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Biomedical subjects

Jun Zhang

Publications and source records attributed to Jun Zhang.

At least 397 records · Page 22Linked to original sources

Detection of outbreaks from time series data using wavelet transform.

In this paper, we developed a new approach to detection of disease outbreaks based on wavelet transform. It is capable of dealing with two problems found in real-world time series data, namely, negative singularity and long-term trends, which may degrade the performance of current approaches to outbreak detection. To test this approach, we introduced artificail disease outbreaks and negative singularities into a real world dataset and applied it and two other algorithms-autoregressive (AR) and Multi-resolution Wavelet Auto-regressive (MWAR) - to this dataset. We compared the performance of these algorithms in terms of sensitivity, specificity and timeliness. The results showed that our approach had similar sensitivity and specificity and slightly better timeliness compared to the other two algorithms. When we introduced negative singularities, its performance did not degrade as much as the other two algorithms' performance. We conclude that our approach to detection, when compared to traditional approaches, may not be as susceptible to degradation of performance caused by negative singularities.

Algorithms↗

[Serological characteristics of a hepatitis E outbreak].

OBJECTIVE: To look into the serological characteristics of a hepatitis E outbreak. METHODS: Sera from the first five patients with acute icteric hepatitis who developed the disease successively within ten days and the 1,675 employees routinely having their lunch in a dining hall of a department (outbreak population) were examined for anti.HEV IgM and IgG at 26th days after the outbreak, and the 883 employees of a neighboring department not having their lunch in the hall were selected as control (control population). RESULTS: The five patients were all positive for anti-HEV IgM and IgG. The positive rates of anti-HEV IgM and IgG in outbreak population were 8.7% and 38.4% respectively, both significantly higher than those in control population which were only 0.1% and 28.6%. The numbers with abnormal ALT in the 145 individuals with anti-HEV IgM(+) of outbreak population were significantly higher than those in the IgM(-) individuals of the same group as well as in control, while the abnormal ALT ratio in the IgM(-) individuals of the outbreak was not higher than that in control. The results from the four patients' serial sera showed that the anti-HEV IgM titers declined gradually and were undetectable at about 4th month after infection, and the IgG titers increased to peak in about 2-3 months after infection, then declined very slowly. The mean IgG titer of the anti-HEV IgM(+) individuals was significantly higher than that of the IgM(-) but IgG(+) individuals in outbreak population, and the latter was significantly higher than the IgG(+) individuals in control, which suggested that the post-infection individuals' immunities to HEV were boosted during the outbreak. There was no difference between sex or age groups for the anti-HEV IgM(+) ratio, but the abnormal ALT was much more frequent in the anti-HEV IgM(+) male than in the female, and no difference was observed between age groups. CONCLUSION: The pathogen of the outbreak of acute icteric hepatitis was hepatitis E virus and associated with food intake. Anti-HEV IgM and IgG were used not only for diagnosis of hepatitis E but also for surveilance in mass population. The attack risk was not associated with age or sex, but the abnormal ALT was much more frequent fresh infectors in male.

Adult↗

[Comparative study of dissolved matter of glycyrrhizic acid before and after supermicro-pulverization of Radix Glycyrrhizae].

OBJECTIVE: To investigate various activities of dissolved matter of glycyrrhizic acid of Radix Glycyrrhizae and the powder by supermicro-pulverization. METHOD: The contents of glycyrrhizic acid in different samples were tested. RESULT: The dissolved matter of glycyrrhizic acid was greatly increased by supermicro-pulverization. The more time used for grinding, the smaller the size of the powder, and the easier the glycyrrhizic acid would be dissolved. CONCLUSION: Supermicro-pulverization is helpful to the dissolved matter of glycyrrhizic acid of Radix Glycyrrhizae, and the size of powder exerts great influence on dissolved matter of glycyrrhizic acid.

Drug Combinations↗

[The construction of yak liver cDNA library].

Yak is a very useful animal. The cDNA library of yak liver was constructed, which made a preparation for further cloning and expressing of wanted genes.mRNA from yak liver was extracted and purified, and cDNA was obtained by reverse transcription,and then cDNA library was constructed using plasmid pSPORT1 as the vector. The volume of the library was 1 x 10(6) transformants/microg cDNA and the rate of recombination was 93%. The results indicated that the cDNA library had enough volume for selecting wanted genes and made the basic of studying yak's genetic background.

English Abstract↗

[Orange fluorescent protein--modification of green fluorescent protein GFPxm].

Recently, we have reported a new gfp gene isolated from Aequorea macrodactyla. The protein purified from expressed E. coli exhibited an excitation peak at 476 nm and an emission peak at 496 nm. However, the drawback of only maturing to fluorescence at low temperature limited its applications. In this paper, we further describe twelve mutants of GFPxm. Seven mutants produced enhanced fluorescence when expressed in E. coli at higher temperature (37 degrees C). After six hours of induction at 25 degrees C, 32 degrees C and 37 degrees C respectively, the relative fluorescent intensities of GFPxm16, GFPxm18 and GFPxm19 were higher than that of EGFP, moreover GFPxm16 and GFPxm163 could preserve high fluorescent intensity even expressed at 42 degrees C. Four mutants of the seven could reach high expression level in three kind of mammalian cells. Another 6 mutants had red-shift of excitation-emission maxima, and longest excitation-emission maxima were 514nm and 525nm. Another three mutants had two excitation peaks, and one mutant had only one UV-excitation peak. The most exciting result is the mutant of OFPxm with orange color. The mutant has an excitation peak at 509 nm and an emission peak at 523nm. 523nm is yellowish green but the protein is orange observed by eyes. The mutant could reach high expression level and matured at higher temperature but the fluorescent intensity was comparatively low because of low quantum yield.

Animals↗

[Rapid and efficient expression of foreign genes in mammalian cells by baculovirus vectors].

The baculovirus insect cell expression system has been used extensively for the expression of recombinant proteins in insect cells. Recently, reports have described that recombinant baculoviruses can transduce a broad spectrum of primary and established mammalian cells, which shows the baculoviruses could serve as a new gene-transfer vehicle for mammalian cells. In this report, we further research the modification of baculovirus vector and the way to deliver exogenous gene into mammalian cells. On the base of Bac-to-Bac baculovirus insect cell expression system, two recombinant baculoviruses (BacV-CMV-EGFPA, BacV-CMV-EGFPB) were constructed containing different direction of CMV promoters which controll the expression of a reporter gene (EGFP). We found that CMV promoter could direct expression of reporter gene in Sf9 cells with relatively low efficiency. The culture supernatant of Sf9 cells which have been infected by the recombinant baculoviruses for four days were collected and the titers of the viruses in culture supernatant were determined by plaque assay on Sf9 cells. The HepG2 cells, an human hepatocellular carcinoma cell line, were directly incubated with the collected culture supernatant which contains the recombinant baculoviruses for 8 hours in 37 degrees C CO2 incubator (moi = 100). Twenty-four hours post transduction the efficiencies of gene-transfer and expression were analyzed by flow cytometry (FCM) which detect the green fluorescence of individual cells. Results show that these two recombinant baculoviruses have similar gene-transfer and expression efficiency in HepG2 cells, which means the direction of CMV promoters has no effects on reporter gene expression. The optimal transduction conditions of incubating the mammalian cells with the culture supernatant of Sf9 cells infected by recombinant baculoviruses for four days were determined by FCM assay in HepG2 cells. The HepG2 cells inoculated in 24-well plate (5 x 10(4)/well) were incubated with the culture supernatant (BacV-CMV-EGFPA, 1.2 x 10(7) pfu/mL) serially diluted by DMEM culture medium containing 10% FBS and the transduction times ranged from 1 to 24 hours. Twenty-four hours post transduction the efficiencies of gene-transfer and expression were analyzed by FCM. Results show that incubating the target cells with the 1:1 diluted culture supernatant (moi = 50) for 12 hours in 37 degrees C CO2 incubator would achieve the highest infection and expression efficiency with the least impairment on cell viability. We compared the gene-transfer and expression efficiency of recombinant baculovirus in HepG2 and CV1 cells with lipofectAMINE and recombinant retrovirus system, results show that under the similar conditions the recombinant baculovirus could achieve the highest gene-transfer and expression efficiency than the other two systems. So we can draw a conclusion that directly incubating the mammalian cells with the culture supernantant of the infected Sf9 cells could serve as a very convenient way for rapid and efficient expression of foreign gene in mammalian cells.

Animals↗

[Selection of a peptide mimic the neutralization epitope of hepatitis E virus with phage peptide display technology].

Hepatitis E is an acute hepatitis casused by hepatitis E virus (HEV) in developing countries, where it occurs as cases sporadic and in epidemics form. The causative agent, hepatitis E virus, is transmitted primarily by the fecal-oral route. HEV is icosahedron non-enveloped virus, and its genome is a single-stranded, positive-sense, 3'-polyadenylated RNA about 7.5 kb in length. It contains three open reading frames (ORFs). Of which ORF1 codes for a polyprotein of 1693 amino acids and contain domains homologous to a viral methyltransferase, a papainlike cysteine protease, an RNA helicasre, and an RNA-dependent RNA polymerase, besides the most hypervariable region of the HEV genome. And ORF3 codes for a 123-amino-acide-long polypeptide with unknown function. While the major viral capsid protein (pORF2, ORF2 codes) of 660 amino acid was showed to contain the protective epitope. The bacterially expressed polypeptide disignated as NE2 has been proved to be a protective antige. And the anti-NE2 monoclonal antibodies (mAb) was screend, two of these mAbs 8C11 and 8H3 were showed to be against separate conformational neutralization epitope of hepatitis E virus (HEV). And these two mAb were used to screen for binding peptides from a 7-peptides phage display library. After four rounds of panning, tweenty-one positive monoclonal phages (11 for 8C11, and 10 for 8H3) were selected and the inserted fragments were sequenced. The DNA sequence coding for the obtained dominant peptide 8C11 (N'-His-Pro-Thr-Leu-Leu-Arg-Ile-C', named 8C11A) and 8H3 (N'-Ser-Ile-Leu-Pro-Tyr-Pro-Tyr-C', named 8H3A) were then synthesized and cloned to insert between amino acid 78 to 83 of hepatitis B core antigen (HBcAg), then expressed in E. coli. The recombinant proteins aggregate into homodimer or polymer on SDS-PAGE, and could bind with mAb 8C11 and 8H3 in Western blotting. Respectively, the recombinant protein C8C11A showed to be dimer mainly, which can bind with mAb 8C11. The monomer and dimer of C8H3A are in the same amount on SDS-PAGE, but only the dimer could bind with mAb 8H3 on Western blotting. The renatured recombinant proteins were all showed to aggregate into virus like particles which were similar as HBcAg on transmission electron micrograph. The dominant peptide 8H3A (N'-Ser-Ile-Leu-Pro-Tyr-ProTyr-C') that selected out by mAb 8H3 was further chemo-synthesized, and its binding activity was confirmed by BIAcore biosensor. The result showed that this 7-peptide can bind with mAb 8H3 in a big Ka and Kd form, which means the binding is not stable. These results implicated that conformational dependent neutralization epitope could be partially modeled by short peptide, which provided a feasible route for subunit vaccine development.

Amino Acid Sequence↗

[The immuno-protect study of a hepatitis E virus ORF2 peptide expressed in E. coli].

A hepatitis E virus (HEV) ORF2 peptide expressed in an unfused pattern in E. coli, NE2, can self-assembly into homodimers and oligomers, and the immuno-reactivity of the dimers or oligomers to HEV infected serum is much stronger than monomer, which suggested that some important conformational epitopes be better exposed in dimer or oligomer form. Three Rhesus monkeys were vaccinated with three doses (10 microg/dose) purified NE2 in Freud's adjuvant under a schedule of Od, 10d, and 30d. Specific antibodies can be detected on second week, and on sixth week while virus challenge were performed with 106 PCR titer of virus positive stool suspention, the antibody titer of one monkey was 1: 100 000, the other two were both 1: 20 000. Three monkeys in control group presented typical acute hepatitis E manifestation: increased seral amino transferase (ALT), antibody conversion, and continuous virus excretion in stool. In contrast, the ALT of monkeys in vaccinated group continued to be normal, stool virus had not been detected in one monkey, and presented only a short duration in another two. One NE2-vaccinated monkey serum with antibody titer 1: 20 000 was first incubated with HEV (10(3) PCR titer) for neutralization, then the mixture were used to challenge two monkeys, the results showed that two monkeys in control group continued to excrete virus for more than three weeks, sera antibody conversion, and one monkey presented obvious ALT increase. Both two monkeys challenged with antibody neutralized virus had not detected virus in stool, the antibodies decreased slowly, and ALT continued to be normal. These results suggested that the prokaryotic expression recombinant protein NE2 have good immunogenicity and immunoprotectivity, and should be a good candidate for an effective hepatitis E vaccine.

Alanine Transaminase↗

Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice.

Thyrotropin-releasing hormone (TRH) and some of its stable analogues have been shown to improve neurologic dysfunctions such as brain trauma in both animals and humans. Our previous study revealed that taltirelin, a novel orally active TRH analogue, binds to rat brain TRH receptors in vivo. The present study was undertaken to investigate whether taltirelin has neuroprotective effects in transient brain ischemia of C57BL/6J mice induced by bilateral carotid artery occlusion (2VO). Neuronal cell density in the hippocampal CA1 region of C57BL/6J mice was significantly (39.9%) decreased 1 week after 2VO-reperfusion, compared to the case of the sham group, and this reduction of hippocampal neuronal density was significantly suppressed by an intravenous (i.v.) injection of taltirelin (0.3 mg/kg). The i.v. injection of taltirelin at this dosage produced a significant increase in the dissociation constant (Kd) of specific [3H]MeTRH binding in sham and 2VO-reperfusion groups (33.6 and 51.4%, respectively) compared with the vehicle-treated group. These results indicate that the intravenously injected taltirelin bound to TRH receptors in the ischemic brain. There was little difference in the brain-to-plasma concentration ratio (Kp) of [14C]sucrose between the sham and 2VO groups of C57BL/6J mice, indicating that the tight junction of the blood-brain barrier may be intact in the ischemic brain. In conclusion, the study has shown that taltirelin may have a significant neuroprotective effect on the ischemic brain.

Animals↗

A TNF family member LIGHT transduces costimulatory signals into human T cells.

DcR3/TR6 is a secreted protein belonging to the TNFR family. It binds to Fas ligand, LIGHT, and TL1A, all of which are TNF family members. LIGHT is expressed on activated T cells. Its known receptors are TR2 and LTbetaR on the cell surface, and TR6 in solution. In the present study, we report soluble TR6-Fc or solid-phase TR6-Fc costimulated proliferation, lymphokine production, and cytotoxicity of human T cells in the presence of TCR ligation. These costimulating effects were blocked by soluble LIGHT but not by soluble Fas-Fc. TR6-Fc could also effectively costimulate gld/gld mouse T cells. We further demonstrated that TR6 bound to both Th1 and Th2 cells, according to flow cytometry, and that the association was inhibited by soluble LIGHT. Cross-linking Th1 and Th2 cells with solid-phase TR6-Fc along with a suboptimal concentration of anti-CD3 enhanced proliferation of both Th1 and Th2 cells, and augmented Th1 but not Th2 lymphokine production. These data suggest that TR6 delivers costimulation through its ligand(s) on the T cell surface, and at least the major part of such costimulation is via LIGHT.

Adjuvants, Immunologic↗

[Gleason scores of prostate needle biopsy specimens and of radical prostatectomy specimens, a comparative study].

OBJECTIVE: To compare the Gleason scores of the prostate needle biopsy specimens with those of the radical prostatectomy specimens. METHODS: Gleason scoring was made on the needle biopsy specimens from 40 patients with prostate carcinoma and then on the radical prostatectomy specimens from the same patients. The Gleason scores of the two sets of matched specimens were compared. RESULTS: The Gleason scores were 2 approximately 9 (5.6 +/- 1.7) of the prostate needle biopsy specimens, significantly different from those of the radical prostatectomy specimens [4 approximately 10 (6.4 +/- 1.3), P < 0.05]. The Gleason scores coincided in 23 cases (57.5%) between the two groups. The Gleason scores of 15 needle biopsy specimens were significantly lower than those of the matched radical prostatectomy specimens with an underestimation rate of 37.5% and were higher in 2 needle biopsy specimens than in the matched radical prostatectomy specimens with an overestimation rate of 5.0%. The number of cases with the Gleason score < or = 6 in the needle biopsy group were 25, significantly less than that in the radical prostatectomy group (P < 0.01). The number of cases with the Gleason score > or = 7 in the needle biopsy group was 15, not significantly different from that in the prostatectomy group (P = 0.07). CONCLUSION: Prostate needle biopsy under-grades the Gleason scores in comparison with radical prostatectomy. Measures should be adopted to avoid underestimation of the tumor grade.

Aged↗

Drag reduction through self-similar bending of a flexible body.

The classical theory of high-speed flow predicts that a moving rigid object experiences a drag proportional to the square of its speed. However, this reasoning does not apply if the object in the flow is flexible, because its shape then becomes a function of its speed--for example, the rolling up of broad tree leaves in a stiff wind. The reconfiguration of bodies by fluid forces is common in nature, and can result in a substantial drag reduction that is beneficial for many organisms. Experimental studies of such flow-structure interactions generally lack a theoretical interpretation that unifies the body and flow mechanics. Here we use a flexible fibre immersed in a flowing soap film to measure the drag reduction that arises from bending of the fibre by the flow. Using a model that couples hydrodynamics to bending, we predict a reduced drag growth compared to the classical theory. The fibre undergoes a bending transition, producing shapes that are self-similar; for such configurations, the drag scales with the length of self-similarity, rather than the fibre profile width. These predictions are supported by our experimental data.

Journal Article↗

Mouse T cells receive costimulatory signals from LIGHT, a TNF family member.

LIGHT is a tumor necrosis factor (TNF) family member and is expressed on activated T cells. Its known receptors are TR2 and LTbetaR on the cell surface, and TR6/DcR3 in solution. TR6/DcR3 is a secreted protein belonging to the TNF receptor family. It binds to Fas ligand (FasL), LIGHT, and TL1A, all of which are TNF family members. In the present study, we report that solid-phase TR6-Fc costimulated proliferation, lymphokine production, and cytotoxicity of mouse T cells upon T-cell receptor (TCR) ligation. A monoclonal antibody against LIGHT similarly costimulated mouse T cells in their proliferation response to TCR ligation. These data suggest LIGHT, although a ligand, can receive costimulation when expressed on the T-cell surface. Mechanistically, when T cells were activated by TCR and CD28 co-cross-linking, TCR and rafts rapidly formed caps where they colocalized. LIGHT rapidly congregated and colocalized with the aggregated rafts. This provided a molecular base for the signaling machinery of LIGHT to interact with that of TCR. Indeed, LIGHT cross-linking enhanced p44/42 mitogen-activated protein kinase activation after TCR ligation. This study reveals a new function and signaling event of LIGHT.

Animals↗

Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR.

We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity. Known CAR activators as well as high doses of acetaminophen induced expression of three acetaminophen-metabolizing enzymes in wild-type but not in CAR null mice, and the CAR null mice were resistant to acetaminophen toxicity. Inhibition of CAR activity by administration of the inverse agonist ligand androstanol 1 hour after acetaminophen treatment blocked hepatotoxicity in wild type but not in CAR null mice. These results suggest an innovative therapeutic approach for treating the adverse effects of acetaminophen and potentially other hepatotoxic agents.

Acetaminophen↗

Characteristics of self-guided laser plasma channels generated by femtosecond laser pulses in air.

With ultrashort laser pulses (25 fs) and low energy (E=15 mJ), we observe laser plasma channels with a length over 5 m in air. The diameter of the plasma channel is measured to be 120 microm. The average electron density in the channel is inferred to be about 10(18) W/cm(3) with an interferometric method. At the same time, the temporal evolution of the electron density in the plasma channel is investigated. The resistivity in the plasma channel is measured to be less than 1 Omega cm. It is suggested that the lifetime of the plasma channel can be greatly prolonged by launching another long laser pulse along the plasma channel.

Journal Article↗

A novel transactivating factor that regulates interferon-gamma-dependent gene expression.

We have previously identified a novel interferon (IFN)-stimulated cis-acting enhancer element, gamma-IFN-activated transcriptional element (GATE). GATE differs from the known IFN-stimulated elements in its primary sequence. Preliminary analysis has indicated that the GATE-dependent transcriptional response requires the binding of novel transacting factors. A cDNA expression library derived from an IFN-gamma-stimulated murine macrophage cell line was screened with a (32)P-labeled GATE probe to identify the potential GATE-binding factors. A cDNA coding for a novel transcription-activating factor was identified. Based on its discovery, we named it as GATE-binding factor-1 (GBF-1). GBF-1 homologs are present in mouse, human, monkey, and Drosophila. It activates transcription from reporter genes carrying GATE. It possesses a strong transactivating activity but has a weak DNA binding property. GBF-1 is expressed in most tissues with relatively higher steady-state levels in heart, liver, kidney, and brain. Its expression is induced by IFN-gamma treatment. GBF-1 is present in both cytosolic and nuclear compartments. These studies thus identify a novel transactivating factor in IFN signaling pathways.

Amino Acid Sequence↗