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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 181 records · Page 10Linked to original sources

Combined effect of all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia cells in vitro and in vivo.

All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. To evaluate this possibility, this study examined the effect of As(2)O(3) on tRA-induced differentiation and, conversely, the effect of tRA on As(2)O(3)-induced apoptosis. As(2)O(3) at subapoptotic concentrations (0.5 microM) decreased tRA-induced differentiation in NB4 cells but synergized with atRA to induce differentiation in tRA-resistant NB4 subclones MR-2 and R4 cells as measured by nitroblue tetrazolium reduction and tRA-inducible genes (TTGII, RARbeta, RIG-E). tRA cleaved PML-RARalpha into distinct fragments in NB4 but not in tRA-resistant MR-2 or R4 cells, whereas As(2)O(3) completely degraded PML-RARalpha in all 3 cell lines. As(2)O(3)-induced apoptosis was decreased by tRA pretreatment of NB4 cells but not of R4 cells and was associated with a strong induction of Bfl-1/A1 expression, a Bcl-2 protein family member. Severe combined immunodeficient mice bearing NB4 cells showed an additive survival effect after sequential treatment, but a toxic effect was observed after simultaneous treatment with tRA and As(2)O(3). These data suggest that combined As(2)O(3) and tRA treatment may be more effective than single agents in tRA-resistant patients. Although in vitro data do not always translate to in vivo response, toxicity and potential drug antagonism may be diminished by decreasing the concentration of As(2)O(3) when given at the same time with therapeutic levels of tRA.

Animals↗

fMRI of auditory stimulation with intermolecular double-quantum coherences (iDQCs) at 1.5T.

An intermolecular double-quantum coherence (iDQC) imaging technique was used to study auditory activation in the human brain at 1.5T with a dual temporal lobe surface phased array coil and a quadrature head coil. Preliminary results demonstrate that it is feasible to obtain auditory activation maps using iDQC imaging at 1.5T, both in individual subjects using the surface coil array and with multisubject averaging of data using the head coil. The most robust activation map was obtained when a spin-echo (SE) acquisition was combined with an iDQC excitation. Since SE with conventional single quantum coherence (SQC) and similar parameters showed much reduced activation in spite of its higher signal-to-noise ratio (SNR), it was determined that activation resulting from the SE-iDQC acquisition almost entirely originates from iDQCs. In addition, the fact that the robust activation was obtained using signals at an evolution time more sensitive to changes in magnetic susceptibilities also suggests the sensitivity of iDQCs to the BOLD effect upon activation. iDQCs provide a novel MRI method which is potentially more sensitive to the BOLD effect traditionally measured with SQC. Magn Reson Med 45:356-364, 2001.

Acoustic Stimulation↗

Clay-enhanced DNA separation in low-molecular-weight poly(N,N-dimethylacrylamide) solution by capillary electrophoresis.

The effect of the separation medium in capillary electrophoresis consisting of a low-molecular-mass poly(N,N-dimethylacrylamide) (PDMA) solution on the DNA separation by adding a small amount of montmorillonite clay into the polymer matrix is presented. On the separation of the pBR322/HaeIII digest, both the resolution and the efficiency were increased by adding 2.5-5.0 x 10(-5) g/mL clay into the 5% w/v PDMA with a molecular mass of only 100 K. Moreover, there was no increase in the migration time of DNA fragments. Similar results were observed by using a C-terminated pGEM-3Zf(+) sequencing DNA sample in a sequencing buffer. Experimental data also showed that the addition of clay increased the viscosity of the polymer solution. We attribute this effect to the structural change of the polymer matrix caused by the exfoliated clay sheets, whereby the thin clay sheets function like a "dynamic cross-linking plate" for the PDMA chains and effectively increase the apparent molecular mass of PDMA.

Acrylamides↗

Chemically L-prolinamide-modified monolithic silica column for enantiomeric separation of dansyl amino acids and hydroxy acids by capillary electrochromatography and mu-high performance liquid chromatography.

A silica-based chiral monolithic column prepared by sol-gel process and chemical modification of chiral selector was used for enantioseparation of dansyl amino acids and hydroxy acids by capillary electrochromatography (CEC) and mu-high-performance liquid chromatography (mu-HPLC). L-Prolinamide was modified as a chiral selector. The chiral stationary phase (CSP), the chiral complex of Cu(II) with L-prolinamide, provides an anodic electroosmotic flow (EOF) in CEC. The EOF was found to be dependent on applied electric field strength, the pH, and the composition of mobile phases. Scanning electron micrograph showed that monolithic columns have the morphology of continuous skeleton and large through-pore. D-Enantiomers migrated before L-enantiomers except for dansyl-(Dns)-DL-Ser. The separation efficiencies of up to 17600 (D) and 13,200 plates m(-1) (L) were achieved for the separation of DL-indole-3-lactic acid.

Acetonitriles↗

Survey of the distribution of red tide toxins (okadaic acid and dinophytoxin-1) in the Dalian Bay sea area of China by micellar electrokinetic capillary chromatography.

Two kinds of diarrhoetic shellfish toxins, okadaic acid (OA) and dinophytoxin-1 (DTX-1) were determined by micellar electrokinetic capillary chromatography (MEKC) with ultraviolet detection. A detection limit of 3.25 microg/mL for both of them was achieved. The UV absorbance of these toxins measured at 200 nm showed good linearity in the range of 6.25-200 microg/mL with R = 0.992 for OA and 0.997 for DTX-1. Three kinds of shellfish (Chlamys farreri, Mytilus edulis and Ruditaps philippinarum) collected from eight locations (sampling in the intertidal zone) along the Dalian Bay sea area of China were surveyed in February and May of 2000. Results indicated that three kinds of shellfish were contaminated by OA and DTX-1. Based on per gram of hepatopancreas in February, the contamination contents ranged from 0 to 1.26 microg for OA and from 0 to 1.82 microg for DTX-1, and in May, the contents ranged from 0 to 1.45 microg for OA and 0 to 2.56 microg for DTX-1. Among the eight locations, Hei Shi Jiao and Long Wang Tang were the most contaminated areas. Of the three kinds of shellfish, Mytilus edulis was the most significant species in accumulating OA and DTX-1.

Animals↗

Interaction between 18-crown-6-tetracarboxylic acid and positional substituents of enantiomers and simultaneous separation of positional enantiomers of methyl-DL-tryptophans by capillary electrophoresis.

18-Crown-6-tetracarboxylic acid (18C6H4) is a chiral selector with high selectivity for the enantioseparation of solutes bearing the primary amine function. This work presents the simultaneous separation of positional enantiomers of methyl-DL-tryptophans by using 18C6H4 as an additive to the background electrolyte. Separation conditions such as pH, the concentration of 18C6H4, and the applied voltages have critical inference on the simultaneous separation. The addition of cyclodextrins as anionic surfactants to the background electrolyte did not improve the separation. The selector-selectand interactions between 18C6H4 and the positional enantiomers have been investigated. It was observed that both the position and type of substituents contribute to the enantioselectivity. The migration order and resolution depended on the distance from the substituents to the asymmetric carbon of the enantiomers.

Crown Ethers↗

Respiratory diseases caused by occupational exposure to 1,5-naphthalene-diisocyanate (NDI): Results of workplace-related challenge tests and antibody analyses.

BACKGROUND: 1,5-naphthalene-diisocyanate (NDI) is an aromatic diisocyanate with a very low vapor pressure which is mainly used in the automotive industry. METHODS: In the present study we described five cases with workplace-related asthma and one case with extrinsic allergic alveolitis associated with pulmonary hemorrhage after NDI exposure. RESULTS: Corresponding to case histories, extrinsic alveolitis on asthmatic reactions in three subjects and a rhinitis reaction in one patient could be reproduced by inhalative challenge tests to NDI at a concentration of 10 ppb. Preliminary IgE and IgG antibody analyses in patients' sera did not produce significantly positive results. CONCLUSIONS: According to the outcome of our tests and in comparison with several other studies, we conclude that NDI should be classified as potent airway-sensitizing substance. Improved workplace conditions and decrease in threshold limit values should therefore be recommended.

Adult↗

CD200 immunoadhesin suppresses collagen-induced arthritis in mice.

DBA/1 mice immunized with 100 microg bovine collagen type II emulsified in Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18 days, develop profound arthritis (>50% of animals) by 30 days postinjection. The molecule CD200 (previously called OX2), associated with, among others, follicular dendritic cells, is implicated in delivery of immunosuppressive signals to the immune system, and an immunoadhesin in which the extracellular domains of CD200 were linked to a mouse IgG2a Fc region has been shown to promote renal allograft survival. DBA/1 mice receiving 15 microg/mouse CD200Fc at 3-day intervals following immunization with collagen did not develop arthritis in this model. Lymphocytes taken from CD200Fc-treated, collagen-immunized mice produced significantly lower levels of TNFalpha and IFN-gamma in culture supernatants after restimulation in vitro with collagen, in contrast to cells taken from control mice treated with PBS or normal mouse Ig. Serum from CD200Fc-treated mice contained less anti-collagen IgG (approximately 50% reduction), with relatively more IgG2b and IgG3, and lower levels of TNFalpha and IFN-gamma, than control mice. These data indicate that this immunoadhesin may have a potent role to play in the regulation of autoimmune disorders.

Animals↗

Optical recording of the neuronal activity in the brainstem-spinal cord: application of a voltage-sensitive dye.

Although there are several limitations, optical recording techniques are superior to multi-electrode mapping methods, as it is possible to record at large number of points in a small area without destroying the tissue and possible to know relative changes of membrane potentials. Optical recording techniques using voltage-sensitive dyes will be more importantly applied in the study of central respiratory control (e.g., mechanisms of respiratory rhythm generation) in the near future.

Animals↗

Application of CD45/SSC gating multiparameter flow cytometry in the classification of acute leukemia--an analysis of 139 cases.

In order to study the significance of flow cytometry immunophenotyping in the diagnosis of acute leukemia, CD45/SSC gating multiparameter flow cytometry (FCM) was utilized to analyze the immunophenotypes of 139 cases of acute leukemia. 139 cases of acute leukemia were enrolled in our hospital from April 1998 to April 2000. Morphological analysis and FCM immunophenotypic tests were conducted on all cases. Our results showed that CD45/SSC gating multiparameter flow cytometry immunophenotyping could reflect the origin of leukemic cells specifically. It is one of the important methods for the diagnosis of ALL, AML, and HAL. CD45/SSC gating multiparameter FCM analysis is a good technique for immunophenotyping. FCM immunophenotypic analysis can help improve the diagnosis and classification of acute leukemia, and extend the use of FCM in clinical practice.

Adolescent↗

Construction and in vitro expression of Streptococcus mutans surface protein encoding DNA vaccine.

DNA vaccine plasmids were constructed that encoded two highly-conservative regions of a surface protein, PAc, from the human major cariogenic bacterium, Streptococcus mutans. Antigen expression was evaluated in vitro by immunohistochemical analysis of human endothelial cells following cationic liposome-mediated transient transfection with recombinant plasmid. The results of this study provided a basis for further testing of these recombinant plasmids in primates and for efficacy testing of dental caries DNA vaccines in human volunteers in future.

Antibodies, Bacterial↗

Clinical study on the treatment of 325 cases of atrioventricular node reentrant tachycardia by radiofrequency catheter ablation.

In order to improve the efficacy of modified inferior method or middle method of radiofrequency catheter ablation (RFCA) in the treatment of atrioventricular node reentrant tachycardia (AVNRT), the clinical data of 325 cases of AVNRT from March 1992 to Feb. 2000 being subjected to the treatment of RFCA were retrospectively analyzed. The results showed that the successful rate was increased and recurrence was decreased year by year. In the recent 4 years the effective rate was up to 100%. The complication of three grade of AVB occurred in 3% and recurrent rate in 9.1% before March 1996, but both of them were zero in the last 3 years. The time of RFCA procedure and X-ray exposure was significantly reduced. It was concluded that ablating more than 3 targets by modified inferior method or middle method with energy titrating and strict endpoint was the crux of obtaining satisfactory therapeutic effects and preventing recurrence.

Adolescent↗

Expression of multidrug-associated protein, P-glycoprotein, P53 and Bcl-2 proteins in bladder cancer and clinical implication.

The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug-associated protein (MRP), P-glycoprotein (P-gp), P53 and Bcl-2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P-gp, P53 and Bcl-2 was 52.5%, 57.5%, 47.5% and 62.5% respectively. The positive rate of MRP, P-gp, P53 and Bcl-2 in the grade I, II and III of tumors was 46.3%, 38.5%, 38.5%, 23.1%; 52.9%, 39.8%, 47.1%, 76.4%; 60.0%, 80.0%, 60.0%, 90.0% respectively. The positive rate of MRP, P-gp, P53 and Bcl-2 in 24 primary tumor specimens was 37.5%, 41.7%, 33.3%, 45.8% and that in 16 cases in recurrent specimens receiving chemotherapy 75.0%, 81.3%, 68.8%, 87.5% respectively. It was suggested the positive rate of MRP, P-gp, P53 and Bcl-2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased (P < 0.05). The expression of MRP, P-gp, P53 and Bcl-2 proteins might be the important factors for chemotherapy failure.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The possible role and application of WT1 in human leukemia.

WT1, a tumor suppressor gene responsible for the development of childhood kidney tumors, is now also thought to be involved in the occurrence of human leukemia. First, evidence has shown that WT1 functions during hematopoiesis and regulates the proliferation and differentiation of blood cells. Second, specific expression patterns of this gene correlate with the malignant phenotype of leukemia compared with the physiological situation. Third, mutations of WT1 can be detected, though not frequently, in human leukemia but not in normal hematopoietic cells. Thus, a possible role of WT1 in human leukemogenesis has been proposed. Because the expression of this gene is relatively high during the so-called myelodysplastic stages and in all subtypes of human leukemia compared with normal blood cells, the notion has been raised that WT1 can be used as a "panleukemic marker" for the diagnosis of leukemia at the molecular level. The expression level of WT1 may have significance in predicting prognosis and monitoring relapse. Moreover, with a deeper understanding of its role in leukemogenesis, WT1 may serve as a target molecule in the strategy of gene therapy for leukemia.

Cell Transformation, Neoplastic↗

Inhibition of apoptosis by primary isolates of herpes simplex virus.

HSV-1 inhibits apoptosis of the infected cell, presumably to increase viral yield. Weaker anti-apoptotic activity was previously reported in laboratory-adapted HSV-2, but not in two low-passage clinical HSV-2 isolates, suggesting that the anti-apoptotic effect might result from adaptation to laboratory growth. We therefore assembled a large panel of clinical strains of HSV-1 and HSV-2. Clinical and laboratory strains of HSV-1 strongly inhibited apoptosis of Jurkat cells, as determined by morphologic change or caspase activation, while clinical HSV-2 strains showed no inhibitory activity in Jurkat cells. These findings suggest fundamental differences between HSV-1 and HSV-2 in their manipulation of host cell apoptosis.

Animals↗

Replication competition between lactate dehydrogenase-elevating virus quasispecies in mice. Implications for quasispecies selection and evolution.

The common quasispecies of lactate dehydrogenase-elevating virus (LDV), LDV-P and LDV-vx, are highly resistant to the humoral host immune response because the single neutralization epitope on the ectodomain of the primary envelope glycoprotein, VP-3P, carries three large N-glycans. Two laboratory mutants, LDV-C and LDV-v, have lost two of the N-glycans on the VP-3P ectodomain, thereby gaining neuropathogenicity for AKR/C58 mice but at the same time, becoming susceptible to the humoral immune response of the host. In attempts to further assess the origins and evolution of these LDVs we have determined their competitiveness by monitoring their fate in mixed infections of wild type, SCID, nude, and cyclophosphamide-treated mice by reverse transcription/polymerase chain reaction assays that distinguish between them. In mixed infections with LDV-P and LDV-vx, LDV-C and LDV-v became rapidly lost even when present initially in large excess over the former. In mixed infections of mice unable to generate neutralizing antibodies, LDV-C and LDV-v also became replaced by LDV-P and LDV-vx as predominant quasispecies but more slowly than in immunocompetent mice. The results indicate that the humoral immune response plays an important role in the displacement of LDV-C and LDV-v by LDV-P and LDV-vx but that in addition, LDV-C and LDV-v possess an impaired ability to compete with LDV-P and LDV-vx in the productive infection of the subpopulation of macrophages that represents the host for all these LDVs. In addition, LDV-v outcompeted LDV-C in mixed infections and the same was the case for neutralization escape mutants of LDV-v and LDV-C which had regained all three N-glycosylation sites on the VP-3P ectodomain. Thus a hierarchy exists in replication fitness: LDV-P/LDV-vx>LDV-v>LDV-C, which is unrelated to the number of N-glycans on the VP-3P ectodomain. The implications of the results in relation to the evolution and selection of the LDV-quasispecies is discussed. LDV-P and LDV-vx are genetically highly stable and thus seem to have achieved evolutionary stasis with optimum ability to establish viremic persistent infections of mice that are unimpeded by the host immune responses.

Amino Acid Sequence↗

Conformational disorder of proteins assessed by real-space molecular dynamics refinement.

Motion is critical to the function of many proteins, but much more difficult to study than structure. Due to lack of easy alternatives, although there are inherent limitations, there have been several prior attempts to extract some information from the Bragg scattering in conventional diffraction patterns. Bragg diffraction reflects only a small proportion of a protein's motion and disorder, so fitted values likely underestimate reality. However, this work shows that the fitted estimates should be even smaller, because current methods of refinement over-fit the Bragg diffraction, leading to a component of the disorder that is not based on any experimental data, and could be characterized as a guess. Real-space refinement is less susceptible than other methods, but its application depends on the availability of very accurate experimental phases. A future challenge will be the collection of such data without resort to cryo-techniques, so that a physiologically relevant understanding can be achieved.

Amino Acid Sequence↗

The LDL receptor is the major pathway for beta-VLDL uptake by mouse peritoneal macrophages.

In order to determine the contribution of the low density lipoprotein receptor (LDL-R) to the removal of apoB-containing native lipoproteins by macrophages, we compared the uptake of beta-VLDL in peritoneal macrophages (MPM) from wild type mice and mice lacking the LDL-R. The d<1.006 g/ml lipoproteins obtained from apoE deficient mice fed a high fat diet were poorly degraded by macrophages and caused only a slight formation of CE in macrophages from both types of mice. On the other hand, d<1.006 g/ml lipoproteins obtained from LDL-R deficient mice fed a high fat diet, beta-VLDL with apoE, were avidly taken up by and markedly stimulated CE formation in wild type macrophages, but not in macrophages lacking the LDL-R. The degradation of 125I-labeled-apoE-containing beta-VLDL by wild type MPM was poorly inhibited by unlabeled human LDL, and beta-VLDL without apoE had no effects. In conclusion, we propose that the in vitro uptake of native apoE-enriched lipoproteins by murine macrophages is primarily mediated by the LDL receptor and not by other apoE-recognizing receptor systems such as: the LDL receptor related protein, the VLDL receptor or the triglyceride-rich lipoprotein receptor.

Animals↗