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Biomedical subjects

Qing Zhang

Publications and source records attributed to Qing Zhang.

At least 109 records · Page 6Linked to original sources

Independent and incremental prognostic value of early mitral annulus velocity in patients with impaired left ventricular systolic function.

OBJECTIVES: This study sought to investigate the incremental prognostic value of non-invasive measures of early myocardial relaxation and left ventricular diastolic pressure (LVDP) in patients with impaired left ventricular (LV) systolic function. BACKGROUND: The early diastolic mitral annulus velocity (Em) reflects myocardial relaxation, and the combined ratio of the early transmitral flow velocity (E) to Em (E/Em) >15 correlates well with elevated mean LVDP. It is unknown if these new indexes will predict poorer survival in patients with LV systolic dysfunction. METHODS: Echocardiograms were prospectively obtained in 182 patients with impaired LV systolic function, defined as an LV ejection fraction <0.50. The end point was cardiac mortality. The majority of this patient sample (80%) has been reported on in a previous publication. RESULTS: After a median 48 months' follow-up, Em emerged as an independent predictor of survival (hazard ratio 0.61, 95% confidence interval 0.45 to 0.82). An Em <3 cm/s was associated with a significantly excess mortality (log-rank statistic 9.36, p = 0.002), and this measurement added incremental prognostic value to standard indexes of systolic or diastolic function, including a deceleration time <140 ms and an E/Em >15 (p = 0.038). CONCLUSIONS: Early diastolic mitral annulus velocity is a powerful predictor of cardiac mortality in patients with LV systolic impairment; Em <3 cm/s emerged as the best prognosticator in long-term follow-up, incremental to other clinical or echocardiographic variables, including the ratio E/Em.

Aged↗

Assessment of the effect of cardiac resynchronization therapy on intraventricular mechanical synchronicity by regional volumetric changes.

A new echocardiographic technology, the timing of regional volumetric changes by 3-dimensional echocardiography, was applied to assess intraventricular mechanical synchronicity in 13 patients who had received cardiac resynchronization therapy (CRT). When biventricular pacing was withheld, left ventricular (LV) asynchrony occurred as reflected by these echocardiographic parameters, whereas LV volume increased and the ejection fraction decreased. Further studies are needed to explore whether this novel method can be used to select suitable candidates for CRT and to predict a favorable response.

Cardiac Pacing, Artificial↗

The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema.

The Protein Data Bank (PDB) is the central worldwide repository for three-dimensional (3D) structure data of biological macromolecules. The Research Collaboratory for Structural Bioinformatics (RCSB) has completely redesigned its resource for the distribution and query of 3D structure data. The re-engineered site is currently in public beta test at http://pdbbeta.rcsb.org. The new site expands the functionality of the existing site by providing structure data in greater detail and uniformity, improved query and enhanced analysis tools. A new key feature is the integration and searchability of data from over 20 other sources covering genomic, proteomic and disease relationships. The current capabilities of the re-engineered site, which will become the RCSB production site at http://www.pdb.org in late 2005, are described.

Databases, Protein↗

Genome-wide expression profiling and identification of gene activities during early flower development in Arabidopsis.

We have used oligonucleotide microarrays to detect Arabidopsis gene expression during early flower development. Among the 22,746 genes represented on the Affymetrix ATH1 chip, approximately 14,660 (approximately 64.5%) genes were expressed with signal intensity at or more than 50 in each of the six organs/structures examined, including young inflorescences (floral stages 1-9), stage-12 floral buds, developing siliques, leaves, stems, and roots. 17,583 genes were expressed with an intensity at or above 50 in at least one tissue, including 12,245 genes that were expressed in all the six tissues. Comparison of genes expressed between young inflorescence or stage-12 floral buds with other tissues suggests that relatively large numbers of genes are expressed at similar levels in tissues that are related morphologically and/or developmentally, as supported by a cluster analysis with data from two other studies. Further analysis of the genes preferentially expressed in floral tissues has uncovered new genes potentially involved in Arabidopsis flower development. One hundred and four genes were determined to be preferentially expressed in young inflorescences, including 22 genes encoding putative transcription factors. We also identified 105 genes that were preferentially expressed in three reproductive structures (the young inflorescences, stage-12 floral buds and developing siliques), when compared with the vegetative tissues. RT-PCR results of selected genes are consistent with the results from these microarrays and suggest that the relative signal intensities detected with the Affymetrix microarray are reliable estimates of gene expression.

Analysis of Variance↗

Improvement of serum NT-ProBNP predicts improvement in cardiac function and favorable prognosis after cardiac resynchronization therapy for heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) is now an established therapy for patients with advanced heart failure with electromechanical delay, although nonresponders have been observed. Because natriuretic peptides are relevant markers to reflect the severity of heart failure and filling pressure of cardiac chambers, it may be helpful to assess the efficacy of CRT. METHODS AND RESULTS: Forty-two patients with heart failure with QRS of >120 msec were recruited; their serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at baseline and at 1 and 3 months after CRT. There was a reduction in NT-proBNP level 1 month after CRT (2655 +/- 2242 pg/mL vs 2149 +/- 2033 pg/mL; P = .03), which was further reduced at 3 months (1473 +/- 1786 pg/mL; P < .001 vs baseline). The reduction of NT-proBNP correlated with the change of left ventricular (LV) end-systolic volume (r = 0.53; P = .001) or LV ejection fraction ( r = -0.49; P = .002) and with improvement in exercise capacity after CRT for 3 months (r = 0.50; P = .002). The patients were classified by the degree of reduction in NT-proBNP as group 1 (reduction of > or =50% vs baseline; n = 19) and group 2 (reduction of <50% vs baseline; n = 23). The degree of LV reverse remodeling (-31.8 +/- 24.7 mL vs -12.6 +/- 19.2 mL; P = .007) and gain in LV ejection fraction (+12.5% +/- 8.8% vs +4.6% +/- 5.8%; P = .002) were significantly better in group 1 than group 2. Both the all-cause mortality rate (Log-rank chi 2 = 4.01; P = .04) and the composite end-point of mortality rate or hospitalization rate for cardiovascular causes (Log-rank chi 2 = 4.31; P = .02) were significantly lower in group 1 than in group 2. CONCLUSION: Serial monitoring of NT-proBNP may be helpful to predict a favorable outcome after CRT. Those who had a reduction of NT-proBNP level of >/=50% were more likely to exhibit a favorable response.

Aged↗

A practical approach to the degradation of polychlorinated biphenyls in transformer oil.

A practical and efficient disposal method for hydrodechlorination of polychlorinated biphenyls (PCBs) in transformer oil is reported. Transformer oil containing PCBs was treated by nanometric sodium hydride (nano-NaH) and transition metal catalysts. High destruction and removal efficiency (89.8%) can be attained by nano-NaH alone under mild conditions. The process exhibits apparent characteristics of a first order reaction. The reductive ability of nano-NaH was enhanced by the addition of transition metal catalysts. In the presence of TiCl4, 99.9% PCBs was hydrodechlorinated. The complex reducing reagents, Ni(OAc)2+i-PrONa, show extra hydrodechlorinating activity for di-chlorinated biphenyls.

Catalysis↗

Prediction of octanol--air partition coefficients of semivolatile organic compounds based on molecular connectivity index.

A new method has been developed to describe the quantitative relationship between the octanol-air partition coefficients and molecular connectivity indexes of semivolatile organic compounds such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated naphthalenes (PCNs), polycyclic aromatic hydrocarbons (PAHs), chlorobenzenes (CBs), polybrominated diphenyl ethers (PBDEs). The stepwise multiple linear regression was used to derive six equations with correlation coefficients greater than 0.99 except for PBDEs' (0.96). The largest relative error is 4.6%, and the standard deviation is less than 1.83 log units. Compared with the data obtained from the relevant experiments, the results of prediction are very accurate.

Air↗

Distribution patterns of PCDD/Fs in chlorinated chemicals.

The purpose of this research was to determine polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in five chlorinated chemicals (phthalocyanine copper, phthalocyanine green, chloranil-1 and 2, and triclosan), and to compare their 2,3,7,8-tetrachlordibenzo-IpI-dioxin equivalents (TEQ). The distribution patterns of total PCDD/Fs and 2,3,7,8-substituted PCDD/Fs were elucidated in detail. The TEQ values of toxic PCDD/Fs in all chemicals were in the range of 5.03-1379.55 ng I-TEQ/kg. The contribution of OCDD and OCDF in phthalocyanine green was 75% of the total TEQ. For chloranils, the maximum contribution of toxic PCDD/Fs was from 2,3,7,8-substituted HxCDF and 2,3,7,8-substituted HpCDF. The TEQ of HxCDF and HpCDF in chloranil-1 was 90% and in chloranil-2 was 71%. And the toxic contribution increased with the degree of chlorination for PCDFs.

Anti-Infective Agents, Local↗

Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCP-mediated proteolytic processing.

Hedgehog (Hh) proteins govern animal development by regulating the Gli/Ci family of transcription factors. In Drosophila, Hh signaling blocks proteolytic processing of full-length Ci to generate a truncated repressor form. Ci processing requires sequential phosphorylation by PKA, GSK3, and a casein kinase I (CKI) family member(s). Here we show that Double-time (DBT)/CKIepsilon and CKIalpha act in conjunction to promote Ci processing. CKI phosphorylates Ci at three clusters of serine residues primed by PKA and GSK3 phosphorylation. CKI phosphorylation of Ci confers binding to the F-box protein Slimb/beta-TRCP, the substrate recognition component of the SCF(Slimb/beta-TRCP) ubiquitin ligase required for Ci processing. CKI phosphorylation sites act cooperatively to promote Ci processing in vivo. Substitution of Ci phosphorylation clusters with a canonical Slimb/beta-TRCP recognition motif in beta-catenin renders Slimb/beta-TRCP binding and Ci processing independent of CKI. We propose that phosphorylation of Ci by CKI creates multiple Slimb/beta-TRCP binding sites that act cooperatively to recruit SCF(Slimb/beta-TRCP).

Amino Acid Sequence↗

Four-day Bravo pH capsule monitoring with and without proton pump inhibitor therapy.

BACKGROUND & AIMS: Ambulatory pH testing often is used to guide the management of reflux symptoms that do not respond to proton pump inhibitor (PPI) therapy and to evaluate the contribution of acid reflux to atypical symptoms. Controversy exists as to whether such clinical studies are performed optimally off or on PPI therapy. The aim of the present study was to determine the feasibility of 4-day pH recordings using a pH system that would encompass time periods both before and during PPI therapy. METHODS: Eighteen patients underwent 4-day ambulatory pH testing using 2 separate receivers calibrated to a single Bravo pH capsule. Rabeprazole was administered on days 2-4 of the study (20 mg orally twice a day). RESULTS: Indications for pH testing were refractory heartburn, chest pain, or chronic cough. pH recordings showed that 9 patients (53%) had esophageal acid exposure values that exceeded 4% on day 1 and 7 patients (41%) had values that exceeded 5.3%. Patients showed significant and progressive reductions in acid exposure on days 2-4 of the recording period. Of the 7 patients with quantitatively abnormal levels of acid exposure on day 1, 86% had normalization by day 3. CONCLUSIONS: Prolonged, esophageal pH recordings using the Bravo pH system are feasible and allow for combined testing both off and on a therapeutic trial of PPI. Such studies may allow for the acquisition of complementary information in a single test that may be useful in the management of patients with suspected gastroesophageal reflux disease symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Antinociceptive property of tegaserod in a rat model of chronic visceral hypersensitivity.

OBJECTIVE: To establish a model of chronic visceral hypersensitivity in rats and to investigate the effect of tegaserod, a partial 5-hydroxytryptamine-4 receptor agonist, on visceral hypersensitivity. METHODS: Neonate Sprague-Dawley rats at 8-21 days after birth underwent colorectal distension once daily. Adult rats aged 8-10 postnatal weeks underwent colorectal distension and the abdominal withdrawal reflex (AWR) during the distension was determined. The AWR score was recorded before and after intraperitoneal administration of either tegaserod (treatment group: 0.3 mg/kg) or vehicle (control group). RESULTS: Changes in the AWR score were dependent on the pressure intensity of the colorectal distension (P < 0.01). At pressures of 40, 60 and 80 mmHg, the AWR scores in the model rats with visceral hypersensitivity were significantly higher than those recorded in the control group (1.95 +/- 0.16 vs 1.35 +/- 0.15, 2.82 +/- 0.12 vs 2.17 +/- 0.13, 3.20 +/- 0.14 vs 2.59 +/- 0.14, P < 0.01). Compared with the controls, tegaserod significantly decreased the AWR scores at the distension pressures of 40, 60 and 80 mmHg (1.95 +/- 0.50 vs 1.32 +/- 0.55, 3.05 +/- 0.48 vs 2.32 +/- 0.54, 3.25 +/- 0.63 vs 2.77 +/- 0.51, P < 0.05). CONCLUSIONS: Adult rats can develop chronic visceral hypersensitivity after transient colorectal mechanical irritation during their postnatal period. Tegaserod increases the pain threshold to noxious stimuli, suggesting an antinociceptive property in its effect on visceral hypersensitivity.

Animals↗

Understanding nonresponders of cardiac resynchronization therapy--current and future perspectives.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is now an established nonpharmacologic therapy for advanced heart failure with electromechanical delay. Despite compelling evidence of the benefits of CRT, one troubling issue is the lack of a favorable response in about one-third of patients. METHODS AND RESULTS: Currently, there is no unifying definition of responders, and published data were based on acute hemodynamic changes, chronic left ventricular reverse remodeling, as well as the intermediate or long-term clinical response. The lack of improvement with CRT can be due to many factors including the placement of the left ventricular pacing lead in an inappropriate location, the absence of electrical conduction delay or mechanical dyssynchrony despite wide QRS complexes, and possibly failure to optimize the CRT settings after device implantation. In acute hemodynamic studies, placing the left ventricular leads at the free wall region has been suggested to generate the best pulse pressure and positive dp/dt. The degree of mechanical dyssynchrony has recently been assessed noninvasively in CRT patients by echocardiography and in particular by tissue Doppler imaging. These studies suggested that responders of left ventricular reverse remodeling or systolic function had more severe systolic dyssynchrony. However, further studies are needed to examine the clinical utility of these parameters when applied to the standardized anatomic or functional endpoints. Optimization of atrioventricular and interventricular pacing intervals may also reduce the number of nonresponders, though newer methods, especially interventricular pacing intervals, are still under clinical investigation. CONCLUSION: With the adjunctive use of imaging technology, physicians are able to characterize the response to CRT objectively, and cardiac imaging is an important clinical tool for determining more precisely the presence and degree of mechanical dyssynchrony.

Cardiac Pacing, Artificial↗

Comparison of the Bravo wireless and Digitrapper catheter-based pH monitoring systems for measuring esophageal acid exposure.

INTRODUCTION: We compared esophageal acid exposure data obtained during simultaneous esophageal pH studies using the Bravo wireless and the Slimline catheter-Mark III Digitrapper pH systems. METHODS: Twenty-five asymptomatic subjects underwent endoscopy with endoclip placement at the squamocolumnar junction (SCJ) and manometry to localize the lower esophageal sphincter (LES). A Bravo capsule was placed 6 cm above the SCJ and a Slimline catheter 5 cm above the LES. Relative positions were checked fluoroscopically. Synchronized pH data were compared by manual extraction into Excel spreadsheets. An in vivo pH reference was established with swallows of orange juice (pH 3.88). RESULTS: Median acid exposure time was greater with the Slimline compared to the Bravo system (Slimline, 3.4%; Bravo, 1.76%, p < 0.05) but electrode positions were similar. The dominant source of discrepancy between systems was an offset in recorded pH values around pH 4 as evidenced by the recorded values of the swallowed orange juice. Bench-top testing suggested that this offset was mainly attributable to the software designed to compensate for the difference in electrode recording characteristics between room and body temperature. After adjusting the pH data sets to accurately reflect actual orange juice pH, acid exposure between systems was similar (Slimline, 0.90%; Bravo, 1.15%). CONCLUSION: The Slimline system on average over-recorded esophageal acid exposure compared to the Bravo system largely because of a flawed software scheme for electrode thermal calibration. Accuracy of pH data sets from both systems can be improved by scrutiny for artifacts and use of an in vivo pH reference.

Acids↗

Bravo capsule placement in the gastric cardia: a novel method for analysis of proximal stomach acid environment.

BACKGROUND: Intragastric pH monitoring is currently done using catheter-based pH systems. This study assessed the feasibility of proximal intragastric pH recording with the Bravo wireless pH monitoring system using novel methodology. METHODS: Nine asymptomatic volunteers and 9 symptomatic patients were studied. One pH capsule was positioned under direct endoscopic visualization so that the device straddled the squamocolumnar junction (SCJ) with the attachment well positioned on squamous mucosa and the pH electrode 1.5-2 cm distal to the SCJ. A second capsule was placed 6 cm proximal to the SCJ. The signal from each capsule was recorded by a separate receiver synchronized for time. RESULTS: Successful placement and interpretable recording for >42 h from both pH capsules was achieved in 16 (88%) of 18 subjects. Data capture were 98.3% in the cardia and 97.7% in the esophagus. Two failures occurred due to premature capsule detachment (one esophageal and one gastric). The acid environment in the cardia was similar in asymptomatic controls and symptomatic patients and exhibited less meal-related buffering than is typical of more distal intragastric recordings. In addition, nadir gastric cardia pH was almost always less than nadir esophageal pH during reflux events. CONCLUSIONS: Twenty-four hour gastric cardia pH monitoring is feasible with the Bravo system and can be added to esophageal pH monitoring to assess concomitant cardia acidity. Instantaneous cardia pH defines the potential nadir esophageal pH during reflux events.

Cardia↗

Searching for potential drug targets in two-component and phosphorelay signal-transduction systems using three-dimensional cluster analysis.

Two-component and phosphorelay signal transduction systems are central components in the virulence and antimicrobial resistance responses of a number of bacterial and fungal pathogens; in some cases, these systems are essential for bacterial growth and viability. Herein, we analyze in detail the conserved surface residue clusters in the phosphotransferase domain of histidine kinases and the regulatory domain of response regulators by using complex structure-based three-dimensional cluster analysis. We also investigate the protein-protein interactions that these residue clusters participate in. The Spo0B-Spo0F complex structure was used as the reference structure, and the multiple aligned sequences of phosphotransferases and response regulators were paired correspondingly. The results show that a contiguous conserved residue cluster is formed around the active site, which crosses the interface of histidine kinases and response regulators. The conserved residue clusters of phosphotransferase and the regulatory domains are directly involved in the functional implementation of two-component signal transduction systems and are good targets for the development of novel antimicrobial agents.

Binding Sites↗

Trypanosomal TBP functions with the multisubunit transcription factor tSNAP to direct spliced-leader RNA gene expression.

Protein-coding genes of trypanosomes are mainly transcribed polycistronically and cleaved into functional mRNAs in a process that requires trans splicing of a capped 39-nucleotide RNA derived from a short transcript, the spliced-leader (SL) RNA. SL RNA genes are individually transcribed from the only identified trypanosome RNA polymerase II promoter. We have purified and characterized a sequence-specific SL RNA promoter-binding complex, tSNAP(c), from the pathogenic parasite Trypanosoma brucei, which induces robust transcriptional activity within the SL RNA gene. Two tSNAP(c) subunits resemble essential components of the metazoan transcription factor SNAP(c), which directs small nuclear RNA transcription. A third subunit is unrelated to any eukaryotic protein and identifies tSNAP(c) as a unique trypanosomal transcription factor. Intriguingly, the unusual trypanosome TATA-binding protein (TBP) tightly associates with tSNAPc and is essential for SL RNA gene transcription. These findings provide the first view of the architecture of a transcriptional complex that assembles at an RNA polymerase II-dependent gene promoter in a highly divergent eukaryote.

Amino Acid Sequence↗

D-galactose injured neurogenesis in the hippocampus of adult mice.

OBJECTIVES: We studied the effects of the reactive oxygen species (ROS) on neural progenitor cell proliferation and survival in the dentate gyrus (DG). METHODS: The adult mice were treated with D-galactose for 7 weeks to mimic natural aging in mice. The level of malondialdehyde (MDA) and the activities of antioxidant enzymes in the serum were detected. Neurodegeneration and neurogenesis in the hippocampus were explored using terminal deoxynucleotidyltransferase-mediated UTP nick-end labeling (TUNEL) to detect the dying cells and bromodeoxyuridine (BrdU) was used to label the newly born cells. RESULTS: After the treatment of D-galactose, the level of MDA increased and the activities of the antioxidant enzyme decreased in the serum. TUNEL-positive cells significantly increased in the DG, CA1 and CA3 subfields. The BrdU-labeled proliferating cells and surviving cells in the DG decreased significantly in number after D-galactose treatment. DISCUSSION: D-Galactose induced the impairment of neurogenesis in the DG, which is similar to natural aging in mice. ROS accumulation as a result of D-galactose may be related to the decrease of neurogenesis in the DG.

Animals↗

Dimensional stability of the alveolar ridge after implantation of a bioabsorbable bone graft substitute: a radiographic and histomorphometric study in rats.

This study evaluated reconstruction of the alveolar ridge after molar extraction in rats with bioabsorbable bone repair scaffolds. The material was prepared from the unsaturated polyester poly(propylene glycol-co-fumaric acid) (PPF), which may be cured in situ to form a porous scaffold. The intention is to use this material either as a stand-alone bone graft substitute or as an extender to autograft harvested from mandibular reconstruction sites. The bioactivity of the graft substitute was investigated in a rat residual ridge resorption model. PPF bone repair material was injected into the defect site, where it cross-linked in situ in the presence of a hydroxyapatite (HA) filler and effervescent agents. The PPF-based material develops porosity during an in situ cure by generating carbon dioxide during the effervescent reaction of citric acid and sodium bicarbonate. The incorporation of HA promotes osteoconduction within the bone repair scaffold. In this study, bioactivity of the porous scaffold was evaluated as a function of HA particle size (micrometer-sized vs nanometer-sized particles). The maxillary or mandibular molars on the right side were extracted from 96 adult Sprague-Dawley rats. A 2-mm round bur was used to create a uniform trench defect measuring 2 mm in diameter, 2 mm in depth, and 4 mm in length at each extraction site. The defect site was (1) treated with PPF bone repair material containing nanometer-sized HA, (2) treated with PPF material containing micrometer-sized HA, (3) treated with demineralized freeze-dried bone allograft, or (4) left untreated. Rats were sacrificed at 2, 4, 7, and 12 weeks postoperative. Resorption of the residual alveolar ridge was assessed by radiographic outcomes. Bone ingrowth through the defect site was measured by histomorphometric outcomes. Mandibular and maxillary ridge heights increased for all treatments used in this study. There were no clinical indications that addition of either of the PPF bone repair materials retarded hard- or soft-tissue healing of the extraction sites. Although not statistically significant, the mandibular defects treated with PPF containing nanometer-sized HA healed at a faster rate as determined by ridge height and new bone formation measurements when compared with the other treatments. These findings suggest the feasibility of using PPF bone graft substitutes for oral-maxillofacial applications.

Absorbable Implants↗