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Biomedical subjects

Z Q Chen

Publications and source records attributed to Z Q Chen.

At least 37 records · Page 2Linked to original sources

Inhibition of coronary thrombosis and local inflammation by a noncarbohydrate selectin inhibitor.

We tested the hypothesis that selectin inhibition with blocking antibodies or a small-molecular-weight inhibitor of L-, P-, and E-selectin, methoxybenzoylpropionic acid (MBPA), prevents thrombus formation in a canine coronary Folts' model. Cyclic flow variations (CFVs) were induced by crush injury and constriction of the left anterior descending coronary artery in dogs. Systemic infusion of antibodies to P- and L-selectin abolished CFVs, respectively, in 50% and 17% of treated dogs [P = not significant (NS)]. The combination of P- and L-selectin antibodies suppressed CFVs in 60% of treated dogs (P = NS). In contrast, systemic selectin blockade by intravenous infusion or local adventitial application of MBPA markedly reduced CFVs and, in addition, reduced myocardial myeloperoxidase (MPO) activity. We conclude that inhibition of L-, P-, and E-selectin binding by a small-molecular-weight, noncarbohydrate compound markedly reduces arterial thrombosis, whereas systemic administration of antibodies to L- and P-selectin fail to reproduce this antithrombotic effect. These results underscore the role of selectins in the pathogenesis of arterial thrombosis under high shear stress and suggest that inhibition of P- and L- selectin may not suffice to prevent thrombus formation in this model. The role of E-selectin in thrombus formation in this model awaits further testing.

Animals↗

Surface modification of A12O3 bioceramic by NH2+ ion implantation.

Ion implantation technique was applied to graft the -NH2 amidogen radicals onto the surface of Al2O3 bioceramic. Fourier transform infrared spectroscopy (FTIR) was used to confirm the presence of the implanted radicals on the Al2O3 ceramic surface. It was found that the amount of grafted amidogen radicals was proportional to the dosage of NH2+ ions used during the ion implantation. Furthermore, when implantation energy of 100 keV was used, maximum amount of -NH2 radicals would be grafted on the Al2O3 ceramic surface. The biocompatibility of the implanted Al2O3 ceramic was also investigated, and the results indicate that the implanted surface has better biocompatibility with animal bone tissue than the plain ceramic surface.

Aluminum Oxide↗

The emerging clinical potential of cardiovascular gene therapy.

Despite considerable progress, pharmacological therapies have not provided a complete solution for common cardiovascular problems, including recurrent thrombosis, restenosis, and vein graft deterioration. Optimal drug dosage, reproducing plasma concentrations achieved in animal studies establishing proof-of-principle, would often be too toxic to administer, especially when given over prolonged periods of time. Local gene therapy aims at overexpressing proteins that: (1) regulate the cell cycle of VSMC; (2) inhibit VSMC migration; (3) endow the endothelium with its vasoprotective properties; and (4) stimulate growth of endothelium and angiogenesis. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote VSMC proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, and there, it can extend the presence of this agent to weeks and, with some gene vectors, to many months. The clinical potential of this approach has led to the initiation of trials that currently evaluate gene therapy approaches to the attenuation of peripheral and myocardial ischaemia and the prevention of vein graft disease.

Animals↗

Extensive conservation of sex chromosome organization between cat and human revealed by parallel radiation hybrid mapping.

A radiation hybrid (RH)-derived physical map of 25 markers on the feline X chromosome (including 19 Type I coding loci and 6 Type II microsatellite markers) was compared to homologous marker order on the human and mouse X chromosome maps. Complete conservation of synteny and marker order was observed between feline and human X chromosomes, whereas the same markers identified a minimum of seven rearranged syntenic segments between mouse and cat/human X chromosome marker order. Within the blocks, the feline, human, and mouse marker order was strongly conserved. Similarly, Y chromosome locus order was remarkably conserved between cat and human Y chromosomes, with only one marker (SMCY) position rearranged between the species. Tight linkage and a conserved gene order for a segment encoding three genes, DFFRY-DBY-UTY in human, mouse, and cat Y chromosomes, coupled with demonstrated deletion effects of these genes on reproductive impairment in both human and mouse, implicates the region as critical for Y-mediated sperm production.

Animals↗

Xylene-induced effects on brain neurotransmitters, behavior and fos protein in rats.

Male Sprague-Dawley rats administered xylene intraperitoneally on alternate days at a dose of 125 or 250 mg/kg for 30 days exhibited no marked changes in locomotor activity, learning and memory capacity. However in rats given xylene on alternate day at a dose of 500 mg/kg for 30 days, a significant decrease in locomotor activity, deficits in learning ability and memory loss were detected. These xylene-induced behavioral changes were associated with a decrease in beta-endorphin and leuenkaphlin concentrations in the pons-medulla. On the contrary, xylene at a dose of 500 mg/kg increased the beta-endorphin level in caudate and c-fos expression in hippocampus. These data suggest that the xylene-induced behavioral alterations might be associated with the expression of Fos protein in the hippocampus.

Animals↗

[Opioid mu receptors in caudate nucleus contribute to electroacupuncture and Sm I generating inhibition on nociceptive responses of Pf neurons].

The present experiments aimed to investigate whether the caudate nucleus (Cd) was involved in cortical sensorimotor area I (Sm I) generating descending modulation of the parafascicular nucleus (Pf) in acupuncture analgesia (AA), and what type of opiate receptors in Cd were involved. It was found that nociceptive responses of Pf neurons could be inhibited by electroacupuncture (EA) and excitation of Sm I before lesion of Cd, but not after lesion. After microinjection of naloxone beta-FNA, the specific antagonist for opioid mu receptors, into Cd,the inhibitory effect of EA or activation of Sm I on nociceptive responses of the Pf neurons was abolished, but it was not influenced by microinjection of nor-BNI and ICI174,864, the specific antagonists for opioid kappa and delta receptors, respectively. Together with our previous findings that EA could activate cortical neurons to participate in descending modulation of activities of Pf neurons, the present results suggest that Cd is associated with Sm I generating descending inhibition on nociceptive responses of Pf neurons in AA, and it is most likely that opiates in Cd may be involved in this inhibition through mu but not kappa or delta receptors.

Acupuncture Analgesia↗

[The influence of different treatment of the etched enamel on bracket bonding effect]

OBJECTIVE:To inquire into the influence of three different treatment of the etched enamel on bracket bonding effect. METHODS:Compared the bracket bonding failure rate and ARI counts of 30 cases which treat the etched enamel surface with 5s air-water gun rinsing, wet cotton ball wiping and alcohol cotton ball wiping respectively. RESULTS: The bracket bonding failure rate of the group which rinse the etched enamel 5s with air-water gun in the lowest one.There are statistically significant difference between this group and two others.The ARI count of this group is higher than that of others. CONCLUSION:The results suggest that rinse the etched enamel with the air-water gun is a very important step to prevent the bracket bonding failure.

Journal Article↗

Localization of the human CXC chemokine subfamily on the long arm of chromosome 4 using radiation hybrids.

All 12 of the human CXC chemokine genes were physically mapped using gene-specific PCR primers and the GenBridge 4 radiation hybrid panel. Nine genes, PF4, PF4V1, GRO1, GCP2, PPBP, IL8, GRO2, GRO3, and SCYB5, were assigned within a 1.8-cR interval of one another on 4q. Two additional genes, MIG and INP10, map within 0.5 cR of each another and 6 cR distal to the above-mentioned group. The final gene, SDF1, is localized on 10q. Phylogenetic analyses of amino acid sequences revealed that SDF1 is the most divergent member and that the physically separated MIG-INP10 pair constitutes a distinct evolutionary lineage.

Chemokines, CXC↗

A human vascular endothelial cell model to study angiogenesis and tumorigenesis.

Endothelial cell biology has recently been the subject of considerable interest in thrombosis and cancer research. However, the successful establishment of immortalized human endothelial cells which retain differentiated cell characteristics has been rare. We have successfully established immortalized human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16 E6-E7. HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells. Both E6 and E7 cultures had an extended lifespan but eventually underwent senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in culture but did not undergo malignant conversion. Telomerase activity was not detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4-5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial origin. The line expressed integrin subunits (alpha(v)beta3, alph(v)beta5, beta1, alpha2, alpha3, beta4 and alpha6) consistent with an endothelial origin. The higher passage of 4-5-2G line showed a similar intensity of integrin immunostaining to that of primary HUVECS. Subsequent infection of these immortal cells with the Kirsten murine sarcoma virus which contains an activated K-ras oncogene induced morphological transformation that led to the acquisition of invasion capability and neoplastic properties. Telomerase was also detected in the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful for studies of the molecular mechanisms underlying normal and neoplastic endothelial cell proliferation and migration, and might also provide an in vitro model for development of pharmacologic and gene therapy for cardiovascular thrombosis and cancer.

Cell Line, Transformed↗

Increased expression of the rat myometrial oxytocin receptor messenger ribonucleic acid during labor requires both mechanical and hormonal signals.

We investigated the expression of the mRNA encoding the oxytocin receptor (OTR) in rat myometrium throughout gestation and its regulation by progesterone and mechanical stretch. Using a semiquantitative reverse transcription-polymerase chain reaction approach, OTR mRNA was found to increase abruptly at the onset of spontaneous labor at term. Progesterone (4 mg/day) starting on Day 20 of gestation blocked this increase. Ovariectomy on Day 17 induced preterm labor 96 h after surgery and a significant increase in myometrial OTR mRNA levels 48 and 96 h after surgery. Both preterm labor and the rise in myometrial OTR expression were blocked by progesterone. To investigate the effects of stretch on myometrial OTR mRNA expression, unilaterally pregnant rats underwent either sham operation or placement of a tube in the nongravid uterine horn to distend the myometrium. On Day 20, stretch had no effect on OTR expression in the nongravid horns. During labor, OTR mRNA was highly expressed in the gravid horns as well as the nongravid stretched horns. In contrast, the level remained low in the nongravid unstretched horns. These results indicate that expression of rat myometrial OTR mRNA during pregnancy and labor is regulated by coordinated interactions between mechanical and endocrine signals.

Animals↗

Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil.

Previously, we demonstrated that protein-DNA interactions at the drug response element (DRE) in the human apoA-I promoter were important for the induction of apoA-I gene expression by gemfibrozil. We now report the cloning and characterization of a DRE transactivating factor. The cloned protein is identical to the putative helicase and potential transcription factor human S mu binding protein-2 (HSmuBP2). It is also related to glial factor-1 (GF1), an incomplete version of HSmuBP2 lacking the first 494 and the last 128 amino acids. Gel mobility shift assays demonstrated that HSmuBP2 binds apoA-I DRE oligomers and forms a specific protein-DNA complex. Northern blot analysis showed that HSmuBP2 mRNA is expressed at various levels in a wide range of human tissues. Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSmuBP2 or GF1 induced apoA-I proximal promoter activity by 3-fold and that the apoA-I DRE was necessary for transactivation. Additionally, we demonstrated that transactivation was increased a further 2- to 3-fold by exposing the cells to gemfibrozil. Together these observations indicate that HSmuBP2 acts as a transcription factor that regulates apoA-I gene expression in hepatoma cells and whose activity may be stimulated by gemfibrozil treatment.

Apolipoprotein A-I↗

The development of neurobehavioral toxicology in China: the 1994 Hänninen Lecture.

With the rapid growth of industrialization in China, occupational and environmental exposure to chemicals has increased in frequency and in types of chemical exposures. A growing number of Chinese researchers are showing a special interest in exploring the effects of chemicals on the central nervous system. This paper presents a comprehensive review of neurobehavioral toxicology in China. It describes research into the "reference values" of the Neurobehavioral Core Test Battery (NCTB) tests, the development and improvement of the computer-administered Chinese version of the Neurobehavioral Evaluation System (NES-C), and exploration of related biomarkers. On the basis of this research, baseline data for the reference values for six subtests of the NCTB were preliminarily recommended. The upgraded NES-C2 has proven to possess higher stability and validity compared with the previous version, NES-C. Biomarkers derived from the changes in levels of neurotransmitter metabolites might be used as supplementary biomarkers of Pb-induced neurotoxicity.

Adolescent↗

Human hematopoietic cell express two forms of the cytokine receptor common gamma-chain (gamma c).

Recent studies have revealed that the gamma-chain of the IL-2 receptor is shared by the receptors for IL-4, IL-7, IL-9, IL-13, and IL-15, and it is therefore also referred to as the common gamma-chain (gamma c). Mutations of gamma c result in X-linked severe combined immunodeficiency syndrome in humans, indicating that gamma c is essential for normal development and function of the immune system. We demonstrate that human hematopoietic cells express two gamma c transcripts differing in their carboxyl terminal coding region. One transcript is the previously reported sequence (gamma c-long), whereas the newly identified sequence exhibits a deletion of 72 nucleotides close to the 3'-end of the open reading frame (gamma c-short). This alteration predicts a loss of 24 amino acids including a conserved tyrosine residue which is shared by several members of the cytokine receptor family. The presence of these two distinct forms of gamma c transcripts was demonstrated by sequencing of reversely transcribed and polymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines and human peripheral blood lymphocytes. Furthermore, the two variants were present in peripheral blood lymphocytes from both female and male donors, which rules out allelic variants since gamma c is a single copy gene located on the X chromosome. A truncation mutant at a site near the observed changes in gamma c-short has been reported by others to alter biochemical events activated by cytokines. This combined with the loss of a potential SH2 "docking" site in gamma c-short suggests that gamma c-long and gamma c-short may link to different signaling pathways and may play an important role in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.

Alternative Splicing↗

Nutritional evaluation of women in urban areas in continental China.

In 1993-1995, a nutritional survey was conducted in China, in which 50 women each in three cities of Beijing, Shanghai and Nanning (thus 150 in total) volunteered to offer 24-hr total food duplicates and peripheral blood samples. People daily took 1,776 kcal (7,431 kJ) energy, 57 g protein, 75 g lipid, 218 g carbohydrate, 439 mg calcium, 24 mg iron, 3,398 mg sodium and 1,521 mg potassium. When compared with the recommended dietary allowance for Chinese, intakes of energy, iron and possibly vitamin C were sufficient in a majority of the participants, but not so in cases of calcium, and several vitamins. The lipid energy ratio was 38% on an average and was higher than 30% in a majority (73%) of the people. BMI, but not the lipid energy ratio, correlated with the serum triglyceride level. In accordance with high iron intake, the prevalence of anemia was low. Inter-city differences were evident in nutrient sources. Thus, Beijing people took more amounts of protein and lipid from meats (including eggs and milk), whereas plant-based foods were important sources of lipid in Shanghai and that of protein in Nanning. Furthermore, consumption of rice was significantly lower in Beijing than in Shanghai and Nanning, whereas wheat consumption was higher in Beijing than in Shanghai and Nanning.

Adult↗

Protein-DNA interactions at a drug-responsive element of the human apolipoprotein A-I gene.

Previously, we demonstrated that when two human hepatoma cell lines, Hep3B and HepG2, were exposed to gemfibrozil, a hypolipidemic drug, a 2-fold induction in apolipoprotein A-I (apoA-I) mRNA levels resulted. To determine if mRNA stabilization was responsible for the changes in apoA-I mRNA levels, the half-lives for apoA-I mRNA were measured in the presence of actinomycin D with and without gemfibrozil. These experiments revealed no differences in stability. However, nuclear run-off assays indicated that the transcription rate of the apoA-I gene was increased 2-fold in gemfibrozil-treated cells. Transient transfection experiments also indicated that the induction of apoA-I mRNA level in response to gemfibrozil is mediated at the transcriptional level. We have identified two copies of the "drug-responsive element" (DRE) in the apoA-I promoter region that may be responsible for the increase in apoA-I transcriptional activity by gemfibrozil. Using gel mobility shift assays with a synthetic DRE oligonucleotide, we have demonstrated that exposure of Hep3B and HepG2 cells to gemfibrozil resulted in strong induction of a protein-DNA complex. The formation of this complex is highly sequence-specific as indicated by the DNA competition experiments. The drug-inducible nuclear proteins bind to the DRE of the human apoA-I gene with an apparent Kd of 4.1 nM. Methylation interference experiments have localized the contact sites of nuclear factors to the DRE region. Southwestern blot analyses have identified two groups of drug-inducible nuclear proteins with molecular masses of approximately 30 and 15 kDa. When a copy of synthetic DRE oligonucleotide was inserted upstream of the thymidine kinase promoter and luciferase reporter construct, a significant 2-fold induction in luciferase activity was observed in the presence of gemfibrozil following transient transfection of two human hepatoma cell lines, HepG2 and Hep3B. However, a plasmid containing one copy of mutated apoA-I-DRE oligomer did not confer responsiveness to gemfibrozil treatment. Furthermore, pGL2 (apoA-I -250 mutant DRE), which carried an internal mutation of the DRE in the human apoA-I proximal promoter region, showed no increase in luciferase activity in response to gemfibrozil. These results implicate protein-DNA interactions at the DRE region in the transcriptional induction of human apoA-I gene expression by gemfibrozil.

Apolipoprotein A-I↗

Changes in cervical canal spinal volume during in vitro flexion-extension.

STUDY DESIGN: Quasistatic flexion and extension loads were applied in vitro to lower cervical spines. The flexion-extension motion produced was checked for physiologic relevance. OBJECTIVES: To examine the changes in the volume of the cervical spinal canal in flexion-extension motion. SUMMARY OF BACKGROUND DATA: Many papers have been published concerning the cervical canal volume as inferred from standard lateral radiographs. This study compares the inferred (radiographic) volumes and their changes to the physical changes within the spinal canal. METHODS: The lower cervical spines (C2-C7) from 10 cadavers were subject to stepwise flexion and extension in a purpose-built rig. Before this testing, the spinal cord was removed from the canal space of each specimen and replaced by a thin latex tube stoppered and secured at the opening of the canal (at C2) so that the volume of liquid displaced from the tube could be measured. This was done at each loading stage by means of a graduated glass column, and a radiograph of the spine was also taken to allow angular and displacement readings to be taken from C2 to C7. RESULTS: The average recorded change in volume of the spinal canal with flexion-extension motion was 1.9 ml, and showed a significant linear correlation with the dynamic canal width (r = 0.868, P < 0.05) and also with the total angle of flexion or extension (r = 0.979, P < 0.005). The volume of liquid displaced from the canal in lateral bending was much lower than that in flexion-extension motion, and only amounted to about 0.2 ml. The angular ranges of motion produced at each level were compared to previous results obtained in vivo, and no significant differences between the angular displacements found in vivo and in vitro under this experimental arrangement were seen. CONCLUSIONS: The loading regime described in this study causes angular displacements similar to those in vivo, and on this basis is a physiologically relevant loading pattern. The change in the volume of the spinal canal between C2 and C7 shows linear relationships with the angle of flexion and the dynamic canal width.

Adult↗

Identification of two regulatory elements within the promoter region of the mouse connexin 43 gene.

To define the minimal sequences required for expression of the connexin 43 gene (cx43) in myometrial cells, we generated 5' deletion constructs of a fragment extending 1686 base pairs upstream and 162 base pairs downstream of the transcription start site and determined their ability to drive expression of the chloramphenicol acetyltransferase reporter gene in transfected myometrial cell lines. Our investigation revealed two cis-acting regulatory elements within this fragment. Deletion of a region extending from -102 to -92 led to an increase of the promoter activity by greater than 10-fold, indicating a presence of a repressor element. Deletion of a region extending from -72 to -62 caused a decrease of the promoter activity of a similar extent, implying the existence of a positive element. Electrophoretic mobility shift assays demonstrated that synthetic oligonucleotides derived from these two small regions can each bind with a nuclear protein(s) prepared from myometrial cells, and an introduction of three and two base substitutions into each of these oligomers was sufficient to abolish their protein binding capability. These same mutations, when incorporated in the chloramphenicol acetyltransferase constructs, diminished regulatory functions of the negative and positive elements, and the protein(s) that bind to these functional elements was found in several tissues known to express cx43 gene.

Animals↗