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Biomedical subjects

Jian Zhang

Publications and source records attributed to Jian Zhang.

At least 73 records · Page 4Linked to original sources

[Experience in reoperation of lumbar spinal surgery using posterior lumbar interbody fusion cage].

OBJECTIVE: To investigate the indications and surgical techniques of reoperative lumbar spinal surgery using posterior lumbar interbody fusion cage. METHODS: Seventeen cases underwent reoperative lumbar spinal surgery using posterior lumbar interbody fusion cage. The surgical methods included decompression of lumbar canal, dural and radicular conglutination release, discectomy, posterior insertion of lumbar interbody fusion cage, pedicle screw instrumentation, posterolateral lumbar fusion. Periodical follow-up was conducted for 18 months (12 - 43 months). The clinical effect was evaluated by the Macnab's criterion, and the outcome of lumbar interbody fusion was evaluated according to the Brantigan's criterion. RESULTS: Twenty-seven cages were implanted into twenty-three disc spaces (cage at L(3 - 4) in 5 cases, cage at L(4 - 5) in 8 cases, and cage at L(5)-S(1) in 4 cases). All postoperative patients ambulated after two weeks. No wound healing problems and nerve injury were found. Dural rupture occurred in 5 cases, but without occurrence of cerebrospinal fluid leakage. According to the Macnab's criterion, the preoperative lower extremity radicular symptoms and neurogenic claudication were effectively relieved in 15 cases (88.2%), and the outcomes were good or excellent in 15 cases (88.2%). According to the Brantigan's criterion no evidence of implant failure was found, and interbody fusion could be achieved about 6 months in all patients. No additional operation was needed for involved segments, and the surgical outcomes could be maintained. CONCLUSION: A good and effective method, use of posterior lumbar interbody fusion cage in reoperative lumbar spinal surgery eliminates neural compression and the discogenic pain, restore the lumbar alignment, and accomplish the internal fixation and anterior column fusion of lumbar vertebrae simultaneously.

Adult↗

Associations of apolipoprotein B with pulse pressure and glucose in Chinese families with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL), with a marked elevation of apolipoprotein B (apoB), is estimated to cause 10-20% of premature coronary artery disease. However, little data are available to demonstrate the associations of apoB with pulse pressure and glucose levels in FCHL families in China. This study was to investigate the potential influence factors for blood pressure and glucose phenotypes in FCHL families by multiple linear regression analysis. We recruited 147 FCHL relatives and 90 spouses, aged 30 to 60 years, from 42 Chinese families with FCHL. Our results showed that triglyceride and low density lipoprotein cholesterol were associated with fasting glucose levels (all P<0.05). Body mass index and glucose significantly correlated to systolic blood pressure, diastolic blood pressure, and mean arterial pressure, respectively (all P<0.05). Furthermore, apoB was significantly related to pulse pressure and glucose in FCHL families (all P<0.05). Thus, this study demonstrates that apoB is significantly associated with pulse pressure and glucose levels in FCHL families. Accordingly, our data suggest that apoB may be a candidate risk marker for pulse pressure and glucose in FCHL populations.

Adult↗

Preparation of hollow capsule-stabilized gold nanoparticles through the encapsulation of the dendrimer.

The narrow-dispersed dendrimer-encapsulated gold nanoparticles without agglomeration were prepared from the grafted-dendrimers on the surface of the silica microspheres, successively by complexation of the gold chloride anion with the nitrogen atom of the dendrimer and the reduction with sodium borohydride as reductant. The hollow capsule-stabilized gold nanoparticles were prepared through the encapsulation of dendrimer successively by LBL self-assembly process of polyelectrolytes with modified-silica as template and removal of the silica core by hydrofluoric acid. The size of gold nanoparticles was 2.3+/-0.8 nm. The catalytic activity of the capsule-stabilized gold nanoparticles was investigated in the reduction reaction of 4-nitrophenol to 4-aminophenol with sodium borohydride as reductant.

Journal Article↗

Expansion of canine bone marrow-derived endothelial progenitor cells and dynamic observation.

We cultured bone marrow-derived endothelial progenitor cells by a simple ex vivo expansion method and observed the expansion efficacy. Bone marrow mononuclear cells from five mongrel adult dogs were cultured with EGM-2MV medium in culture flasks coated with fibronectin. Morphology was observed with phase contrast microscopy, and a growth curve was constructed to evaluate the efficacy of expansion. Incorporation of Dil-ac-LDL was tested to evaluate the function. At different time points, immunocytochemical staining for flk-1, CD133, and factor VIII-related antigens was done and compared to staining of endothelial cells and mesenchymal stem cells and percentages of CD133, vascular endothelial growth factor receptor 2 (VEGFR-2), and the double-positive cells measured with flow cytometry to identify the quality and efficacy of expansion. Cluster-like attached cells grew to confluence at an average time of 10 days, and the mean number of cells harvested from 1 mL of bone marrow was (1.3 +/- 0.3) x 10(6). The cells presented a cobblestone-like appearance and took up Dil-ac-LDL. Immunocytochemistry showed that flk-1, CD133, and factor VIII-related antigens were positive. Flow cytometry showed that VEGFR-2 and CD133 double-positive cells augmented 242-fold at the tenth day. Ex vivo expansion can effectively proliferate endothelial progenitor cells from bone marrow; the expansion efficacy could meet the requirements for tissue engineering of blood vessels.

AC133 Antigen↗

On the statistical analysis of the GS-NS0 cell proteome: imputation, clustering and variability testing.

We have undertaken two-dimensional gel electrophoresis proteomic profiling on a series of cell lines with different recombinant antibody production rates. Due to the nature of gel-based experiments not all protein spots are detected across all samples in an experiment, and hence datasets are invariably incomplete. New approaches are therefore required for the analysis of such graduated datasets. We approached this problem in two ways. Firstly, we applied a missing value imputation technique to calculate missing data points. Secondly, we combined a singular value decomposition based hierarchical clustering with the expression variability test to identify protein spots whose expression correlates with increased antibody production. The results have shown that while imputation of missing data was a useful method to improve the statistical analysis of such data sets, this was of limited use in differentiating between the samples investigated, and highlighted a small number of candidate proteins for further investigation.

Algorithms↗

GAS41 interacts with transcription factor AP-2beta and stimulates AP-2beta-mediated transactivation.

Transcription factor AP-2 regulates transcription of a number of genes involving mammalian development, differentiation and carcinogenesis. Recent studies have shown that interaction partners can modulate the transcriptional activity of AP-2 over the downstream targets. In this study, we reported the identification of GAS41 as an interaction partner of AP-2beta. We documented the interaction both in vivo by co-immunoprecipitation as well as in vitro through glutathione S-transferase (GST) pull-down assays. We also showed that the two proteins are co-localized in the nuclei of mammalian cells. We further mapped the interaction domains between the two proteins to the C-termini of both AP-2beta and GAS41, respectively. Furthermore, we have identified three critical residues of GAS41 that are important for the interaction between the two proteins. In addition, by transient co-expression experiments using reporter containing three AP-2 consensus binding sites in the promoter region, we found that GAS41 stimulates the transcriptional activity of AP-2beta over the reporter. Finally, electrophoretic mobility shift assay (EMSA) suggested that GAS41 enhances the DNA-binding activity of AP-2beta. Our data provide evidence for a novel cellular function of GAS41 as a transcriptional co-activator for AP-2beta.

Binding Sites↗

Dye-labeled silver nanoshell-bright particle.

Silica beads with average diameters of 40-600 nm were prepared, and Ru(bpy)3(2+) complexes were incorporated into the beads. These beads were coated by silver layer by layer to generate porous but continuous metal nanoshells. The thicknesses of these metal shells were 5-50 nm. The emission band from the dyes in the silica cores was more narrow and the intensity was enhanced with growth of silver shell thickness due to coupling of the emission light from Ru(bpy)3(2+) in the cores with the metal plasmon from the silver shells. The enhancement of emission intensity was also dependent on the size of the silica core, showing that the enhancement efficiency decreased with an increase in the size of the silica beads. Lifetime measurements support the coupling mechanism between the dye and metal shell. This study can be used to develop novel dye-labeled metal particles with bright and narrow emission bands.

Fluorescent Dyes↗

The carboxy terminus of EmbC from Mycobacterium smegmatis mediates chain length extension of the arabinan in lipoarabinomannan.

D-Arabinofurans, attached to either a galactofuran or a lipomannan, are the primary constituents of mycobacterial cell wall, forming the unique arabinogalactan (AG) and lipoarabinomannan (LAM), respectively. Emerging data indicate that the arabinans of AG and LAM are distinguished by virtue of the additional presence of linear termini in LAM, which entails some unknown feature of the EmbC protein for proper synthesis. In common with the two paralogous EmbA and EmbB proteins functionally implicated for the arabinosylation of AG, EmbC is predicted to carry 13 transmembrane spanning helices in an integral N-terminal domain followed by a hydrophilic extracytoplasmic C-terminal domain. To delineate the function of this C-terminal domain, the embC knock-out mutant of Mycobacterium smegmatis was complemented with plasmids expressing truncated embC genes. The expression level of serially truncated EmbC protein thus induced was examined by EmbC-specific peptide antibody, and their functional implications were inferred from ensuing detailed structural analysis of the truncated LAM variants synthesized. Apart from critically showing that the smaller arabinans are mostly devoid of the linear terminal motif, beta-D-Araf(1-->2)-alpha-D-Araf(1-->5)-alpha-D-Araf(1-->5)-alpha-D-Araf, our studies clearly implicate the C-terminal domain of EmbC in the chain extension of LAM. For the first time a full range of arabinan chains as large as 18-22 Araf residues and beyond could be released intact by the use of an endogenous endo-D-arabinanase from M. smegmatis, profiled, and sequenced directly by tandem mass spectrometry. In conjunction with NMR studies, our results unequivocally show that the LAM-specific linear termini are an extension on a well defined inner branched Ara-(18-22) core. This hitherto unrecognized feature not only allows a significant revision of the structural model of LAM-arabinan since its first description a decade ago but also furnishes a probable molecular basis of selectivity in biosynthesis, as conferred by the EmbC protein.

Bacterial Proteins↗

[The clinical value of B-type natriuretic peptide in the diagnosis of left heart failure].

OBJECTIVE: To evaluate the diagnostic value of B-type natriuretic peptide (BNP) in the diagnosis of left heart failure (HF) or left ventricular systolic dysfunction. METHODS: Samples of peripheral venous blood were collected from 243 consecutive patients with left HF and 111 normal controls (control group, CG) to measured BNP level with fluorescence immunoassay method. The patients with left HF were divided into 2 groups: those with the left ventricular ejection fraction (LVEF) </= 40% (n = 111) and those with the LVEF > 40% (n = 132) according to the level of LVEF; or into 2 groups: compensated heart failure group (CHF group, at NYHA grade I - II, n = 110) and decompensated heart failure group (DHF group, at NYHA grade III - IV, n = 133) according to the New York Heart Association (NYHA) functional class. RESULTS: The plasma level of BNP of the left HF group was 292.0 ng/L, significantly higher than that of the CG (17.9 ng/L, P < 0.001). The plasma BNP of the group with the LVEF </= 40% was 471.0 ng/L, significantly than that of the group with the LVEF > 40% (138.5 ng/L, P < 0.001). The plasma BNP of the DHF group was 579.0 ng/L, significantly higher than that of the of the CHF group (84.8 ng/L, P < 0.001). The values of area under the curve (AUC) of receiver operator characteristic curve were all > 0.9 in the diagnosis of presence of HF (AUC = 0.927), HF with the LVEF </= 40% (AUC = 0.989), and DHF (AUC = 0.991), and in the differential diagnosis between CHF and DHF (AUC = 0.941). When 90.0 pg/ml was used as cutoff value to diagnose left HF, heart failure with the LVEF </= 40%, and decompensation, the positive predictive value (PPV) were 98.9%, 98.1%, and 98.5% respectively, and the negative predictive value (NPV) were 64.5%, 94.0%, and 96.5% respectively. When 50.0 pg/ml was used as the cutoff value to diagnose HF with the LVEF > 40% and compensated heart failure, the PPV were 88.0% and 84.7%, the NPV were 72.6% and 72.1% respectively. CONCLUSION: The diagnostic value of BNP is high for the diagnosis of more severely impaired LVEF and decompensated heart failure with 90.0 pg/ml as the cutoff value, and if 50.0 pg/ml is used as the cutoff value, the value is also good for the diagnosis of HF with the LVEF > 40% and compensated heart failure.

Adolescent↗

Determination of three bile acids in artificial Calculus Bovis and its medicinal preparations by micellar electrokinetic capillary electrophoresis.

A micellar electrokinetic capillary electrophoresis (MEKCE) method for the determination of cholic acid (CA), hyodeoxycholic acid (HDCA) and chenodeoxycholic acid (CDCA) in artificial Calculus Bovis and its four medicinal preparations is described. The buffer solution consisted of 40 mM disodic phosphate and 40 mM sodium dodecylsulfate (SDS) adjusted to pH 9.0. UV detection was set to 200 nm. Under optimum conditions, the analytes were baseline separated within 11min. The linear calibration range was 12.1-970 microgml(-1) for CA and 18.8-950 microgml(-1) for HDCA and CDCA, respectively. It was found that overall recoveries were within the range of 98-102%, and R.S.D.s were less than 5% for the analytes. This method, due to its convenience, high accuracy and good reproducibility can be employed in quality control of artificial Calculus Bovis and its medicinal preparations.

Animals↗

PGE2 glycerol ester, a COX-2 oxidative metabolite of 2-arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neurons.

The oxygenation of endogenous cannabinoids (eCBs) 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide by cyclooxygenase-2 (COX-2) produces novel types of prostanoids: prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs). However, the physiological function of COX-2 oxidative metabolites of eCBs is still unclear. Here we demonstrate that PGE2-G, a COX-2 oxidative metabolite of 2-AG, induced a concentration-dependent increase in the frequency ofminiature inhibitory postsynaptic currents (mIPSCs) in primary cultured hippocampal neurons, an effect opposite to that of 2-AG. This increase was not inhibited by SR141716, a CB1 receptor antagonist, but was attenuated by an IP3 or MAPK inhibitor. In addition, we also examined the effects of other prostanoids derived from COX-2 oxygenation of eCBs on mIPSCs. PGD2-G, PGF2alpha-G and PGD2-EA, but not PGE2-EA or PGF2alpha-EA, also increased the frequency of mIPSCs. The eCB-derived prostanoid-induced responses appeared to be different from those of corresponding arachidonic acid-derived prostanoids, implying that these effects are not mediated via known prostanoid receptors. We further discovered that the inhibition of COX-2 activity reduced inhibitory synaptic activity and augmented depolarization-induced suppression of inhibition (DSI), whereas the enhancement of COX-2 augmented the synaptic transmission and abolished DSI. Our results, which show that COX-2 oxidative metabolites of eCBs exert opposite effects to their parent molecules on inhibitory synaptic transmission, suggest that alterations in COX-2 activity will have significant impact on endocannabinoid signalling in hippocampal synaptic activity.

Animals↗

Nischarin as a functional imidazoline (I1) receptor.

Gene matching shows that Nischarin is a mouse homologue of human imidazoline receptor antisera-selective (IRAS) protein, a viable candidate of the imidazoline (I1) receptor. Nischarin and IRAS share the functions of enhancing cell survival, growth and migration. Bioinformatics modeling indicates that the IRAS and Nischarin may be transmembrane proteins and the convergence information raises the interesting possibility that Nischarin might serve as the I1-receptor. To test this hypothesis, we developed antibodies against the Nischarin protein, and conducted signal transduction (functional) studies with the I1-receptor agonist rilmenidine in the presence and absence of Nischarin antisense oligodeoxynucleotides (ODNs). NIH3T3 cells transfected with the Nischarin cDNA and incubated with the newly synthesized antibody expressed a 190 kD band. The antibody identified endogenous Nischarin in differentiated PC12 cells around 210 kD, which is consistent with reported findings in other cells of neuronal origin. The immunoflourescence findings showed the targeted protein to be associated with the cell membrane in PC12 cells. Nischarin ODNs abolished the expression of Nischarin in PC12 cells. Equally important, the Nischarin ODNs eliminated the production of MAPK(p42/44), a recognized signal transduction product generated by I1-receptor activation in differentiated PC12 cells. Together, the present findings suggest that Nischarin may serve as the functional I1-receptor or at least share a common signaling pathway in the differentiated PC12 cells.

Adrenergic alpha-Agonists↗

Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients.

In 10-30% of patients with classical familial adenomatous polyposis (FAP) and up to 90% of those with attenuated (<100 colorectal adenomas; AFAP) polyposis, no pathogenic germline mutation in the adenomatous polyposis coli (APC) gene can be identified (APC mutation-negative). Recently, biallelic mutations in the base excision repair gene MYH have been shown to predispose to a multiple adenoma and carcinoma phenotype. This study aimed to (i) assess the MYH mutation carrier frequency among Swiss APC mutation-negative patients and (ii) identify phenotypic differences between MYH mutation carriers and APC/MYH mutation-negative polyposis patients. Seventy-nine unrelated APC mutation-negative Swiss patients with either classical (n=18) or attenuated (n=61) polyposis were screened for germline mutations in MYH by dHPLC and direct genomic DNA sequencing. Overall, 7 (8.9%) biallelic and 9 (11.4%) monoallelic MYH germline mutation carriers were identified. Among patients with a family history compatible with autosomal recessive inheritance (n=45), 1 (10.0%) out of 10 classical polyposis and 6 (17.1%) out of 35 attenuated polyposis patients carried biallelic MYH alterations, 2 of which represent novel gene variants (p.R171Q and p.R231H). Colorectal cancer was significantly (p<0.007) more frequent in biallelic mutation carriers (71.4%) compared with that of monoallelic and MYH mutation-negative polyposis patients (0 and 13.8%, respectively). On the basis of our findings and earlier reports, MYH mutation screening should be considered if all of the following criteria are fulfilled: (i) presence of classical or attenuated polyposis coli, (ii) absence of a pathogenic APC mutation, and (iii) a family history compatible with an autosomal recessive mode of inheritance.

Adenomatous Polyposis Coli↗

Reverse of NK cytolysis resistance of type II cytokine predominant-human tumor cells.

Tumor cells suppress host immunity by secreting soluble factors, among which cytokines play important roles. Type I cytokine mRNA levels (IL-2 and IFNgamma) and type II cytokine mRNA levels (IL-4, IL-10 and IL-13) of twenty tumor cell lines and fresh tumor tissues from fifteen patients with colorectal cancer were examined by RT-PCR method. Upon analysis, tumor cells showed type II predominance and were resistant to NK cytolysis. In order to reverse the type II predominant status, type I cytokines (IL-2 or IFNgamma) and/or anti-type II cytokine antibody (IL-10 mAb) were used in an in vitro study. By this shifting treatment, type II cytokine mRNA levels of these tumor cells were decreased, moreover, the sensitivity to natural cytolysis of these cells was then significantly increased. Thus, tumor-induced type II cytokine dominance is possibly to be shifted into type I status, which benefits the anti-tumor natural immunity.

Adenocarcinoma↗

SPAN-Xb expression in myeloma cells is dependent on promoter hypomethylation and can be upregulated pharmacologically.

SPAN-Xb is a novel cancer-testis antigen in multiple myeloma (MM). In this study, we determined the mechanisms regulating SPAN-Xb expression in MM. SPAN-Xb promoter sequence was first cloned into the CAT-reporter vector to determine the role of promoter methylation in the regulation of gene expression. Tumor cells were treated with 5-azacytidine and a panel of cytokines were used to determine their ability to induce SPAN-Xb expression. Bisulfite conversion with sequence analysis was applied to a panel of tumor cells and normal tissues to correlate the CpG dinucleotide hypomethylation and SPAN-Xb expression. We found that SPAN-Xb promoter function could be silenced by methylation. 5-Azacytidine induced promoter hypomethylation and resulted in SPAN-Xb expression, at both the transcript and protein levels. Hypomethylation of the CpG dinucleotides at positions -310, -307, -299 and -221 within the SPAN-Xb promoter strongly predict for SPAN-Xb expression. Both IL-7 and GM-CSF were also able to upregulate the expression of SPAN-Xb in myeloma cells, but only after the promoter sequence has been hypomethylated. Our results provide the first evidence showing the role of promoter methylation in the primary regulation of SPAN-Xb and the ability of IL-7 and GM-CSF to further enhance SPAN-Xb gene and protein expression in myeloma cells.

Azacitidine↗

Folding mechanism of beta-hairpins studied by replica exchange molecular simulations.

The folding process of trpzip2 beta-hairpin is studied by the replica exchange molecular dynamics (REMD) and normal MD simulations, aiming to understand the folding mechanism of this unique small, stable, and fast folder, as well as to reveal the general principles in the folding of beta-hairpins. According to our simulations, the TS ensemble is mainly characterized by a largely formed turn and the interaction between the inner pair of hydrophobic core residues. The folding is a zipping up of hydrogen bonds. However, the nascent turn has to be stabilized by the partially formed hydrophobic core to cross the TS. Thus our folding picture is in essence a blend of hydrogen bond-centric and hydrophobic core-centric mechanism. Our simulations provide a direct evidence for a very recent experiment (Du et al., Proc Natl Acad Sci USA 2004;101:15915-15920), which suggests that the turn formation is the rate-limiting step for beta-hairpin folding and the unfolding is mainly determined by the hydrophobic interactions. Besides, the relationship between hydrogen bond stabilities and their relative importance in folding are investigated. It is found that the hydrogen bonds with higher stabilities need not play more important roles in the folding process, and vice versa.

Computer Simulation↗