.0% approximately 75.9%, respectively. The drug resistance rate of Acinetobacter Baumannii was 25.0% approximately 41.3% for the third generation cephalosporin, 22.7% for the fourth generation cephalosporin and 12.7% for imipenem. Pseudomonas aeruginosa was resistant to carbapenems, with a resistance rate of 12.7% of imipenem; however, it was more sensitive to the third generation cephalosporin. CONCLUSION: Antibiotics should be rationally administrated with more considerations to the characteristics of epidemiology and drug resistance profile of the microbes in the given department of hematology.

Bacterial Infections↗
PubMed2004

[Saline tolerance white clover transformed with the betaine aldehyde dehyrogenase gene by Agrobacterium tumefaciens].

The white clover has been transformed with the Betaine Aldehyde Dehydrogenase (BADH) gene cloned from Atriplex hortensis by Agrobacterium tumefaciens. The relative electronic conductivity of the transgenic plants under 1% NaCl stress for 48 hours was about 20%, less than the control plant's relative electronic conductivity (more than 40%), these showed the cell membrane of the transgenic plants has been less injured than control plants under salt stress. The other experience showed that the transgenic plant could grow well in water culture included 0.5% NaCl for more than two weeks, but the control plants could not.

Agrobacterium tumefaciens↗
PubMed2003

Suppression of the dual-specificity phosphatase MKP-1 enhances HIF-1 trans-activation and increases expression of EPO.

Hypoxia-inducible factor 1 (HIF-1) is a phosphorylated protein and its phosphorylation is involved in HIF-1alpha subunit stabilization as well as in the regulation of HIF-1 transcriptional activity. In a variety of cell lines, the phosphorylation of HIF-1alpha is dependent on ERK or p38, two members of the mitogen-activated protein kinase (MAPK) superfamily. In addition, active MAPK could be inactivated through dephosphorylation by mitogen-activated protein kinase phosphatase-1 (MKP-1). MKP-1 has been identified as a hypoxia responsive gene, but its role in the response of cells to hypoxia is poorly understood. Here we found that hypoxia induces MKP-1 expression in human hepatoma cells HepG2 in a time-dependent manner. Inhibition of MKP-1 expression using siRNA technique could enhance HIF-1alpha phosphorylation, accompanied by an increase in transcriptionally active HIF-1 as well as a rise in the levels of HIF-1-induced erythropoietin expression.

Carcinoma, Hepatocellular↗
PubMed2003

[Coronary artery bypass grafting in patients following percutaneous coronary interventions].

OBJECTIVE: To investigate and analyze the clinical outcomes of coronary artery bypass grafting (CABG) in patients with history of previous percutaneous coronary interventions (PCI). METHODS: We studied 76 patients with a history of PCI who underwent CABG surgery in our institute from August of 1999 to April of 2002, which was 14.0 percent of concurrent CABG. There were 39 cases with PTCA alone and 37 combined with stent implantation, of whom 5 had undergone re-do PCI therapy. Then 46 patients encountered re-stenosis and 6 developed new lesion in native coronary arteries. There were 4 cases with unsuccessful PCI, 11 cases with residual lesion in important vessels and 9 cases with acute complications during PCI. There was a higher incidence of myocardial infarction in group PCI than that in group Non-PCI, and a lower incidence of triple vessel disease (P<0.01). RESULTS: Group PCI had more emergent surgeries (27.6% vs 13.3%) and fewer OPCAB procedures (91.3% vs 97.2%) than group Non-PCI (P<0.01). The mean number of distal anastomosis in group PCI was smaller than that in group Non-PCI (P<0.01). There were 6 people who died in group PCI, of whom 3 died of heart pump failure,1 of ventricular fibrillation, 1 of neurological complication, and 1 of renal failure. The mortality of group PCI was higher than group Non-PCI (7.9% vs 1.9%, P<0.01). In group PCI, there were 4 with peri-operative myocardial infarction, 1 with late death and 1 with recurrent angina pectoris. CONCLUSION: CABG is usually the most effective and necessary way to treat PCI failure, unsatisfactory revascularization and its acute complications. It is most important to promptly and appropriately deal with acute complications of PCI in reducing the mortality.

Aged↗
PubMed2003

Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase.

Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. We examined whether genetic susceptibility, as determined by single nucleotide polymorphisms -463G-->A and -262C-->T in the oxidative stress genes myeloperoxidase (MPO) and catalase (CAT), respectively, are associated with the risk of arsenic-induced hyperkeratotic skin lesions-precursors of skin cancer-in a case-control study in Bangladesh. Carriers of the susceptible MPO and CAT genotypes were at elevated risk (OR 2.1 and 95% CI 0.7-6.2 for MPO; OR 1.9 and 95% CI 0.8-4.7 for CAT) of hyperkeratosis after adjustment for arsenic exposure and other covariates. Subjects carrying the high-risk MPO genotype and with high arsenic exposure were at almost six times (OR 5.8; 95% CI 1.1-30.1) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Similarly, highly exposed subjects carrying the high-risk CAT genotype were at more than four times (OR 4.6; 95% CI 1.4-15.6) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Our findings, although based on small numbers, suggest that the oxidative stress genes MPO and CAT may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions.

Adult↗
PubMed2003

Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction.

Transcription factors belonging to the FoxH1 and Mixer families are required for facets of Nodal signaling during vertebrate mesendoderm induction. Here, we analyze whether zebrafish proteins related to FoxH1 [Schmalspur (Sur)] and Mixer [Bonnie and clyde (Bon)] act within or downstream of the Nodal signaling pathway, test whether these two factors have additive or overlapping activities, and determine whether FoxH1/Sur and Mixer/Bon can account for all Nodal signaling during embryogenesis. We find that sur expression is independent of Nodal signaling and that bon is expressed in the absence of Nodal signaling but requires Nodal signaling and Sur for enhanced, maintained expression. These results and the association of FoxH1 and Mixer/Bon with phosphorylated Smad2 support a role for these factors as components of the Nodal signaling pathway. In contrast to the relatively mild defects observed in single mutants, loss of both bon and sur results in a severe phenotype characterized by absence of prechordal plate, cardiac mesoderm, endoderm and ventral neuroectoderm. Analysis of Nodal-regulated proteins reveals that Bon and Sur have both distinct and overlapping regulatory roles. Some genes are regulated by both Bon and Sur, and others by either Bon or Sur. Complete loss of Nodal signaling results in a more severe phenotype than loss of both Bon and Sur, indicating that additional Smad-associated transcription factors remain to be identified that act as components of the Nodal signaling pathway.

Animals↗
PubMed2003

F-actin and myosin II binding domains in supervillin.

Detergent-resistant membranes contain signaling and integral membrane proteins that organize cholesterol-rich domains called lipid rafts. A subset of these detergent-resistant membranes (DRM-H) exhibits a higher buoyant density ( approximately 1.16 g/ml) because of association with membrane skeleton proteins, including actin, myosin II, myosin 1G, fodrin, and an actin- and membrane-binding protein called supervillin (Nebl, T., Pestonjamasp, K. N., Leszyk, J. D., Crowley, J. L., Oh, S. W., and Luna, E. J. (2002) J. Biol. Chem. 277, 43399-43409). To characterize interactions among DRM-H cytoskeletal proteins, we investigated the binding partners of the novel supervillin N terminus, specifically amino acids 1-830. We find that the supervillin N terminus binds directly to myosin II, as well as to F-actin. Three F-actin-binding sites were mapped to sequences within amino acids approximately 280-342, approximately 344-422, and approximately 700-830. Sequences with combinations of these sites promote F-actin cross-linking and/or bundling. Supervillin amino acids 1-174 specifically interact with the S2 domain in chicken gizzard myosin and nonmuscle myosin IIA (MYH-9) but exhibit little binding to skeletal muscle myosin II. Direct or indirect binding to filamin also was observed. Overexpression of supervillin amino acids 1-174 in COS7 cells disrupted the localization of myosin IIB without obviously affecting actin filaments. Taken together, these results suggest that supervillin may mediate actin and myosin II filament organization at cholesterol-rich membrane domains.

Actins↗
PubMed2003

DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosis.

Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. An estimated 50-70 million people in Bangladesh have been chronically exposed to arsenic from drinking water and are at risk of skin and other cancers. We undertook the first study to examine whether genetic susceptibility, as determined by the codon 751 SNP (A-->C) of the DNA repair gene XPD, influences the risk of arsenic-induced hyperkeratotic skin lesions, precursors of skin cancer, in a case-control study of 29 hyperkeratosis cases and 105 healthy controls from the same community in an area of Bangladesh. As expected, there was a monotonic increase in risk of hyperkeratosis in relation to urinary arsenic measures but the XPD genotype was not independently associated with the risk. However, the increase in hyperkeratosis risk in relation to urinary arsenic measures genotype was borderline significant for urinary total arsenic (P for trend=0.06) and statistically significant for urinary creatinine adjusted arsenic (P for trend=0.01) among subjects with the XPD A allele (AA) but not among subjects with the other XPD genotypes. Among AA carriers, the risk for the highest arsenic exposed group compared with the lowest was more than 7-fold for urinary total arsenic and about 11-fold for urinary creatinine adjusted arsenic. In conclusion, our findings suggest that the DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. Future larger studies are needed to confirm this novel finding and investigate how combinations of different candidate genes and/or other host and environmental factors may influence the risk of arsenic induced skin and other cancers.

Adult↗
PubMed2003

Polycyclic aromatic hydrocarbon-DNA adducts among rickshaw drivers in Dhaka City, Bangladesh.

This paper describes findings from a recently completed study of polycyclic aromatic hydrocarbon (PAH) exposure among city dwellers of Dhaka, Bangladesh. We measured PAH-DNA adducts in white blood cells (WBCs) as a marker of environmental and occupational PAH exposure in 46 rickshaw drivers (who pedal commercial unshielded three-wheelers for passenger transport) and 48 non-rickshaw drivers (comparison group) in Dhaka city. We performed enzyme-linked immunosorbent assay (ELISA) to quantify immunologically the WBC PAH-DNA adducts. Rickshaw drivers had a significantly higher WBC PAH-DNA adducts level than the non-rickshaw drivers. Among rickshaw drivers, adduct levels tended to be positively associated with the duration of residence in the city and cigarette smoking. No such trends were observed among non-rickshaw drivers. In conclusion, the results suggest that urban residents who are occupationally exposed to traffic pollution in Dhaka are at potentially higher risk of health effects from exposure to carcinogenic PAH compounds.

Adult↗
PubMed2003

Synthesis and nonlinear optical properties of fluorine-containing naphthalocyanines.

The fluorine-containing metal naphthalocyanines [F16NcGaCl] (7) and [(F16NcGa)2O] (8), which represent the first examples of peripherally fluorine substituted naphthalocyanines, were synthesized, and the nonlinear optical transmission was studied. Peripheral substitution by fluorine atoms enhances the solubility and photostability of the naphthalocyanines. In particular, for the axially mu-oxo-bridged naphthalocyanine dimer 8, practically no aggregation was observed in organic solvents and it has proved to be an efficient optical limiter when irradiated with laser light pulses at the wavelength of 532 nm, with pulse duration of 5 ns and repetition rate of 20 Hz.

Cyanides↗
PubMed2003

The role of the conserved Trp330 in Flp-mediated recombination. Functional and structural analysis.

The active site of Flp contains, in addition to a transdonated nucleophilic tyrosine, five other residues that are highly conserved within the lambda-integrase family of site-specific recombinases and the type IB topoisomerases. We have used site-directed mutagenesis and x-ray crystallography to investigate the roles of two such residues, Lys223 and Trp330. Our findings agree with studies on related enzymes showing the importance of Lys223 in catalysis but demonstrate that in Flp-mediated recombination the primary role of Trp330 is architectural rather than catalytic. Eliminating the hydrogen bonding potential of Trp330 by phenylalanine substitution results in surprisingly small changes in reaction rates, compared with dramatic decreases in the activities of W330A, W330H, and W330Q. The structure of a W330F mutant-DNA complex reveals an active site nearly identical to that of the wild type. The phenylalanine side chain preserves most of the van der Waals interactions Trp330 forms with the Tyr343-containing trans helix, which may be particularly important for the docking of this helix. Our studies of Trp330 provide the first detailed examination of this conserved residue in the lambda-integrase family, suggesting that the relative importance of active site residues may differ among Flp and related enzymes.

Bacterial Proteins↗
PubMed2003

Solid-phase synthesis of pyrazolines and isoxazolines with sodium benzenesulfinate as a traceless linker.

[reaction: see text] The preparation of pyrazoline and isoxazoline derivatives with traceless solid-phase sulfone linker strategy is described. Key steps involved in the solid-phase synthetic procedure include (i) sulfinate S-alkylation, (ii) sulfone anion alkylation, (iii) gamma-hydroxy sulfone --> gamma-ketosulfone oxidation, and (iv) traceless product release via elimination-cyclization. A library of 12 pyrazolines and isoxazolines was synthesized.

Journal Article↗
PubMed2003

Correlation between near-infrared spectroscopy and magnetic resonance imaging of rat brain oxygenation modulation.

We measure the tissue oxygen and haemoglobin concentrations in the rat brain during modulation of inhaled oxygen concentration (FiO2), using non-invasive frequency domain near-infrared oximetry. The rise in oxygenated haemoglobin concentration and the decline in deoxygenated haemoglobin concentration are demonstrated in correspondence with the modulation of FiO2, which is changed from 20% to 100% in increments of 20%. Furthermore, the tissue oxygenation saturation also shows the corresponding trend and changes ranging from approximately 70% to 90%. The relative changes in deoxygenated haemoglobin concentration are compared to the blood-oxygenation-level-dependent (BOLD) MRI signal recorded during a similar FiO2 protocol. A linear relationship with high correlation coefficient between the relative changes in the BOLD MRI signal and the NIRS signal is observed.

Administration, Inhalation↗
PubMed2003

Structural plasticity of the Flp-Holliday junction complex.

The Flp recombinase, a member of the lambda integrase or tyrosine-based family of site-specific recombinases, is an interesting example of an enzyme whose catalytic activity is regulated by protein-protein contacts. It exhibits half-of-the-sites activity throughout its catalytic cycle. Flp is unique among these recombinases, in that it assembles each active site in trans through the interaction of two protein monomers within the catalytic tetramer, with isomerization of interacting pairs being essential to complete a full reaction. We report here the structure of a DNA-bound tetramer of Flpe, a variant of Flp that is more active at 37 degrees C than the wild-type recombinase. This new structure includes the first observation of a tyrosine recombinase with an invading 5'-OH poised to attack the covalent phosphotyrosine residue. Comparison with the previously determined Flp structure highlights differences in flexibility between the two types of protein-protein interfaces in the tetramer and better defines the range of conformations available to this remarkably flexible complex. These results suggest a steric occlusion model for enforcement of half-of-the-sites activity.

Bacterial Outer Membrane Proteins↗
PubMed2003

New insight into site-specific recombination from Flp recombinase-DNA structures.

The lamba integrase, or tyrosine-based family of site-specific recombinases, plays an important role in a variety of biological processes by inserting, excising, and inverting DNA segments. Flp, encoded by the yeast 2-mum plasmid, is the best-characterized eukaryotic member of this family and is responsible for maintaining the copy number of this plasmid. Over the past several years, structural and biochemical studies have shed light on the details of a common catalytic scheme utilized by these enzymes with interesting variations under different biological contexts. The emergence of new Flp structures and solution data provides insights not only into its unique mechanism of active site assembly and activity regulation but also into the specific contributions of certain protein residues to catalysis.

Binding Sites↗
PubMed2003

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1-DNA adducts and p53 mutation in hepatocellular carcinoma.

O(6)-methylguanine-DNA methyltransferase (MGMT) is a repair protein that specifically removes promutagenic alkyl groups from the O(6) position of guanine in DNA. MGMT is transcriptionally silenced by promoter hypermethylation in several human cancers. Methylation-specific PCR (MSP) was used to analyze the MGMT promoter methylation status of 83 hepatocellular carcinomas (HCC) and 2 HCC cell lines (HepG2 and Hep3B). Hypermethylation was detected in 32 of 83 (39%) HCC tissues, but it was not found in either HCC cell line. We also analyzed MGMT expression by immunohistochemical analysis of HCC tissue samples. The presence of aberrant hypermethylation was associated with loss of MGMT protein. The relationship between methylation status and risk factors and tumor markers including environmental exposure to aflatoxin B(1) (AFB(1)), measured as DNA adducts, and status of tumor suppressor gene p53 was also investigated. A statistically significant association was found between MGMT promoter hypermethylation and high level of AFB(1)-DNA adducts in tumor tissues (OR = 5.05, 95% CI = 1.29-19.73). A significant association was also found between methylation and p53 mutation status (OR = 2.97, 95% CI = 1.09-8.11). These results suggest that epigenetic inactivation of MGMT plays an important role in the development of HCC and exposure to environmental carcinogens may be related to altered methylation of genes involved in cancer development. The role of chemical carcinogens in hypermethylation needs further investigation.

Aflatoxin B1↗