Search PubMed⌕ Search

Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 397 records · Page 22Linked to original sources

Building a protein interaction map: research in the post-genome era.

With the extensive amount of information generated by genome-wide sequencing, the entire set of gene products in an organism can now be predicted. The challenge of understanding the function of each gene in the genome has led to the development of many large-scale and high-throughput experimental techniques. Recently, two papers, Walhout et al.(1) and Uetz et al.,(2) have described studies that add a new functional dimension to research conducted on a genome-wide scale. These two groups have utilized the yeast two-hybrid system to identify interactions among the entire complement of proteins encoded by the Caenorhabditis elegans and the Saccharomyces cerevisiae genomes, respectively. Using a set of 29 genes that have been previously characterized, Walhout et al. demonstrated the feasibility and efficiency of this technique by building an interaction matrix among a large number of proteins. On an even larger scale, Uetz et al. conducted two-hybrid analyses using proteins that represent over 87% of the total gene products in yeast and identified interactions for about 15% of the total yeast proteins. BioEssays 22:503-506, 2000.

Animals↗

In vivo intermolecular double-quantum imaging on a clinical 1.5 T MR scanner.

A novel MRI method based on the intermolecular double-quantum coherence (DQC) for soft tissues is described. DQC images of human brain were obtained for the first time on a whole-body 1.5 T scanner. The combination of quantum and classical formalisms was used to characterize multiple-quantum coherences, and to aid in the design of a DQC imaging sequence. The theoretical analysis suggests that signals from the intermolecular DQCs have higher sensitivity than those from the zero-quantum coherence (ZQC) for human brain, and the sensitivity increases with increased field strength. The DQC signal may provide a new form of contrast for MRI.

Brain↗

Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-kappaB.

BACKGROUND: Response to neoadjuvant cisplatin-based chemotherapy has been used to predict overall response to chemoradiation therapy and to select patients with head and neck squamous cell carcinoma (HNSCC) for organ preservation therapy in NCI and VA cooperative group trials. However, different molecular determinants have been reported to contribute to sensitivity of cells to cisplatin and radiation, including glutathione (GSH), and activation of nuclear factor-kappaB (NF-kappaB), a transcription factor that regulates cytoprotective genes. We have reported that NF-kappaB is constitutively activated in HNSCC, but the relationship of NF-kappaB to GSH and to cisplatin and radiation sensitivity in HNSCC is unknown. METHODS: We examined human HNSCC lines to define the relationship of cisplatin and radiation sensitivity to intracellular GSH and NF-kappaB and determined whether HNSCC could be sensitized to these modalities by lowering the concentration of glutathione with L-buthionine sulfoximine or inhibiting activation of NF-kappaB by expression of a degradation-resistant mutant inhibitor-kappaBalpha. RESULTS: Cisplatin resistance did not predict radiation resistance in three HNSCC cell lines, UM-SCC-9, 11B, and, 38. Resistance to cisplatin correlated with intracellular GSH, and depletion of GSH by treatment with L-BSO sensitized UM-SCC-9 cells to cisplatin but not radiation. Conversely, radiation resistance was correlated with activation of NF-kappaB. Expression of a mutant Inhibitor-kappaB after gene transfer inhibited NF-kappaB and sensitized UM-SCC-9 cells to radiation but not cisplatin. CONCLUSIONS: GSH and transcription factor NF-alphaB can contribute independently to cisplatin and radiation sensitivity of human HNSCC. These results highlight the need to define molecular determinants of chemotherapy and radiation sensitivity for use in the selection of patients and as novel targets for therapy in future chemoradiation therapy trials for organ preservation in patients with HNSCC.

Base Sequence↗

New image contrast mechanisms in intermolecular double-quantum coherence human MR imaging.

We have developed a novel magnetic resonance imaging (MRI) method based on the intermolecular double-quantum coherence (DQC) in humans. Combined quantum mechanical and classical formalisms were used to characterize the signal and to aid in the design of a DQC imaging sequence with conventional or echoplanar acquisitions. Imaging contrast was evaluated in volunteers using a 1.5-T clinical scanner. The results demonstrated that the DQC images have contrasts fundamentally different from the conventional images based on single-quantum coherence (SQC). Both our theoretical analysis and experiments suggest that signals from DQCs have a higher signal-to-noise ratio than those from zero-quantum coherence (ZQC) for human brain imaging. The new contrast in DQC imaging may be useful for the detection of varying microstructures, potentially improving the detection of tumors without the need for contrast agents and providing a higher sensitivity and selectivity to magnetic susceptibility distributions in functional MRI brain studies.

Brain↗

External and Internal Instantiation of Abstract Information Facilitates Transfer in Insight Problem Solving.

Four studies were conducted to examine how instantiation of abstract statements facilitates solutions to insight problems. The first two experiments explored the effects of external instantiation (adding a concrete example to the abstract source information) on transfer. Providing an example along with the abstract source statement fostered transfer of analogous solutions. Moreover, adding a complete concrete instantiation to an abstract statement produced greater transfer than adding only specific items to illustrate the abstract terms. The second two experiments examined the effects of internal instantiation (encouraging learners to generate their own concrete examples of the abstract information) on transfer. This factor, too, facilitated problem solving. Generating examples to instantiate the abstract statement yielded even better transfer than simply informing participants of the relationship between the abstract statements and the target problems. These findings suggest that both external and internal instantiation facilitate transfer by promoting mental processes associated with implementing the source analogs. Copyright 2000 Academic Press.

Journal Article↗

Evidence for persistent expression of OX2 as a necessary component of prolonged renal allograft survival following portal vein immunization.

Following portal vein (pv) pretransplant immunization of C3H mice, there is an early (within 2 days) increase in expression of the molecule OX2 seen on host dendritic cells (DC), along with increased survival of C57BL/6 renal allografts transplanted within 24 h of pv immunization. In addition, there is a marked polarization in cytokine production from lymphocytes harvested from the transplanted animals, with preferential production of IL-4, IL-10, and TGFbeta on donor-specific restimulation in vitro, and decreased production of IL-2, IFN-gamma, and TNFalpha compared with non-pv-immunized control transplanted mice. Both the increased renal allograft survival and the altered cytokine production are abolished by infusion of anti-mouse OX2 monoclonal antibody (3B6), even when antibody infusion is begun as late as 10 days following transplantation. Quantitative PCR analysis independently shows that OX2 expression is increased in the spleen and liver of transplanted mice as late as 21 days following pv immunization. In vitro studies with an OX2:Fc immunoadhesion had suggested that immunosuppression induced by this soluble form of the OX2 molecule was dependent primarily upon an early (OX2-dependent) signal. This discrepancy between in vivo and in vitro data possibly reflects a role for OX2 in the in vivo recruitment of other (immunregulatory) cells. Consistent with this hypothesis, regardless of the time (posttransplantation) of in vivo infusion of anti-OX2 antibody, within 2 days we observed a decline in the functional activity of a previously characterized immunoregulatory gammadeltaTCR(+) cell population, which can be monitored by its ability to regulate cytokine production in vitro.

Animals↗

t(1) noise and sensitivity in pulsed field gradient experiments.

In this paper, a calculation routine based on product operator formalism and coherence pathway is presented, which describes t(1) noise and sensitivity in pulsed field gradient experiments. Several examples including the absolute value mode pulsed field gradient COSY, MQF-COSY, MQC, HMQC, and NOESY sequences are investigated to study the t(1) noise stemming from the phase errors of radiofrequency (RF) pulses and the sensitivity affected by RF pulse rotation angles. Our theoretical results indicate that the t(1) noises in P-type COSY, multiple-quantum-filtered (MQF)-COSY, and multiple-quantum coherence (MQC) are lower than those in the N-type corresponding experiments, while in HMQC and NOESY there is no difference in t(1) noise effects between P-type and N-type spectra. Meanwhile, from the calculations, we obtained the optimized RF pulse rotation angles in those sequences. In MQF-COSY, an increase in sensitivity of about 4(cos(2)θ sin(q-1)2θ)(2) - 1 (θ = arc cot can be achieved by using the optimized angles. In MQC, the increase is 2 cos(2)θ sin(q-1)2θ - 1 (θ = arc cot. MQF-COSY experiments are also carried out to support our corresponding theoretical results.

Magnetic Resonance Spectroscopy↗

A reliability test of standard-based quantitative PCR: exogenous vs endogenous standards.

The quantitative measurement of gene expression requires consistent and reliable standards. At least two categories of standards, endogenous and exogenous, are currently used for quantitative PCR. The reliability of these two methods, however, has not been carefully compared. We hypothesized that a reliable quantitative PCR assay would be able to detect known dilutions of a given single-stranded (ss-) cDNA. By measuring VEGF ss-cDNA copy numbers or signal ratios of GAPDH/VEGF in 10x and 100x diluted samples of two original ss-cDNA preparations, an exogenous recombinant DNA standard (a VEGF-mimic plasmid) and an endogenously expressed GAPDH standard were tested for their ability to detect dilution factors. Using the recombinant DNA standard, the dilution factor was detected as 10.3 and 135.0 in 10x and 100x diluted samples of the original CaSki cell ss-cDNA, respectively. The detected dilution factors were 12.3 and 226.2, respectively, in 10x and 100x diluted ss-cDNA from U-251 MG cells. On the other hand, with the endogenous GAPDH standard, the dilution factors were detected as 2.7 and 8.0 in the same 10x and 100x dilutions of the original U-251 MG cell ss-cDNA. Using the same endogenous GAPDH standard, the detected dilution factors were both 4.8 in 10x and 100x dilutions of the original CaSki cell ss-cDNA. It was also found that the number of endogenous copies of GAPDH mRNA was about 1000 times higher than VEGF. The high internal lockup ratio of GAPDH vs VEGF copy numbers and the requirement for additional primer pairs make the use of an abundant endogenous standard an unreliable choice in quantitative or semi-quantitative PCR. In contrast, exogenous standard-based quantitative PCR was shown to be an accurate and reliable method for the quantitation of gene expression.

Central Nervous System Neoplasms↗

Prolongation of cardiac allograft survival using dendritic cells treated with NF-kB decoy oligodeoxyribonucleotides.

Dendritic cells (DC) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness in vitro. The expression of costimulatory molecules (CD40, CD86, CD80) at the DC cell surface correlates with their capacity to induce or suppress immune responses. Expression of these molecules is associated with NF-kB-dependent transcription of their genes. DC tolerogenicity has been associated with impaired NF-kB-dependent transcription of costimulatory genes as well as NF-kB translocation to the nucleus. In this report, we demonstrate that double-stranded oligodeoxyribonucleotides containing binding sites for NF-kB (NF-kB ODN) are efficiently incorporated by bone marrow-derived DC and specifically inhibit NF-kB-dependent transcription of a reporter gene. Moreover, exposure of DC to the oligonucleotide decoys inhibited lipopolysaccharide (LPS)-induced nitric oxide production, a marker of DC maturation. Treatment of bone marrow-derived DC progenitors with NF-kB ODN selectively suppressed the cell-surface expression of costimulatory molecules without interfering with MHC class I or class II expression. Furthermore, NF-kB ODN DC induced allogeneic donor-specific hyporesponsiveness in mixed leukocyte cultures, and this was associated with inhibition of Th1-type cytokine production. Finally, infusion of NF-kB ODN-modified bone marrow-derived DC into allogeneic recipients prior to heart transplantation resulted in significant prolongation of allograft survival in the absence of immunosuppression. Specific interference with NF-kB and other transcriptional pathways involved in immune stimulation in DC using ODN decoy approaches could be one means to promote tolerance induction in organ transplantation.

Animals↗

Quantitation of intermolecular dipolar effects in NMR spectroscopy and high order MSE MR imaging.

An analytical expression for intermolecular dipolar effects was derived for the CRAZED sequence with an arbitrary flip angle of the second RF pulse and time-varying gradients. A combination of the demagnetizing field theory and product operator formalism was utilized in the derivation. It is demonstrated that the time-averaged, not instantaneous, orientation of the applied gradients determines the contributions of long-range intermolecular dipole effects. An imaging sequence to detect intermolecular dipolar effects was designed. The second- and third-order multiple spin echo (MSE) NMR signals of swine muscle were observed and were found to be in good agreement with the theoretical predictions. MSE images of a water phantom with nth orders (n = 2, - 3, - 4, and - 5) were also obtained, and their relative signal intensities and optimized TE values were elucidated and compared with the theoretical prediction.

Animals↗

Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells.

Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR alpha/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor a (RAR alpha) (including: PML-RAR alpha, PLZF-RAR alpha, NPM-RAR alpha, NuMA- RAR alpha or STAT5b-RAR alpha) as a result of chromosomal translocations, the RA signal pathway is disrupted and myeloid differentiation is arrested at the promyelocytic stage. Pharmacologic dosage of all-trans retinoic acid (ATRA) directly modulates PML-RAR alpha and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR alpha/RXR regulatory pathway and induces the transcriptional expression of downstream genes. Analysing gene expression profiles in APL cells before and after ATRA treatment represents a useful approach to identify genes whose functions are involved in this new cancer treatment. A chronologically well coordinated modulation of ATRA-regulated genes has thus been revealed which seems to constitute a balanced functional network underlying decreased cellular proliferation, initiation and progression of maturation, and maintenance of cell survival before terminal differentiation.

Antineoplastic Agents↗

Methodological study of cell separation with domestic immunomagnetic beads.

To establish the method of cell separation with domestic immuomagnetic beads, three methods were investigated. Direct method, SPA method and Biotin-Avidin method were applied to separate cell strain Hut-78 and CD4 positive cells. Separation rate of strain Hut-78 was more than 90% in direct method. Detachment rate with papain was over 95%. Cell activity was well retained. SPA method and Biotin-Avidin methods were also effective, but the direct method was superior to the other two techniques. Before separated by the direct method, CD4 positive cells constituted 46.4% +/- 6.4% of mononuclear cells (MNC), but in eliminated suspension there was only 6.2% +/- 2.3% CD4 positive cells left. In the separated part, 80.6% +/- 7.2% of the cells combined with the beads. It is concluded that the direct method in separating cells had high sensitivity and specificity.

CD4-Positive T-Lymphocytes↗

Correlative expression of glutathione S-transferase-pi and multidrug resistance associated protein in bladder transitional cell carcinoma.

In order to elucidate the mechanisms of multidrug resistance (MDR) in bladder cancer, the expression of glutathione S-transferase-pi (GST-pi) and multidrug resistance associated protein (MRP) in tissue samples resected from 44 patients and 6 normal bladder mucosa as control was detected by using immunohistochemical method, and the results were analyzed by computer-assisted image analyzing system (IAS) to achieve semi-quantitative data. In addition, correlation between the expression of both factors was studied. The results showed that the positive expression rate of GST-pi and MRP in bladder cancer was 72.7% (32/44) and 68.2% (30/44) respectively, significantly higher than those in normal bladder mucosa, being 16.7% and 33.3% respectively. The rate of GST-pi positive staining was increased correspondingly with tumor grade and stage elevated, being higher in recurrent tumors treated by chemotherapy, but not significantly (P > 0.05). There was no significant differences between the expression of MRP and tumors' behaviors and clinical characters. However, the results demonstrated that the correlation between the expression of both resistant factors was very evident (r = 0.695, P < 0.0025). It was suggested that the activation of GST-pi and MRP might occur during malignant transformation of normal mucosa, but tumors' differentiation and progression could not be the unique factors that influenced both overexpression. Chemotherapy might be another important reason. The correlation of both indicated that there was a common mechanism regulating their expression probably, which made them play a pivotal role in chemotherapy drug resistance of bladder cancers.

Adult↗

A new model of erythrocyte injury in rats with Xueyu syndrome and its application.

A new model of rats with Xueyu Syndrome which was characterized by erythrocyte injury was presented. Observation of morphology and functions of erythrocytes showed that this model could not only be used as a model in Xueyu Syndrome and Huoxuequyu treatment study, but also be used for screening of drugs with the effect of preventing and treating damage of red blood cells.

Animals↗

Automated in situ trace element analysis of silicate materials by laser ablation inductively coupled plasma mass spectrometry.

This paper describes the automated in situ trace element analysis of solid materials by laser ablation (LA) inductively coupled plasma mass spectrometry (ICP-MS). A compact computer-controlled solid state Nd:YAG Merchantek EO UV laser ablation (LA) system has been coupled with the high sensitivity VG PQII S ICP-MS. A two-directional communication was interfaced in-house between the ICP-MS and the LA via serial RS-232 port. Each LA-ICP-MS analysis at a defined point includes a 60 s pre-ablation delay, a 60 s ablation, and a 90 s flush delay. The execution of each defined time setting by LA was corresponding to the ICP-MS data acquisition allowing samples to be run in automated cycle sequences like solution auto-sampler ICP-MS analysis. Each analytical cycle consists of four standards, one control reference material, and 15 samples, and requires about 70 min. Data produced by Time Resolved Analysis (TRA) from ICP-MS were later reduced off-line by in-house written software. Twenty-two trace elements from four reference materials (NIST SRM 613, and fused glass chips of BCR-2, SY-4, and G-2) were determined by the automated LA-ICP-MS method. NIST SRM 610 or NIST SRM 613 was used as an external calibration standard, and Ca as an internal standard to correct for drift, differences in transport efficiency and sampling yield. Except for Zr and Hf in G-2, relative standard deviations for all other elements are less than 10%. Results compare well with the data reported from literature with average limits of detection from 1 ng x g(-1) to 455 ng x g(-1) and less than 100 ng x g(-1) for most trace elements.

Journal Article↗

An immune algorithm for resolution of multicomponent overlapping chromatograms.

A novel immune algorithm for resolution and quantitative determination of the components in overlapping chromatograms was proposed by imitating biological immune systems. The algorithm takes an overlapping chromatogram as its input and subtracts the chromatograms of standard samples from the input by iteration of a network. When the residual does not change, the network will converge and chromatographic information of the components in overlapping chromatogram will be obtained. Both simulated and experimental data sets were investigated by the method. Results showed that both resolved results and recoveries of quantitative determination are satisfactory. Comparing with conventional least-square method, the immune algorithm is fast in calculation.

Algorithms↗

Challenge from methacholine, natural rubber latex, or 4,4-diphenylmethane diisocyanate in workers with suspected sensitization affects exhaled nitric oxide [change in exhaled NO levels after allergen challenges].

OBJECTIVE: Nitric oxide (NO) levels in the exhaled air of asthmatic patients have been shown to be increased. This observation has also been reported in workers who are allergic to laboratory animals. To determine if a challenge test with natural rubber latex (NRL) or 4,4'-diphenylmethane diisocyanate (MDI) would also produce an increase of NO exhalation in sensitized patients, we carried out this study. METHODS: Nine subjects with suspected occupational asthma were exposed to MDI, and 18 took part in a challenge test with gloves powdered with NRL. Nineteen subjects underwent a challenge test with methacholine (MCh). Exhaled NO was measured by a modified chemiluminescence analyzer according to the European Respiratory Society guidelines. RESULTS: We found that there was a decrease in exhaled NO concentrations 16-18 h after MCh challenge testing and subsequent bronchodilation with salbutamol, in three subjects. Three of nine participants had a significant immediate bronchial obstruction after exposure to MDI, of those three, two had MDI-specific IgE antibodies. After 22 h, their levels of exhaled NO had increased > 10 parts per billion (ppb). Eight of the 18 subjects participating in the NRL challenge test displayed an NO concentration increase of at least 10 ppb after 22 h (seven had NRL-specific IgE antibodies). A significant decrease in the one-second forced expiratory volume (FEV1) was documented in four of those eight participants after NRL challenge. CONCLUSIONS: There was no clear relationship between bronchial response, substance-specific IgE antibodies and an increase in exhaled NO levels. However, there was a tendency for subjects with substance-specific IgE antibodies and bronchial reaction to develop an increase in exhaled NO concentration. Further studies are needed to determine if analysis of NO from the lower respiratory tract can become a useful non-invasive tool for detecting lower airway inflammatory response even before clinical symptoms occur.

Adolescent↗

Pseudorabies virus induces apoptosis in tissue culture cells.

The process of cell death as a result of exposure to pseudorabies virus (PRV) in cultured cells was examined and specific features characteristic of apoptosis were observed. At early times of infection, externalization of membrane phospholipid phophatidylserine was detected by flow cytometry analysis. During the infection process, caspase 3-like protease activity was induced and the activity increased in a time dependent manner. Cellular DNA degradation was demonstrated by agarose gel electrophoresis. Morphologic changes of the nucleus that included chromatin condensation and margination to the periphery of the nucleus were evident in electron microscopy analysis. These biochemical and morphologic changes demonstrated that, during PRV replication, the host cell was induced to undergo apoptosis.

Animals↗