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Shu Zhang

Publications and source records attributed to Shu Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes.

BACKGROUND: The gene encoding acyloxyacyl hydroxylase (AOAH), an enzyme that hydrolyzes secondary fatty acyl chains of LPS, is localized on chromosome 7p14-p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has been previously reported. OBJECTIVE: We hypothesized that variants in AOAH are associated with asthma and related phenotypes. Because both AOAH and soluble CD14 respond to LPS, we tested for gene-gene interaction. METHODS: We investigated the association between 28 single nucleotide polymorphisms throughout the AOAH gene and asthma, concentrations of tIgE, the ratio of IL-13/IFN-gamma, and soluble CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n = 834). Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH genotype. RESULTS: Significant effects were observed for all 4 phenotypes and AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon 13 boundary/intron 13 region) by means of single-marker and haplotype analyses, with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and log[tIgE] (P = .006). There was no difference in AOAH expression levels by AOAH genotype for any of the markers. Comparing genotypic distributions at both the AOAH marker rs2727831 and CD14(-260)C >T raises the possibility of gene-gene interaction (P = .006-.036). CONCLUSION: Our results indicate that polymorphisms in markers within the AOAH gene are associated with risk of asthma and associated quantitative traits (IgE and cytokine levels) among asthmatic subjects and their families in Barbados, and there is an interactive effect on tIgE and asthma concentrations between an AOAH marker and the functional CD14(-260)C >T polymorphism. CLINICAL IMPLICATIONS: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.

Asthma↗
PubMed2006

Assessment of cardiac function and synchronicity in subjects with isolated bundle branch block using Doppler imaging.

BACKGROUND: Using tissue Doppler imaging and conventional echocardiographic technique, we examined the cardiac function and synchronicity in individuals with isolated right bundle branch block (RBBB) or left bundle branch block (LBBB) and assessed the relationship between QRS duration and synchronicity. METHODS: Subjects with isolated RBBB (n = 20), LBBB (n = 10) and normal controls (n = 20) were studied with conventional echocardiography and tissue Doppler imaging. The difference between aortic and pulmonary preejection intervals was defined as interventricular delay. Parameters in septum and lateral wall were measured using tissue Doppler imaging, including peak sustained systolic velocity (S(M)), peak early (E(M)) and late (A(M)) diastolic velocities as well as time to peak velocities (T(S), T(E) and T(A)). RESULTS: Subjects with LBBB had lower S(M) and longer T(S) than did the RBBB and control groups (P < 0.05, P < 0.001 respectively). A significant difference was observed in E(M), being the lowest in the LBBB and the highest in the control group (P < 0.05). Moreover, T(E) was longer in the LBBB group compared with the other two groups (P < 0.001). Both A(M) and T(A) were similar among three groups (P > 0.05). In the bundle branch block groups, one ventricle lagged about 40 ms behind the other. A significant correlation was found between interventricular delay and QRS duration (r = 0.713, P < 0.001). CONCLUSIONS: Cardiac ventricles were not well synchronized with one ventricle lagging about 40 ms behind the other in subjects with LBBB or RBBB, even though only LBBB group showed barely perceptible, impaired cardiac function. In addition, QRS duration and cardiac asynchronicity were positively correlated.

Adult↗
PubMed2006

Incidence and causes of inappropriate detection and therapy by implantable defibrillators of cardioversion in patients with ventricular tachyarrhythmia.

BACKGROUND: Implantable cardioverter defibrillator (ICD) is the only effective therapy in patients with life threatening ventricular arrhythmias. Inappropriate detection and therapy by ICDs are the most common causes of side effects that affect the quality of life in ICD recipients. This study evaluated the incidence and causes of inappropriate detection and therapy by ICDs in patients in our hospital. METHODS: From January 2000 to December 2005, fifty patients who received ICD implantation for ventricular arrhythmias for prevention of sudden cardiac death were evaluated in this study. Each ICD was programmed using clinical arrhythmic and cardiac data of the patient before discharge. Patients were followed up by standard schedule after implantation and all data retrieved from each device were collected and saved for further analysis. RESULTS: No arrhythmic event was detected in 12/50 (24%) patients during the period of follow-up. Among the remaining patients, 11 (22%) experienced inappropriate detections and therapies during follow-up in this study. ICD detected 383 ventricular tachyarrhythmia (VT) and 108 ventricular fibrillation (VF) episodes and delivered 678 therapies. In VT group, ICD delivered 413 antitachycardiac pacings (ATPs) and 118 shocks, among which 78 ATPs and 9 shocks were initiated by 55/383 (14.3%) inappropriate detections. In VF group ICD delivered 147 shocks, among which 56 shocks were initiated by 28/108 (26.9%) inappropriate detections. Overall, more than 50% of these episodes were caused by atrial fibrillation (AF) with rapid ventricular response, followed by electromagnetic or myopotential interference. In addition, most inappropriate therapies occurred within one year after ICD implantation. CONCLUSIONS: About one fifth of patients experienced ICD inappropriate detection and therapy after implantation. The main cause was AF with rapid ventricular response, followed by electromagnetic or myopotential interference.

Adult↗
PubMed2006

Complications of cardiac resynchronization therapy in patients with congestive heart failure.

BACKGROUND: Previous clinical studies have suggested that patients with congestive heart failure and intraventricular conduction delay could benefit from cardiac resynchronization therapy (CRT). Implantation of left ventricular lead is a complex procedure with some potential for complications. This study was conducted to analyse the complications of CRT in patients with congestive heart failure. METHODS: Totally 117 patients, 86 males and 31 females, mean age of 53 years, with congestive heart failure and intraventricular conduction delay were enrolled in this study. Venography was performed on all patients. Different types of coronary sinus leads were used to pace the left ventricle. RESULTS: Left ventricular lead was attempted to implant through coronary sinus for all the 117 patients and was successfully implanted in 111 patients. The success rate was 94.9%. Main complications rate was 6.8%, including coronary sinus dissection in 4 patients, phrenic nerve stimulation required lead repositioning in 2 patients and lead dislodgement in 2 patients. CONCLUSIONS: It is feasible and safe to pace left ventricle through coronary sinus. However, there are some procedural complications.

Angioplasty, Balloon, Coronary↗
PubMed2006

Left posterior fascicular block: a new endpoint of ablation for verapamil-sensitive idiopathic ventricular tachycardia.

BACKGROUND: Verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) with right bundle branch block configuration and left-axis deviation is known to be due to re-entry mechanism but the exact nature of reentrant circuit in ILVT is not fully elucidated. Radiofrequency (RF) ablation was applied during ventricular tachycardia (VT) and termination of the VT or abolishing the inducibility of the tachycardia was used as an endpoint for successful RF. In this study, the left posterior fascicular block in surface electrocardiogram (ECG) was used as a new endpoint of ablation to cure ILVT. METHODS: Electrophysiological studies and radiofrequency ablation were performed in 39 consecutive patients [30 men, 9 women; age ranging from 10 to 64 years, mean (29 +/- 16) years] with verapamil-sensitive ILVT and structurally normal hearts. VT could be terminated by the intravenous administration of verapamil in all patients. The target site was the midseptum of LV where the earliest Purkinje potentials were recorded during VT. RF current was applied to the target site with or without late diastolic potential (LDP) during sinus rhythm in 37 patients and during VT in 2 patients to meet the ablation endpoint: the left posterior fascicular block in the surface ECG. RESULTS: Thirty-seven patients with ILVT had been treated by RF ablation during sinus rhythm and two had been treated during VT. All of them met the endpoint of the left posterior fascicular block. Thirty-eight cases were symptom-free without medications during the follow-up period (range from 3 to 95 months, median 17 months). One patient developed a clinical recurrence and the left posterior fascicular block in surface ECG disappeared. The patient received another treatment. The endpoint was met and the procedure was successful. CONCLUSIONS: The left posterior fascicular block in surface ECG used as an endpoint of RF ablation to treat ILVT is effective. It is important especially in those patients whose VT can not be induced or the inducible condition is unstable. The effective endpoint implied that the left posterior fascicle might be a critical part of the re-entrant circuit.

Adolescent↗
PubMed2006

Comparison of percutaneous transluminal septal myocardial ablation versus septal myectomy for the treatment of patients with hypertrophic obstructive cardiomyopathy--a meta analysis.

BACKGROUND: The effects of percutaneous transluminal septal myocardial ablation (PTSMA) with septal myectomy in patients with hypertrophic obstructive cardiomyopathy (HOCM) are not thoroughly compared. METHODS: Three articles comparing the effects of PTSMA and septal myectomy treatment for HOCM were identified from a search in Pubmed, and a meta analysis was conducted. RESULTS: 177 patients (86 underwent PTSMA and 91 underwent septal myectomy) were included. Interventricular septum thickness was decreased from 22.1 to 15.1 mm (p<0.05) in PTSMA group and from 22.0 to 13.9 mm (p<0.05) in septal myectomy group; left ventricular end-diastolic dimension was increased from 41.8 to 45.2 mm (p<0.05) in PTSMA group and from 41.8 to 43.9 mm (p<0.05) in septal myectomy group; NYHA class was improved from 3.17 to 1.47 (p<0.05) in PTSMA group and from 2.97 to 1.36 (p<0.05) in septal myectomy group; there were no differences in the two groups. However, left ventricular outflow tract gradient was decreased from 76.0 to 15.7 mm Hg (p<0.05) in PTSMA group and from 74.7 to 9.4 mm Hg (p<0.05) in septal myectomy group and the effect of septal myectomy was better than PTSMA (p<0.05). CONCLUSIONS: The effects of septal myectomy treatment for HOCM are better with regard to relief of LVOT gradient, and lower risk of pacemaker requirement, compared to PTSMA. Large randomized clinical trials further comparing the two treatments are suggested.

Adult↗
PubMed2006

Activation of kinase pathways in MCF-7 cells by 17beta-estradiol and structurally diverse estrogenic compounds.

17beta-Estradiol (E2) activates non-genomic pathways in MCF-7 cells, and this study investigates the effects of structurally-diverse estrogenic compounds on activation of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI3-K), protein kinase C (PKC), PKA, and calcium calmodulin-dependent kinase IV (CaMKIV). Activation of kinases was determined by specific substrate phosphorylation and transactivation assays that were diagnostic for individual kinases. The compounds investigated in this study include E2, diethylstilbestrol (DES), the phytoestrogen resveratrol, and the following synthetic xenoestrogens, bisphenol-A (BPA), nonylphenol, octylphenol, endosulfan, kepone, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), and 2',3',4',5'-tetrachloro-4-biphenylol (HO-PCB-Cl(4)). With the exception of resveratrol, all the compounds activated PI3-K and MAPK. Activation of PKC by the xenoestrogens was structure-dependent since resveratrol, kepone and HO-PCB-Cl(4) were inactive and only minimal activation of PKA was observed. CaMKIV was activated only by E2 and DES, and HO-PCB-Cl(4) was a potent inhibitor of CaMKIV-dependent activity. These results demonstrate that activation of estrogen receptor-alpha-mediated non-genomic pathways by estrogenic compounds in MCF-7 cells is structure-dependent and can result in activation or inhibition of kinase activities.

Benzhydryl Compounds↗
PubMed2006

Positive pressure ventilation treatment reduces plasma levels of amino terminal-pro brain natriuretic peptide in congestive heart failure patients with sleep apnea.

BACKGROUND: The purpose of the present study was to assess the short-term effects of positive pressure ventilation (PPV) on plasma amino terminal-pro brain natriuretic peptide (NT-proBNP) levels in patients with congestive heart failure (CHF) and sleep apnea (SA). METHODS AND RESULTS: Polysomnography was performed in 105 CHF patients. Twenty-six patients with CHF and SA were randomly assigned to a control group or a PPV group. Patients in the higher New York Heart Association classes had higher plasma levels of NT-proBNP. The plasma NT-proBNP concentration in the PPV group decreased. CONCLUSION: Plasma NT-proBNP levels reflect the severity of CHF, and PPV can decrease plasma NT-proBNP levels in patients with CHF and SA.

Adult↗
PubMed2006

[Construction and identification of HBD-2 transgenic mice].

Human beta defensin 2 (HBD-2) may play an important role in human defense against infection. Its antimicrobial capacity has been fully documented in in vitro study. In order to evaluae its in vivo effects, we developed an HBD-2 transgenic mouse model. The HBD-2 minigene containing CMV promoter, full length of HBD-2 cDNA and BGH polyA tail was generated by PCR amplification and introduced into the fertilized oocytes of C57 X ICR hybridized mouse by microinjection, and offspring were produced. DNA was isolated from the tails of the mouse pups, and the HBD-2 minigene incorporation was analyzed by PCR using HBD-2 specific primers. The HBD-2 gene expression in the multi-tissues of transgenic mice was determined at mRNA level by RT-PCR and at peptide level by immunohistological staining with the use of HBD-2 monoclonal antibody. The results showed that among 17 F0 transgenic mice, HBD-2 positive signal was determined by PCR in 4 mice, suggesting that HBD-2 minigene has been incorporated into the offspring mice. Meanwhile, a widespread expression of HBD-2 mRNA and peptide was detected in the F1 transgenic mice's multi-tissues such as trachea, lung, intestine, esophagus, testis, spleen, skin, endothelium and brain.

Animals↗
PubMed2006

[The effects of noninvasive positive pressure ventilation treatment on plasma concentration of amino terminal-pro brain natriuretic peptide in congestive heart failure in patients with sleep apnea].

OBJECTIVE: Sleep apnea (SA) exerts adverse effects in patients with congestive heart failure (CHF). Amino terminal-pro brain natriuretic peptide (NT-proBNP) is a useful target of CHF treatment. The purpose of this study was to assess the short-term effect of positive pressure ventilation (PPV) on the plasma concentration of NT-proBNP in patients with both CHF and SA. METHODS: One hundred and five patients diagnosed with CHF participated in the study. Medical history was recorded, and Doppler echocardiography and overnight polysomnography were performed. Seventy-seven patients were diagnosed as having SA. Patients with CHF and SA were randomly assigned to receive medical therapy alone (12 patients) or with the addition of PPV (14 patients) for 2 - 5 days. RESULTS: Plasma NT-proBNP concentration was measured in 77 patients with CHF and SA. The plasma level of NT-proBNP was associated with the severity of CHF. Subjects with higher degree of NYHA class showed higher a level of NT-proBNP. After PPV treatment, the apnea-hypopnea index decreased (P < 0.001), the lowest SaO2 increased (P < 0.001), and the plasma concentration of NT-proBNP decreased as compared to the baseline levels (P < 0.05). CONCLUSION: The plasma levels of NT-proBNP could reflect the severity of CHF, and PPV treatment could decrease the plasma NT-proBNP level in patients with CHF and SA.

Adult↗
PubMed2006

[Effects of absorption enhancers on intestinal absorption of lumbrokinase].

AIM: To explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption. METHODS: The absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo. RESULTS: YJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD. CONCLUSION: The results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.

Administration, Oral↗
PubMed2005

16S rRNA gene probe quantitates residual host cell DNA in pharmaceutical-grade plasmid DNA.

The development and widespread use of DNA-based vaccination against infectious pathogens have been a great triumph of medical science. Quality control of DNA vaccines as biopharmaceutical productions is a problem to solve. Residual genomic DNA of engineering bacteria has been identified as a potential risk factor, so whose level must be controlled under the regulatory standards. We report a dot-blot hybridization method to detect residual host cell DNA in purified DNA vaccines. The assay utilizes PCR amplified and digoxigenin-labeled Escherichia coli 16S rRNA gene as probe. The sensitivity of the dot-blot hybridization assay with E. coli 16S rRNA gene probe was evaluated in comparison with single copy UidR gene probe. The optimized dot-blot hybridization assay had both low background and a suitable sensitivity, detecting 10 pg of residual E. coli DNA. The method is suitable in the routine use of measuring the levels of residual E. coli DNA in the pharmaceutical-grade DNA vaccine.

DNA↗
PubMed2005

Influence of leukotriene pathway polymorphisms on response to montelukast in asthma.

RATIONALE: Interpatient variability in montelukast response may be related to variation in leukotriene pathway candidate genes. OBJECTIVE: To determine associations between polymorphisms in leukotriene pathway candidate genes with outcomes in patients with asthma receiving montelukast for 6 mo who participated in a clinical trial. METHODS: Polymorphisms were typed using Sequenom matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass array spectrometry and published methods; haplotypes were imputed using single nucleotide polymorphism-expectation maximization (SNP-EM). Analysis of variance and logistic regression models were used to test for changes in outcomes by genotype. In addition, chi(2) and likelihood ratio tests were used to test for differences between groups. Case-control comparisons were analyzed using the SNP-EM Omnibus likelihood ratio test. MEASUREMENTS: Outcomes were asthma exacerbation rate and changes in FEV(1) compared with baseline. RESULTS: DNA was collected from 252 participants: 69% were white, 26% were African American. Twenty-eight SNPs in the ALOX5, LTA4H, LTC4S, MRP1, and cysLT1R genes, and an ALOX5 repeat polymorphism were successfully typed. There were racial disparities in allele frequencies in 17 SNPs and in the repeat polymorphism. Association analyses were performed in 61 whites. Associations were found between genotypes of SNPs in the ALOX5 (rs2115819) and MRP1 (rs119774) genes and changes in FEV(1) (p < 0.05), and between two SNPs in LTC4S (rs730012) and in LTA4H (rs2660845) genes for exacerbation rates. Mutant ALOX5 repeat polymorphism was associated with decreased exacerbation rates. There was strong linkage disequilibrium between ALOX5 SNPs. Associations between ALOX5 haplotypes and risk of exacerbations were found. CONCLUSIONS: Genetic variation in leukotriene pathway candidate genes contributes to variability in montelukast response.

Acetates↗
PubMed2005

The C-terminal region of S100A4 is important for its metastasis-inducing properties.

The EF-hand protein, S100A4, binds calcium ions and interacts specifically in vitro with protein targets. Elevated levels of S100A4 have been shown to produce a metastatic phenotype in independent models of breast cancer. The presence of S100A4 in the carcinoma cells of patients with different carcinomas is associated with reduced patient survival. In order to identify the region of the S100A4 molecule that is responsible for its metastasis-inducing properties, specific mutant S100A4 genes and proteins have been produced which contain targeted mutations to the two calcium-binding sites and a deletion of the last 15 amino-acid residues of the protein. The ability of the mutant proteins to bind to a potential specific target in vitro, nonmuscle myosin heavy chain, is correlated with their ability to cause motile, invasive and metastatic phenotypes. Mutation of the C-EF hand of S100A4 virtually abolished calcium binding, and motility/invasion in vitro, abolished interaction with a molecular target, and reduced metastasis induction by 2.5-3-fold. However, deletion of the last 15 amino acids of S100A4 reduced motility/invasion, target binding and metastasis-induction to similar extents as the C-EF-hand mutant, but reduced calcium binding by only 26%. The results suggest that the ability to interact with protein target(s) is important in S100A4-induced metastasis.

Animals↗
PubMed2005

Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype.

AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901) and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism, and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells. METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay. RESULTS: Telomerase activity was detected in well, moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively). Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 mumol/L, and was entirely inhibited at 10 mumol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901 gastric cancer cell lines (the inhibition ratio was 40.89% and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0.05). Apoptosis of SGC-7901 and MKN-45 cells was detected not only by morphology and TUNEL assay but also by flow cytometry. The apoptotic rate reached 33.56% for SGC-7901 cells and 44.75% for MKN-45 cells. CONCLUSION: The viability and proliferation of gastric cancer cells can be inhibited by antisense telomerase oligomers. The growth inhibition of gastric cancer cells is correlated with concentration, time and sequence specialty of antisense oligomers. The inhibition mechanism of antisense human telomerase oligomers depends not only on the sequence specialty but also on the biological characteristics of gastric cancer cell lines.

Apoptosis↗
PubMed2005

Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes.

Increased levels of the homodimeric calcium-binding protein, S100A4, have been shown to cause a metastatic phenotype in at least three independent model systems of breast cancer and its presence in carcinoma cells has been shown to be associated with a reduction in the survival of patients suffering from a range of different cancers. S100A4 has been shown to interact in vitro with another member of the S100 family of proteins, S100A1. The purpose of the present study was to find out whether S100A1 could affect S100A4 function. Fluorescence resonance energy transfer was used to show the interaction of S100A4 and S100A1 in living cells and the binding affinities between S100A4 and S100A1 were determined using a biosensor. S100A1 reduced the S100A4 inhibition of nonmuscle myosin A self-association and phosphorylation in vitro. S100A1 reduced S100A4 induced motility and growth in soft agar and metastasis in vivo. The results show for the first time that interactions between different S100 proteins can affect cancer-related activity, and that the presence of S100A1 protein in carcinoma cells might modulate the effect of S100A4 on their metastatic abilities.

Animals↗