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Biomedical subjects

Qing Zhang

Publications and source records attributed to Qing Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2005

Microfluidic device as a new platform for immunofluorescent detection of viruses.

A bead-based microfluidic device was developed and demonstrated to achieve rapid and sensitive enzyme-linked immunosorbent assay (ELISA) with quantum dots as the labeling fluorophore for virus detection. In comparison to standard ELISA performed on the same virus, the minimal detectable concentration of the target virus was improved from 360 to 22 ng mL-1, the detection time was shortened from >3.25 h to <30 min, and the amount of antibody consumed was reduced by a factor of 14.3.

Animals↗
PubMed2005

Fabrication of poly(dimethylsiloxane) microfluidic system based on masters directly printed with an office laser printer.

Applications of poly(dimethylsiloxane) (PDMS)-based microfluidic systems are more popular nowadays. Previous fabrication methods of the masters for PDMS microchannels require complicated steps and/or special device. In this paper, we demonstrated that the toner printed on the transparency film with the office laser printer (1200 dpi) can be used as the positive relief of the masters. The transparency film was printed in two steps in order to obtain the same printing quality for the crossed lines. With the laser-printed master, the depth of the fabricated PDMS microchannels was ca. 10 microm and the smallest width was ca. 60 microm. Surface characteristics of the PDMS/PDMS microchannels were performed with SEM. Their electrokinetic properties were investigated by the aids of the measurement of electroosmotic flow (EOF) and the Ohm's curve. Using the PDMS/PDMS microchip CE systems, electroactive biological molecules and non-electroactive inorganic ions were well separated, respectively. This simple approach could make it easy to carry out the studies of PDMS microfluidic systems in more general labs without special devices.

Dimethylpolysiloxanes↗
PubMed2005

The intracellular domain of CD44 promotes the fusion of macrophages.

Macrophages seed all tissues in which they have the ability, in specific and rare instances, to fuse with themselves and to differentiate into osteoclasts in bone or into giant cells in chronic inflammatory reactions. Although these cells play a central role in osteoporosis and in foreign body rejection, respectively, the molecular mechanism used by macrophages to fuse remains poorly understood. Macrophages might also fuse with somatic and tumor cells to promote tissue repair and metastasis, respectively. We reported that CD44 expression is highly induced in macrophages at the onset of fusion in which it plays a role. We report now that the intracellular domain of CD44 (CD44ICD) is cleaved in macrophages undergoing fusion and that presenilin inhibitors prevent the release of CD44ICD and fusion. We also show that CD44ICD promotes the fusion of tissue macrophages and bone marrow-derived macrophages. Finally, we report that CD44ICD is localized in the nucleus of macrophages in which it promotes the activation of NF-kappaB. These observations open avenues to study the role of CD44ICD in blood cells and tumors.

Animals↗
PubMed2005

Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy.

BACKGROUND: In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. METHODS AND RESULTS: Patients (n=141) with advanced heart failure (mean+/-SD age, 64+/-11 years; 73% men) who received CRT were followed up for a mean (+/-SD) of 695+/-491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of > or =9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank chi2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank chi2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank chi2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (beta=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (beta=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event. CONCLUSIONS: A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.

Aged↗
PubMed2005

Effects of cardiac resynchronization therapy on incidence of atrial fibrillation in patients with poor left ventricular systolic function.

Although the beneficial role of cardiac resynchronization therapy (CRT) in selected patients with heart failure is well proven, its effect on the incidence of atrial fibrillation (AF) is unclear. The present study compared the incidence of AF in 36 consecutive patients with chronic heart failure receiving CRT with its incidence in controls matched for age, gender, and left ventricular ejection fraction but not receiving CRT. The findings suggest that patients with CRT had a significantly lower incidence of AF than controls. Further studies to establish the role of CRT in preventing AF and its mechanisms are warranted.

Aged↗
PubMed2005

The complete genome sequence of Mycobacterium avium subspecies paratuberculosis.

We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease.

Animals↗
PubMed2005

GM1 ganglioside prevented the decline of hippocampal neurogenesis associated with D-galactose.

Hippocampal neurogenesis is thought to play a functional role in hippocampal-dependent learning and memory. The neurogenic capability of the hippocampus declines with age and may be associated with a decline in cognitive function. In the present study, an established model of ageing in mice was used to test the protective effects of GM1 ganglioside on hippocampal neurogenesis. This model uses D-galactose treatment to cause neuronal injury and reduced neurogenesis. GM1 significantly increased the proliferation, long-term survival and neuronal differentiation of hippocampal progenitors that had been injured with D-galactose. This study demonstrates that GM1 can protect hippocampal neurogenesis from D-galactose injury. Therefore, GM1 may protect neurogenesis in the ageing brain.

Analysis of Variance↗
PubMed2005

[Allograft replacement in management of giant cell tumor of bone: a report of 77 cases].

OBJECTIVE: To evaluate the functional outcome and the complications of allograft replacement in management of giant cell tumors of bone. METHODS: Seventy-seven patients who underwent bone tumor resection and massive allograft reconstruction of bone defects between 1992 and 2002 were evaluated. The length of the resected part ranged from 5 to 11 centimeters. Fresh-frozen allografts were employed as osteoarticular grafts (n = 47), hemi-condylar (n = 12), massive (n = 14) or allograft-prosthesis composite (n = 4). Most of the lesions located in proximal and distal femur, proximal tibia and humerus. The oncological parameters that were evaluated including survival of the patient, local recurrence, and metastasis. The radiographic parameters included time to union, stability of the joint, fracture of the allograft. Mankin evaluation system was used to assess functional outcome. RESULTS: At a median of 35 months (range from 12 to 135 months) after the operation, 76 of the patients in the study group were free of disease, and one had died of disease. Eleven (14.1%) patients had local recurrence and 12 (15.4%) nonunion. Late complications included 5 (6.4%) fractures of the allograft and 5 (6.4%) infections of the graft. Instability of the joint in the form of subluxation was noted in 5 (6.4%) patients. One extremity were amputated due to local recurrence. On the basis of Mankin functional evaluation, the total satisfied rate was 83.2 percent. Osteoarticular graft got the highest score (91.5%) and hemi-condylar got the lowest (66.6%). Massive grafts and composite were at the middle (ranges from 71.4% to 75%). CONCLUSION: Allografts offer many types of reconstruction for bony defects after tumor resection. The functional results are comparable to other methods of reconstruction, and once incorporated by the host, offer the advantage of longevity. It is also a method with high complication, and decreasing the complications could improve the functional score. Less resection could get better reconstruction and better function, less margin resulted at the same time. The risk of recurrence increases when less surgical margin achieves. The main end-result-influencing factor is local recurrence.

Adolescent↗
PubMed2005

Electrochemically deposited chitosan hydrogel for horseradish peroxidase immobilization through gold nanoparticles self-assembly.

A new strategy for immobilization of horseradish peroxidase (HRP) has been presented by self-assembling gold nanoparticles on chitosan hydrogel modified Au electrode. From a mildly acidic chitosan solution, a chitosan film is electrochemically deposited on Au electrode surface via a negative voltage bias. This process is accompanied by the hydrogen evolution reaction, and the released hydrogen gas made the deposited chitosan film with porous structure, which facilitates the assembly of gold nanoparticles and HRP. The resulting substrates were characterized by atomic force microscopy (AFM) and electrochemical impedance spectroscopy (EIS). The immobilized HRP displayed an excellent catalytic property to the reduction of H2O2 in the presence of methylene blue mediator. The resulting biosensor (HRP-modified electrode) showed a wide dynamic range of 8.0 microM-15 mM H2O2, and the linear ranges were 8.0 microM-0.12 mM and 0.50-12 mM, with a detection limit of 2.4 microM estimated at a signal-to-noise ratio of 3. Moreover, the biosensor remained about 85% of its original sensitivity after four weeks' storage.

Animals↗
PubMed2005

Interfacial friction of surfaces grafted with one- and two-component self-assembled monolayers.

We present a quantitative study of the nanoscale frictional properties of one-component (pure) and two-component (mixed) alkylsilane self-assembled monolayers (SAMs). The load and velocity dependence of the friction force was measured in air and ethanol using lateral force microscopy (LFM). It was observed that for SAMs with well-ordered structure (pure SAMs and mixed SAMs composed of two long chain molecules) friction depends nonlinearly on load, at low loads, both in air and in ethanol. These observations are consistent with the low-load contact area predictions of the Johnson-Kendall-Roberts (JKR) theory, indicating that for well-ordered SAMs friction force is proportional to contact area and that the true contact area is determined by elastic deformation of the SAM by the LFM probe. In ambient air, the magnitude of the friction force measured using mixed SAMs is found to be similar to that obtained using pure SAMs at the same external load. Changing the medium to ethanol, however, leads to dramatically lower friction in the mixed SAMs. An analysis of the friction data using a thermally activated Eyring model that takes into account the monolayer viscoelasticity suggests that the better friction properties of the mixed SAMs are a consequence of greater disorder and higher molecular mobility in the outer layer/canopy. These findings indicate that multi-tiered SAM coatings comprising a highly ordered underlayer and a disordered, mobile canopy can provide the basis for low-friction coatings for small mechanical systems.

Friction↗
PubMed2005

Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas.

Indolent non-Hodgkin lymphomas are characterized by a prolonged phase that is typically followed by a clinical progression associated with an accelerated clinical course and short survival time. Previous studies have not identified a consistent cytogenetic or molecular abnormality associated with transformation. The development of a transformed phenotype, evolving from the original low-grade component, most likely depends on multiple genetic events, including the activation of synergistic dominant oncogenes and a loss of tumor suppressor gene functions. Complex karyotypes and relatively bad chromosome morphology are typical of transformed non-Hodgkin lymphomas, rendering complete cytogenetic analysis difficult. Here, we report the use of transformed non-Hodgkin lymphoma cell lines and primary samples to identify the involvement of the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) gene that maps at chromosome 12q24 in transformed non-Hodgkin lymphomas. We also show that down-regulation of SMRT in the immortalized "Weinberg's model" cell lines induces transformation of the cells. Assessment of cDNA array profiles should further help us to design a working model for SMRT involvement in non-Hodgkin lymphoma transformation as a novel, nonclassical tumor suppressor.

Apoptosis↗
PubMed2005

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.

Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.

Computer Simulation↗
PubMed2005

Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: roles of anoikis.

Anti-GD2 ganglioside antibodies could be a promising, novel therapeutic approach to the eradication of human small cell lung cancers, as anti-GD2 monoclonal antibodies (mAbs) induced apoptosis of small cell lung cancer cells in culture. In this study, we analyzed the mechanisms for the apoptosis of these cells by anti-GD2 mAbs and elucidated the mechanisms by which apoptosis signals were transduced via reduction in the phosphorylation levels of focal adhesion kinase (FAK) and the activation of a MAPK family member, p38, upon the antibody binding. Knock down of FAK resulted in apoptosis and p38 activation. The inhibition of p38 activity blocked antibody-induced apoptosis, indicating that p38 is involved in this process. Immunoprecipitation-immunoblotting analysis of immune precipitates with anti-FAK or anti-integrin antibodies using an anti-GD2 mAb revealed that GD2 could be precipitated with integrin and/or FAK. These results suggested that GD2, integrin, and FAK form a huge molecular complex across the plasma membrane. Taken together with the fact that GD2+ cells showed marked detachment from the plate during apoptosis, GD2+ small cell lung cancer cells seemed to undergo anoikis through the conformational changes of integrin molecules and subsequent FAK dephosphorylation.

Anoikis↗
PubMed2005

Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1.

BACKGROUND: During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. RESULTS: By using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs) expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 +/- 31.63) was higher than that of the undifferentiated THP-1 cells (205.1 +/- 19.25). There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively. CONCLUSION: The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1 cells. The matured monocytes / macrophages, via their high expression of CD147, may play an important role in promoting the tissue repair or tissue damage during their inflammatory response.

Basigin↗
PubMed2005

A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging.

OBJECTIVES: This study was designed to investigate if tissue synchronization imaging (TSI) is useful to identify regional wall delay and predict left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). BACKGROUND: Echocardiographic assessment of systolic asynchrony is helpful to predict a positive response to CRT. Tissue synchronization imaging is a new imaging technique that allows quick evaluation of regional systolic delay. METHODS: Tissue synchronization imaging was performed in 56 heart failure patients at baseline and three months after CRT. Regional wall delay was identified on TSI images and the time to regional peak systolic velocity (Ts) in LV was measured by the six-basal-six-mid-segmental model. Eight TSI parameters of systolic asynchrony were computed when Ts was measured in ejection phase or also included postsystolic shortening. RESULTS: Severe lateral wall delay occurred in 17 patients, which predicted LV reverse remodeling (chi-square = 8.13, p = 0.004). Among the eight quantitative parameters of asynchrony, the predictive values were higher for parameters that measured Ts in ejection phase than in postsystolic shortening. The standard deviation of Ts of 12 LV segments in ejection phase (Ts-SD-12-ejection) was most powerful to predict reverse remodeling (r = -0.61, p < 0.001) and gain in ejection fraction (r = 0.53, p < 0.001). The area of the receiver-operating characteristic (ROC) curve was the largest for Ts-SD-12-ejection (0.90, p < 0.001), with a sensitivity of 87% and specificity of 81% at a cutoff of 34.4 ms. The combination of lateral wall delay with Ts-SD-12-ejection gave a sensitivity and specificity of 82% and 87%. CONCLUSIONS: Tissue synchronization imaging allows quick evaluation of regional wall delay, and combined with Ts-SD-12-ejection provides a reliable way of predicting reverse remodeling after CRT.

Aged↗
PubMed2005

The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications.

BACKGROUND: The large amount of data that are currently produced in the biological sciences can no longer be explored and visualized efficiently with traditional, specialized software. Instead, new capabilities are needed that offer flexibility, rapid application development and deployment as standalone applications or available through the Web. RESULTS: We describe a new software toolkit--the Molecular Biology Toolkit (MBT; http://mbt.sdsc.edu)--that enables fast development of applications for protein analysis and visualization. The toolkit is written in Java, thus offering platform-independence and Internet delivery capabilities. Several applications of the toolkit are introduced to illustrate the functionality that can be achieved. CONCLUSIONS: The MBT provides a well-organized assortment of core classes that provide a uniform data model for the description of biological structures and automate most common tasks associated with the development of applications in the molecular sciences (data loading, derivation of typical structural information, visualization of sequence and standard structural entities).

Algorithms↗