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Biomedical subjects

J Z Chen

Publications and source records attributed to J Z Chen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intraindividual sequence diversity and a hierarchical approach to the study of mitochondrial DNA mutations.

Investigations of intraindividual sequence diversity in mtDNA are a key step in exploring the linkage between somatic mutations in mtDNA and mitochondrial genome evolution. This paper reports a directional cloning procedure enabling the isolation of multiple copies of the D-loop region of the mitochondrial genome from the fish Ameiurus nebulosus. Sequence analysis of 708 D-loop molecules revealed eight mutants, an average intraindividual mutation frequency of 1.12%. Three different types of mutations were detected but each derived from a single mutational event. By contrasting the spectrum of nucleotide variation at multiple biological levels, one can investigate the effects of spontaneous mutations on genome evolution. Such hierarchical analysis suggested shifts in the type and distribution of mtDNA (mitochondrial DNA) mutations at different biological levels, indicating the need to recognize three different rates of mtDNA sequence change from the cellular to population level.

Animals↗
PubMed1999

Terminal branch haplotype analysis: a novel approach to investigate newly arisen variants of mitochondrial DNA in natural populations.

The discrimination of recent mutational derivatives from ancestral variation is a critical antecedent to any effort which aims to identify the factors modulating the rates of origin and persistence of new mutants. We propose that newly arisen mtDNA variants, which we designate as terminal branch haplotypes (TBHs), can be recognized by joint sequencing and phylogenetic analysis. This study examined mtDNA diversity in natural populations of the brown bullhead (Ameiurus nebulosus) from four heavily contaminated sites and three relatively pristine locations. While sequence analysis of the mtDNA D-loop region revealed that TBHs were prevalent in these populations, contaminant exposure appeared to play a minor role in their generation. Instead, most TBHs likely arose due to spontaneous mutations with variation in their incidence among sites reflecting the impact of demographic factors.

Animals↗
PubMed1999

Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated.

Sphingolipid and cholesterol-rich Triton X-100-insoluble membrane fragments (detergent-resistant membranes, DRMs) containing lipids in a state similar to the liquid-ordered phase can be isolated from mammalian cells, and probably exist as discrete domains or rafts in intact membranes. We postulated that proteins with a high affinity for such an ordered lipid environment might be targeted to rafts. Saturated acyl chains should prefer an extended conformation that would fit well in rafts. In contrast, prenyl groups, which are as hydrophobic as acyl chains but have a branched and bulky structure, should be excluded from rafts. Here, we showed that at least half of the proteins in Madin-Darby canine kidney cell DRMs (other than cytoskeletal contaminants) could be labeled with [3H]palmitate. Association of influenza hemagglutinin with DRMs required all three of its palmitoylated Cys residues. Prenylated proteins, detected by [3H]mevalonate labeling or by blotting for Rap1, Rab5, Gbeta, or Ras, were excluded from DRMs. Rab5 and H-Ras each contain more than one lipid group, showing that hydrophobicity alone does not target multiply lipid-modified proteins to DRMs. Partitioning of covalently linked saturated acyl chains into liquid-ordered phase domains is likely to be an important mechanism for targeting proteins to DRMs.

Acylation↗
PubMed1999

Directed termination of the polymerase chain reaction: kinetics and applications in mutation detection.

We describe a PCR-based method (DT-PCR) that integrates both DNA amplification and directed chain termination into a single-step process. This method exploits unbalanced nucleotide concentrations to induce the polymerase chain reaction to terminate at specific nucleotide sites, leading to the generation of two sets of nested termination fragments from genomic DNA. The kinetic mechanism underlying the termination process is outlined and the application of this method to the detection and characterization of mutations in fragments as long as 1 kb is described. The method is effective for the analysis of both haploid and diploid genomes, and not only allows the recognition of both indels (insertions and deletions) and nucleotide substitutions, but also enables the determination of their position in a single-step fashion.

Animals↗
PubMed1998

A 3D-QSAR study on ginkgolides and their analogues with comparative molecular field analysis.

Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm was used to study the correlation between the physicochemical properties and the in vitro bioactivities of ginkgolide analogues. The correlation derived from CoMFA analysis has a good predictive capability. Based on the result of CoMFA analysis, we designed some compounds. Pharmacological assay indicated that three of these new designed compounds are 2 and 4 times more potent than that of ginkgolides.

Diterpenes↗
PubMed1998

Analysis of electronic structures of physostigmine analogs.

AIM: To elucidate the action mechanism and structural prerequisites of 21 physostigmine analogs as acetylcholinesterase inhibitors at the molecular level, and help the rational design of these dihydroindoline inhibitors. METHODS: Initial structures of these compounds were built and minimized by SYBYL 6.2 molecular modeling software. Conformations of those molecules with the highest predictive abilities in the Comparative Molecular Field Analysis model were chosen to the semiempirical quantum chemical calculations. RESULTS: (1) The highest occupied molecular orbital (HOMO) consisted mainly of the orbitals in phenyl group and N1 atom; the lowest unoccupied molecular orbital (LUMO) of the molecules was contributed from phenyl group and C11 atom. While the HOMO energies did not show any recognizable relationship with activity, the LUMO energies showed a decreased tendency with increasing activity. The active compounds showed lower LUMO energies. (2) The carbon atom (C11) had the most positive net atom charge. The most active compound had the most positive charge on this carbon, but had the lower charges on the carbonyl oxygen (O12) which was the most negative charge atom. (3) The bond order of carbon-oxygen bond (C11-O10) was invariant across the series of the compounds. (4) Compounds with too high or too low total dipole moment had lower activities, while the most active one had a lower molecular polarizability. CONCLUSION: A molecular model was suggested to explain the possible mode of action by which these compounds inhibit acetylcholinesterase.

Cholinesterase Inhibitors↗
PubMed1997

Binding conformers searching method for ligands according to the structures of their receptors and its application to thrombin inhibitors.

AIM: To develop a method of finding binding conformers for ligands according to the three-dimensional structures of their receptors. METHODS: Combining the systematic search method of ligand with the molecular docking approach of ligand fitting into its receptor, we developed a binding conformer searching method for ligands. RESULTS: The binding conformers of phosphonopeptidyl thrombin inhibitors were recognized. The binding (interaction) energies between these inhibitors and thrombin were calculated with molecular mechanical method. CONCLUSION: Both of the total binding energies and steric binding energies have good correlations with the inhibitory activities of these thrombin inhibitors, demonstrating that our approach is reasonable. It can also be used to explain the inhibition mechanism of thrombin interacting with these inhibitors.

Binding Sites↗
PubMed1996

Spin trapping study in the lungs and liver of F344 rats after exposure to ozone.

Fischer 344 rats were injected with the spin traps C-phenyl N-tert-butyl nitrone (PBN, 150 mg/kg bw, ip) or 4-pyridine-N-oxide N-tert-butyl nitrone (POBN, 775 mg/kg bw, ip), and exposed to clean air or 2 ppm ozone for two hours. The presence of spin adducts was determined by electron paramagnetic resonance (EPR) spectroscopy of chloroform extracts of lung and liver homogenates. No significant levels of adducts were detected in the lungs of air control animals. Benzoyl N-tert-butyl aminoxyl, attributed to direct reaction of ozone with PBN, and tert-butyl hydroaminoxyl, the scission product of the hydroxyl adduct of PBN, were detected in the lungs of ozone exposed rats. EPR signals for carbon-centred alkoxyl and alkyl adducts were also detected with PBN in the lungs and liver of animals exposed to ozone. With POBN, only carbon-centred alkyl radicals were detected. Senescent, 24 months old rats were found to retain about twice more 14C-PBN in blood, heart and lungs by comparison to juvenile, 2 months old animals. Accordingly, the EPR signals were generally stronger in the lungs of the senescent rats by comparison to juvenile rats. Together, the observations were consistent with the previously proposed notion that a significant flux of hydrogen peroxide produced from the reaction of ozone with lipids of the extracellular lining, or from activated macrophages in the lungs could be a source of biologically relevant amounts of hydroxyl radical.

Animals↗
PubMed1994

3D-QSAR study on ether and ester analogs of artemisinin with comparative molecular field analysis.

Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to study the correlations between the physicochemical properties and the in vitro activities of a series of ether and ester analogs of artemisinin. Four alignment models were used in the CoMFA investigation. The correlations derived from CoMFA analysis with the four alignments proved all to have good predictive values. The steric field predictive model of alignment B is accordant with the experimental results of Avery M A, et al: J Med Chem 1993; 36: 4264-75. The electrostatic field predictive results of alignments A, B, and C are consistent with our previous result of quantum chemical calculation. The highest rcross2 of alignment D, indicated that the side chain of -C6-O2-O1-C10-O3-C7-O4-C12-O5- and atom C16 are important groups of artemisinin analogs for antimalarial activity.

Antimalarials↗
PubMed1994

[Intraperitoneal perfusion of compound injection of salvia miltiorrhiza with dachengqi decoction in treating adhesive intestinal obstruction].

47 cases of adhesive intestinal obstruction after decompression operation were treated with intraperitoneal perfusion of compound injection of Salvia Miltiorrhizam intraperitoneally before closing the abdominal cavity and Dachengqi decoction oral given post-operatively. Follow up study for 2-9 years showed the effective rate was 100% except one case died of other unrelevant disease. Another 38 cases of the same disease and same operation procedure were selected as the control group, which were given antibiotics intraperitoneally before closing the abdominal cavity. The effective rate was 73.38%. The result in the therapeutic group was significantly better than that in the control group (P < 0.01).

Adolescent↗
PubMed1994

[Measurement of plasma fibronectin concentrations in normal pregnancy and pregnancy induced hypertension and its clinical significance].

Plasma fibronectin (Fn) concentrations were measured in 472 cases of normal pregnancy and pregnancy induced hypertension (PIH), and 50 cases of normal individuals using radioimmune turbidity method. The results showed that the mean value of Fn in 390 cases of normal pregnancy with various weeks of gestation was 445 +/- 159 mg/L significantly higher than the average of 299 +/- 76 mg/L in 50 cases of normal individuals and 250 +/- 89 mg/L in 22 cases of normal women. As pregnancy progressed, the plasma Fn value increased slightly. The 82 cases of PIH had an average plasma Fn level of 783 +/- 168 mg/L, which was significantly higher than that in normal pregnancy. If plasma Fn concentrition of 600 mg/L was used as cut-off point for the diagnosis of PIH, the sensitivity reached to 83%. Plasma Fn level increased as the disease of PIH progressed. Therefore, plasma Fn concentrition could be used as a reliable indicator to the severity of PIH.

Adult↗
PubMed1990

Heparin inhibits EcoRI endonuclease cleavage of DNA at certain EcoRI sites.

Studies presented here demonstrate that heparin inhibits EcoRI endonuclease cleavage of DNA whereas related proteoglycans show no effect. The inhibition occurs at particular EcoRI sites that are near or overlap with palindromic sequences in the murine lambda 5 and Lyt-2 genes. Endogenous heparin from peritoneal mast cells co-isolates with DNA and inhibits digestion of peritoneal cell DNA at the inhibitable sites. Digestion of spleen DNA is inhibited at the same sites when commercial heparin is added prior to digestion. In both cases, the inhibition is abolished by pre-treating the DNA with heparinase. Thus, potential artifacts in restriction fragment length analyses could occur with DNA isolated either from cells that are naturally rich in heparin or from cells to which heparin has been added, e.g., as an anticoagulant.

Animals↗
PubMed1990

Differences in glycoprotein complexes associated with IgM and IgD on normal murine B cells potentially enable transduction of different signals.

Studies presented here demonstrate that IgM and IgD molecules on normal murine B lymphocytes exist in different, noncovalently associated molecular complexes containing distinct but potentially related glycoproteins. The glycoproteins in these complexes, particularly those associated with IgD, show striking differences in various lymphoid organs and in X-linked immunodeficient (Xid) mice. These differences are due in part to post-translational processing. They apparently reflect the differential expression of the Ig-associated glycoproteins in the various B cell subpopulations and lineages and the differential distribution of the subpopulations and lineages in the various lymphoid organs. In addition, they reflect structural differences in the IgM and IgD complexes which, we suggest, permit differential signal transduction by IgM and IgD on the same B cell.

Animals↗
PubMed1990

Orthotopic homotransplantation of vascularized composite mandibular tissue in rabbits immunosuppressed with cyclosporine A.

To develop the surgical model, composite mandibular tissue was transplanted at the same site. Revascularization was accomplished by end-to-end anastomosis of the facial vessels using standard microvascular techniques. A total of 33 vascularized composite mandibular tissue allografts were similarly performed between two incompatible strains of rabbit. In a control group of 9 animals, no immunosuppression was administered. All of these allografts were rejected acutely within 10 days after surgery. 7 allograft recipients were immunosuppressed with azathioprine and prednisone at 5 mg/kg.d and 2 mg/kg.d, respectively. Their allografts were also rejected acutely within 10 days. 17 allograft recipients were immunosuppressed with cyclosporine A (CsA). All allografts showed primary wound healing and hair growth and took on normal appearance. 8 of these recipients were given CsA at 5 mg/kg.d i.v. and their allografts were rejected at a mean time of 17.9 days. The remaining 9 recipients given CsA at 10 mg/kg.d i.v. rejected their allografts at a mean time of 36.1 days. In 3 of them, the rejection was reversed with CsA (20 mg/kg.d) injection for five days successfully, and one allograft survived more than 100 days. This pilot study suggests that the surgical model is reliable and that CsA will be useful as an immunosuppressive agent in the study of vascularized composite mandibular tissue allografts.

Animals↗
PubMed1990

[Clinical effect of chemotherapy combined with Chinese herbs and western drugs on leukocytes of gastric cancer patients].

This study observed the effect of chemotherapy combined with Chinese herbs and western drugs on white blood cell count in 31 patients with gastric cancer. These patients were divided into 3 groups: (1) Fu Zheng (strengthen the body resistance) with invigorating the Spleen and Kidney recipe; (2) Fu Zheng with western drugs raising WBC and enhancing immunity; (3) Gong Xiao (eliminating the evil factors and mass) with promoting blood circulation to remove blood stasis recipe or eliminating the evil factors and mass recipe. After chemotherapy, the mean of WBC count was greater than 4.0 X 10(9)/L in group I; less than 3.5 X 10(9)/L in group II; less than 3.0 X 10(9)/L in group III. Because of WBC count below 3.0 X 10(9)/L, in group II there were 5 cases (5/14) whose chemotherapies had to be discontinued, and in group III there were 4 cases (4/6). While all patients were completed their chemotherapies in group I. Its statistical difference was significant (P less than 0.05). It suggested that invigorating the Spleen and Kidney recipe had specific effect on decreasing the toxicity and side effect of chemotherapy, preventing bone marrow suppression and leukopenia, and was better than western drugs used in group II. It showed in the treatment of cancer with TCM, we must pay attention to the relationship between the Fu Zheng and the Gong Xiao.

Adult↗