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Fei Wang

Publications and source records attributed to Fei Wang.

At least 91 records · Page 5Linked to original sources
PubMed2004

A highly sensitive assay for spectrofluorimetric determination of reduced glutathione using organic nano-probes.

In this study, the new nanometer-sized fluorescent particles (1-pyrenemethylamine nanoparticles) have been prepared by reprecipitation method under ultrasonic radiation. These nanoparticles have the potential to overcome problems encountered by organic small molecules by combining the advantages of high photobleaching threshold, high quantum yield, long fluorescence lifetime, good chemical stability, and wide excitation spectral properties. These nanoparticles will be able to be directly used as fluorescent nanoparticles probe without modification. A new fluorimetric method for the determination of reduced glutathione (GSH) has been developed with these nanoparticles. Under optimal conditions, the organic nanoparticles reacted with GSH and o-phthalaldehyde (OPA) to give a highly fluorescent derivative in Na2CO3-HCl buffer (pH=9.0). The fluorescence excitation and emission wavelengths of fluorescent derivative were located at 345 and 400 nm, respectively. The relative fluorescence intensity (RF) was linear in the range of the GSH concentration from 8.0x10(-7) to 1.1x10(-4)moll(-1). Limit of detection of 7.1x10(-8)moll(-1) was achieved for the reduced glutathione. The method was validated and applied to the analysis of three synthetic samples containing reduced glutathione.

Calibration↗
PubMed2004

Calpain and other cytosolic proteases can contribute to the degradation of retro-translocated prion protein in the cytosol.

PrP, a cell surface-localized N-linked glycoprotein, is required for the pathogenesis of prion diseases. Recent studies have revealed that prion protein (PrP) becomes neurotoxic and prone to aggregation when it is in the cytosol, suggesting that cytosolic PrP may play a role in the pathogenesis of prion disease. Retro-translocation of PrP from the endoplasmic reticulum to the cytosol for proteasome degradation offers a natural route for PrP to enter the cytosol, but whether PrP is subject to retrotranslocation is controversial. In this study, we investigated the metabolism of endogenous wild-type PrP in several cell lines and in primary mouse cortical neurons. Our results suggest that a portion of the endogenous wild-type PrP is retro-translocated to the cytosol and degraded by the proteasome. Moreover, we also found that calpain and other cytosolic proteases could degrade PrP in the cytosol when the proteasome activity is compromised. These results provide the foundation for the hypothesis that cytosolic PrP may be involved in the pathogenesis of prion disease.

Animals↗
PubMed2004

Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing.

Inhalation of nitric oxide (NO) improved arterial oxygenation and enabled the reduction of inspired oxygen therapy and airway pressure support in patients with severe acute respiratory syndrome (SARS). In addition, chest radiography showed decreased spread or density of lung infiltrates, and the physiological effects remained after termination of inhaled NO therapy. These findings suggest not only a pulmonary vasodilator effect of inhaled NO, but also an effect on SARS.

Administration, Inhalation↗
PubMed2004

Targeting virological core groups: a new paradigm for controlling herpes simplex virus type 2 epidemics.

BACKGROUND: Classic modeling of sexually transmitted diseases has focused on modeling behavioral heterogeneity and designing epidemic control strategies targeted at behavioral core groups. METHODS: We analyzed a new mathematical model of herpes simplex virus type 2 (HSV-2) epidemics that includes virological core groups (i.e., groups of individuals with high rates of viral reactivation) and suggest a new paradigm for epidemic control. We used our model, in conjunction with virological data, to determine the potential role of virological core groups in contributing to transmission and the effect that daily antiviral therapy (DAT) could have on reducing transmission if virological core groups were targeted. RESULTS: We estimated that a virological core group (11% of infected individuals) can cause a disproportionately large percentage (44%) of new infections and that a median of only 6.4 person-years of DAT would be necessary to prevent 1 HSV-2 infection. We determined that relatively few individuals would need to receive DAT to substantially reduce the incidence of HSV-2 infection. CONCLUSION: Identifying and targeting individuals in the virological core group could be an effective and practical public health strategy for reducing transmission. Treating individuals who are high-frequency viral shedders should be evaluated as a strategy for reducing HSV-2 transmission.

Antiviral Agents↗
PubMed2004

A mathematical treatment of integrated Ca dynamics within the ventricular myocyte.

We have developed a detailed mathematical model for Ca2+ handling and ionic currents in the rabbit ventricular myocyte. The objective was to develop a model that: 1), accurately reflects Ca-dependent Ca release; 2), uses realistic parameters, particularly those that concern Ca transport from the cytosol; 3), comes to steady state; 4), simulates basic excitation-contraction coupling phenomena; and 5), runs on a normal desktop computer. The model includes the following novel features: 1), the addition of a subsarcolemmal compartment to the other two commonly formulated cytosolic compartments (junctional and bulk) because ion channels in the membrane sense ion concentrations that differ from bulk; 2), the use of realistic cytosolic Ca buffering parameters; 3), a reversible sarcoplasmic reticulum (SR) Ca pump; 4), a scheme for Na-Ca exchange transport that is [Na]i dependent and allosterically regulated by [Ca]i; and 5), a practical model of SR Ca release including both inactivation/adaptation and SR Ca load dependence. The data describe normal electrical activity and Ca handling characteristics of the cardiac myocyte and the SR Ca load dependence of these processes. The model includes a realistic balance of Ca removal mechanisms (e.g., SR Ca pump versus Na-Ca exchange), and the phenomena of rest decay and frequency-dependent inotropy. A particular emphasis is placed upon reproducing the nonlinear dependence of gain and fractional SR Ca release upon SR Ca load. We conclude that this model is more robust than many previously existing models and reproduces many experimental results using parameters based largely on experimental measurements in myocytes.

Action Potentials↗
PubMed2004

Positive association of the human frizzled 3 (FZD3) gene haplotype with schizophrenia in Chinese Han population.

Frizzled 3 (FZD3) gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. The FZD3 is a transmembrane receptor required for Wnt signal transduction cascades that have been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Previous work has showed a strong association between FZD3 locus and schizophrenia in family-based study. To confirm this issue further, we investigated a genetic association between four single nucleotide polymorphisms (SNPs) located in the FZD3 gene and schizophrenia by case-control study using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) in the Chinese Han population. Our studies showed the SNPs rs2323019 and rs880481 have significant differences in both genotype and allele frequencies between control subjects and schizophrenic patients (rs2323019: Allele A > G, chi2 = 6.7277, df = 1, P = 0.0095; Genotype, chi2 = 10.6583, df = 2, P = 0.0049; rs880481: Allele A > G, chi2 = 10.3945, df = 1, P = 0.0013; Genotype, chi2 = 16.8049, df = 2, P = 0.0002). In addition, we constructed three-locus haplotypes to test their association with schizophrenia. The globe chi-squared test for haplotype analysis showed a significant association (chi2 = 66.38, df = 7, P < 0.000001). These results suggested that the FZD3 gene might be involved in the predisposition to schizophrenia.

Adult↗
PubMed2004

The F-box protein AhSLF-S2 controls the pollen function of S-RNase-based self-incompatibility.

Recently, we have provided evidence that the polymorphic self-incompatibility (S) locus-encoded F-box (SLF) protein AhSLF-S(2) plays a role in mediating a selective S-RNase destruction during the self-incompatible response in Antirrhinum hispanicum. To investigate its role further, we first transformed a transformation-competent artificial chromosome clone (TAC26) containing both AhSLF-S(2) and AhS(2)-RNase into a self-incompatible (SI) line of Petunia hybrida. Molecular analyses showed that both genes are correctly expressed in pollen and pistil in four independent transgenic lines of petunia. Pollination tests indicated that all four lines became self-compatible because of the specific loss of the pollen function of SI. This alteration was transmitted stably into the T1 progeny. We then transformed AhSLF-S(2) cDNA under the control of a tomato (Lycopersicon esculentum) pollen-specific promoter LAT52 into the self-incompatible petunia line. Molecular studies revealed that AhSLF-S(2) is specifically expressed in pollen of five independent transgenic plants. Pollination tests showed that they also had lost the pollen function of SI. Importantly, expression of endogenous SLF or SLF-like genes was not altered in these transgenic plants. These results phenocopy a well-known phenomenon called competitive interaction whereby the presence of two different pollen S alleles within pollen leads to the breakdown of the pollen function of SI in several solanaceaous species. Furthermore, we demonstrated that AhSLF-S(2) physically interacts with PhS(3)-RNase from the P. hybrida line used for transformation. Together with the recent demonstration of PiSLF as the pollen determinant in P. inflata, these results provide direct evidence that the polymorphic SLF including AhSLF-S(2) controls the pollen function of S-RNase-based self-incompatibility.

Amino Acid Sequence↗
PubMed2004

Alternative splicing of the APC gene in the neural retina and retinal pigment epithelium.

PURPOSE: Hypertrophy and hyperplasia of the retinal pigment epithelium (RPE) is associated with an inherited predisposition to human familial adenomatous polyposis coli, suggesting that expression of the adenomatous polyposis coli (APC) tumor suppressor may regulate RPE proliferation/differentiation. Distinctive APC isoforms exist in different cell types due to alternative splicing of the APC transcripts. We hypothesize that differences in expression patterns of APC protein isoforms are critical to RPE proliferation/differentiation. METHODS: To investigate these relationships, APC gene expression was characterized in the retinas and RPE from fetal and adult human and mouse, and in the epiretinal membranes (ERM) from 5 patients with proliferative vitreoretinopathy (PVR). Expression patterns of alternative splice-forms of APC transcripts were evaluated by comparative quantitative RT-PCR. Exon 1 of APC encodes a heptad repeat that confers the ability of APC to homodimerize. APC protein isoforms containing or lacking this heptad were characterized by western blot analysis and immunohistochemistry. RESULTS: Comparative quantitative RT-PCR demonstrated a predominant exon 1 containing, conventional APC splice-form in the early developing fetal RPE and retina, and in all the tested ERM samples from patients with PVR. This method also demonstrated an increased level of exon 1 lacking APC splice-form in the mature RPE and retina. Western blot analysis and immunofluorescence microscopy demonstrated the conventional APC only in the RPE, and the APC isoform without the first heptad repeat in both the retina and RPE. Immunofluorescence microscopy also demonstrated only the conventional APC in the ERM samples tested. CONCLUSIONS: These results suggest that alternative splicing of APC leads to differential APC expression with potentially unique functions. APC isoform without the first heptad repeat may play a role in cell cycle cessation in the adult retina and RPE, and the down regulation of this APC isoform may contribute to the potential of RPE to migrate and proliferate.

Adenomatous Polyposis Coli Protein↗
PubMed2004

Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed.

BACKGROUND: Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors. The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model. METHODS: Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice. Vaccination with anthrax protective antigen and lethal factor produced a significant increase in antigen specific human IgG in the mouse serum. The antibody producing lymphocytes were immortalized by hybridoma formation. The genes encoding the protective antibodies were rescued and stable cell lines expressing full-length human immunoglobulin were established. The antibodies were characterized by; (1) surface plasmon resonance; (2) inhibition of toxin in an in vitro mouse macrophage cell line protection assay and (3) in vivo in a Fischer 344 bolus lethal toxin challenge model. RESULTS: The range of antibodies generated were diverse with evidence of extensive hyper mutation, and all were of very high affinity for PA83~1 x 10-10-11M. Moreover all the antibodies were potent inhibitors of anthrax lethal toxin in vitro. A single IV dose of AVP-21D9 or AVP-22G12 was found to confer full protection with as little as 0.5x (AVP-21D9) and 1x (AVP-22G12) molar equivalence relative to the anthrax toxin in the rat challenge prophylaxis model. CONCLUSION: Here we describe a powerful technology to capture the recall antibody response to AVA vaccination and provide detailed molecular characterization of the protective human monoclonal antibodies. AVP-21D9, AVP-22G12 and AVP-1C6 protect rats from anthrax lethal toxin at low dose. Aglycosylated versions of the most potent antibodies are also protective in vivo, suggesting that lethal toxin neutralization is not Fc effector mediated. The protective effect of AVP-21D9 persists for at least one week in rats. These potent fully human anti-PA toxin-neutralizing antibodies are attractive candidates for prophylaxis and/or treatment against Anthrax Class A bioterrorism toxins.

Journal Article↗
PubMed2004

atToc159 is a selective transit peptide receptor for the import of nucleus-encoded chloroplast proteins.

The members of the Toc159 family of GTPases act as the primary receptors for the import of nucleus-encoded preproteins into plastids. Toc159, the most abundant member of this family in chloroplasts, is required for chloroplast biogenesis (Bauer, J., K. Chen, A. Hiltbunner, E. Wehrli, M. Eugster, D. Schnell, and F. Kessler. 2000. Nature. 403:203-207) and has been shown to covalently cross-link to bound preproteins at the chloroplast surface (Ma, Y., A. Kouranov, S. LaSala, and D.J. Schnell. 1996. J. Cell Biol. 134:1-13; Perry, S.E., and K. Keegstra. 1994. Plant Cell. 6:93-105). These reports led to the hypothesis that Toc159 functions as a selective import receptor for preproteins that are required for chloroplast development. In this report, we provide evidence that Toc159 is required for the import of several highly expressed photosynthetic preproteins in vivo. Furthermore, we demonstrate that the cytoplasmic and recombinant forms of soluble Toc159 bind directly and selectively to the transit peptides of these representative photosynthetic preproteins, but not representative constitutively expressed plastid preproteins. These data support the function of Toc159 as a selective import receptor for the targeting of a set of preproteins required for chloroplast biogenesis.

Arabidopsis↗
PubMed2004

Specificity of a soluble UDP-galactose: fucoside alpha1,3-galactosyltransferase that modifies the cytoplasmic glycoprotein Skp1 in Dictyostelium.

Skp1 is an adaptor-like protein in E3(SCF)-ubiquitin ligases and other multiprotein complexes of the cytoplasm and nucleus. In Dictyostelium, Skp1 is modified by an unusual pentasaccharide containing a Galalpha1-Fuc linkage, whose formation is examined here. A cytosolic extract from Dictyostelium was found to yield, after 2400-fold purification, an activity that could transfer Gal from UDP-Gal to both a Fuc-terminated glycoform of Skp1 and synthetic Fuc conjugates in the presence of Mn(2+) and dithiothreitol. The microsomal fraction was devoid of activity. The linkage formed was Galalpha1,3Fuc based on co-chromatography with only this synthetic isomer conjugate, and sensitivity to alpha1,3/6-galactosidase. Skp1 exhibited an almost 1000-fold lower K(m) and 35-fold higher V(max) compared with a simple alpha-fucoside, but this advantage was abolished by denaturation or alkylation of Cys residues. A comparison of a complete series of synthetic glycosides representing the non-reducing terminal mono-, di-, and trisaccharides of Skp1 revealed, surprisingly, that the disaccharide is most active owing primarily to a V(max) advantage, but still much less active than Skp1 itself because of a K(m) difference. These findings indicate that alpha-GalT1 is a cytoplasmic enzyme whose modification of Skp1 requires proper presentation of the terminal acceptor disaccharide by a folded Skp1 polypeptide, which correlates with previous evidence that the Galalpha1,3Fuc linkage is deficient in expressed mutant Skp1 proteins.

Animals↗
PubMed2004

Defective expression of transforming growth factor beta receptor type II is associated with CpG methylated promoter in primary non-small cell lung cancer.

PURPOSE: Reduced expression of the transforming growth factor beta receptor type II (TGF beta RII), a key inhibitor of epithelial cell growth and tumor suppressor gene, was reported frequently in many types of tumors including non-small cell lung cancer (NSCLC). This study explored the significance of the TGF beta RII gene in NSCLC carcinogenesis. EXPERIMENTAL DESIGN: With 43 independent pairs of tumor and paracarcinoma tissue samples from patients with primary NSCLC, we carried out PCR-denaturing gradient gel electrophoresis screening for DNA variants over the coding sequence of the TGF beta RII gene, immunohistochemical assay of TGF beta RII expression, methylation-specific PCR analysis, and semiquantitative reverse transcription-PCR. RESULTS: The PCR-denaturing gradient gel electrophoresis did not detect variation in the whole coding sequence of the TGF beta RII gene, but the immunohistochemistry experiment revealed reduced or lost expression of the gene in 44% (19 of 43) of the tumor samples. The methylation analysis on the 19 pairs detected the frequent occurrence of methylated TGF beta RII promoter in tumor tissues, whereas most of the paracarcinoma tissues were free of methylation. The reduced TGF beta RII expression was highly significantly associated with the methylation event (P < 10(-4)). The reverse transcription-PCR analysis demonstrated a clear agreement between reduced TGF beta RII expression and decreased mRNA level of the gene in the tumor tissue samples. CONCLUSIONS: TGF beta RII plays an important role as a tumor suppressor in NSCLC carcinogenesis. The defective expression may serve as one of most important molecular mechanisms in explaining progression of the disease. In particular, aberrant 5' CpG methylation of the gene has explained the down-regulation of the gene at a transcriptional level.

Adult↗
PubMed2004

Polarity and proliferation are controlled by distinct signaling pathways downstream of PI3-kinase in breast epithelial tumor cells.

Loss of tissue polarity and increased proliferation are the characteristic alterations of the breast tumor phenotype. To investigate these processes, we used a three-dimensional (3D) culture system in which malignant human breast cells can be reverted to a normal phenotype by exposure to inhibitors of phosphatidylinositol 3-kinase (PI3K). Using this assay, we find that Akt and Rac1 act as downstream effectors of PI3K and function as control points of cellular proliferation and tissue polarity, respectively. Our results also demonstrate that the PI3K signaling pathway is an integral component of the overall signaling network induced by growth in 3D, as reversion affected by inhibition of PI3K signaling also down-modulates the endogenous levels of beta1 integrin and epidermal growth factor receptor, the upstream modulators of PI3K, and up-regulates PTEN, the antagonist of PI3K. These findings reveal key events of the PI3K pathway that play distinct roles to maintain tissue polarity and that when disrupted are instrumental in the malignant phenotype.

Actins↗
PubMed2004

Efficient heterogeneous asymmetric transfer hydrogenation of ketones using highly recyclable and accessible silica-immobilized Ru-TsDPEN catalysts.

[reaction: see text] Chiral Ru-TsDPEN [N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]-derived catalysts were first successfully immobilized onto amorphous silica gel and mesoporous silicas of MCM-41 and SBA-15 by an easily accessible approach. The catalyst immobilized on silica gel demonstrated remarkably high catalytic activities and excellent enantioselectivities (up to >99% ee) for the heterogeneous asymmetric transfer hydrogenation of various ketones. Particularly, the catalyst could be readily recovered and reused in multiple consecutive catalytic runs (up to 10 uses) with the completely maintained enantioselectivity.

Journal Article↗
PubMed2004

Recruitment of voluntary non-remunerated apheresis donors: the second five years' experience in Shenzhen.

The voluntary non-remunerated blood donation campaign in Shenzhen, China, was launched in 1993 and the smooth change from paid donors to unpaid took only a decade. In the first half the volunteer donation system and a sufficient blood supply was promoted and this paved the way for further development in the second half during which the non-remunerated donation system became substantial and integral due to recruitment for plateletapheresis and peripheral stem cells donation as well as whole blood donations. Ninety percent of the donors registered for plateletapheresis do donate and none of the twenty-three non-related donors with matched HLA genotypes broke their promise to donate their peripheral stem cells.

Altruism↗
PubMed2004

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

OBJECTIVE: To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. DESIGN: Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. SETTING: Models were replicated in 3 populations. PARTICIPANTS: Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Inpatient, outpatient, and total days of care in FY97. RESULTS: The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). CONCLUSIONS: The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

Activities of Daily Living↗
PubMed2004

Genetic and bioinformatic analysis of 41C and the 2R heterochromatin of Drosophila melanogaster: a window on the heterochromatin-euchromatin junction.

Genomic sequences provide powerful new tools in genetic analysis, making it possible to combine classical genetics with genomics to characterize the genes in a particular chromosome region. These approaches have been applied successfully to the euchromatin, but analysis of the heterochromatin has lagged somewhat behind. We describe a combined genetic and bioinformatics approach to the base of the right arm of the Drosophila melanogaster second chromosome, at the boundary between pericentric heterochromatin and euchromatin. We used resources provided by the genome project to derive a physical map of the region, examine gene density, and estimate the number of potential genes. We also carried out a large-scale genetic screen for lethal mutations in the region. We identified new alleles of the known essential genes and also identified mutations in 21 novel loci. Fourteen complementation groups map proximal to the assembled sequence. We used PCR to map the endpoints of several deficiencies and used the same set of deficiencies to order the essential genes, correlating the genetic and physical map. This allowed us to assign two of the complementation groups to particular "computed/curated genes" (CGs), one of which is Nipped-A, which our evidence suggests encodes Drosophila Tra1/TRRAP.

Animals↗