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Biomedical subjects

Q Zhao

Publications and source records attributed to Q Zhao.

At least 109 records · Page 6Linked to original sources

[Off pump coronary artery bypass grafting in 51 cases].

OBJECTIVE: To study the cost-effective minimal invasive coronary bypass surgery which decreases the complication associated with cardiopulmonary bypass, alleviates postoperative pain, and promotes recovery. METHODS: From August 1998 to November 1999, fifty-one patients underwent minimal invasive coronary bypass surgery with off pump technique. Age range was from 39 to 80 years (average 64). Thirty-five patients suffered from myocardial infarction and nine patients diabetes. Left ventricular ejection fraction was from 20%-72% (average 53%). All procedures were completed through medial sternotomy. Stabilizers of CTS, Octopus, and USSC were applied. The average graft was 2.7 per case. RESULTS: The operative mortality was 1.9%. The average ICU and hospital stay were 1.2 and 6 days, respectively. The average chest drainage and blood transfusion were 415 ml and 160 ml, respectively. Fifty patients survived from surgery. All survived patients had no symptoms of angina during the short-term follow-up (1 to 8 months). Two patients were followed up by postoperative coronary angiography, which showed a satisfactory anastomosis rate of 100%. CONCLUSIONS: Minimal invasive coronary bypass surgery is safe, cost-effective, and suitable for patients with high risk of extracorporeal circulation. It can also be used for multivessel disease.

Adult↗

[Influence of a G/A substitution at -75 bp promoter region of apolipoprotein A I gene and wine consumption on the plasma apolipoprotein A I levels in Yi and Han Chinese].

OBJECTIVE: To study the influence of a common polymorphism of the human apolipoprotein A I gene promoter at a position of -75 bp upstream of the transcription start site and wine consumption on plasma lipid levels. METHODS: 742 healthy Yi and Han healthy subjects all above 15 years old to be the total population which was divided into three samples, namely, Yi-farmer sample, Yi-emigrant sample and Han-resident sample for this study. Estimations of plasma lipids and apolipoproteins were carried on through an auto-analyzer. Genetic DNA was prepared from the frozen blood clot using Triton x-100 lysis technique. Amplification of a 432 bp fragment of the apoA I gene promoter was performed via the PCR, followed by restriction digestion, electrophoresis and identification of the genotypes involved. Data analysis was done at last. RESULTS: Four groups of alcohol consumption were defined: the non-drinkers, 1 - 25 g alcohol intake/day, 26 - 75 g alcohol/day and > 75 g alcohol/day. A tendency of a mild persistent elevation of plasma HDL-C and apoA I was noticed corresponding to an increase of the amount of alcohol intake, and with no evidence of threshold effect observed in the samples of both the Yi-farmers and the Han people. Similar phenomenon was obtained in the sample of Yi-emigrants, but no statistical significance. The frequencies of the A allele of all 3 samples were similar. In Han and Yi-emigrant samples, the drinkers with genotypes of GG had a higher plasma HDL-C and apoA I level than that of the non-drinkers with the same genotypes. Drinkers with A allele had a lower plasma HDL-C and apoA I level than that of drinkers without A allele, and the non-drinkers with A allele had a higher levels of apoA I than of non-drinkers with genotypes of GG. It is estimated that 18% of the variability of plasma apoA I level could be explained by the G/A polymorphism in non-drinkers of Yi-emigrants (F = 8.94, P < 0.01). CONCLUSIONS: Current data suggest that a moderate alcohol consumption or a G to A substitution could make a lower incidence of CHD, but the beneficial effect of one will be negated by the other when both factors occur simultaneously. This finding is seemed valuable for a further study on the effect of the environmental factor or genetic factor in effecting the plasma apoA I level afterwards.

Adolescent↗

[Pharmacognostical identification of one Rhizoma Drynariae habitually used species from Yunnan].

The species recorded on the "Rhizoma Drynariae" item of Chinese Pharmacopeia is the dry rhizoma of Drynaria fortunei from Polypodiacae. But in Yunnan province, many plants (including D. delavayi) are habitually used as Rhizoma Drynariae. In this article the authors identified D. delavayi on Chinese medinal materials discriptions, microscopic characters and TLC. This proved evidences for the utilization and identification of D. delavayi in some extent.

Chromatography, Thin Layer↗

The effects of triptolide on HLA antigens expression of corneal epithelial cells induced by interferon-gamma in vitro.

OBJECTIVE: To observe the effects of immunosuppressants triptolide (TL) and cyclosporine A (CSA) on HLA antigens expression induced by interferon-gamma(INF-gamma) in vitro. METHOD: By using an indirect immunofluorescent method and analysing with ACAS-570, the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-gamma. After incubation with one of the immunosuppressants (CSA, TL) for 72 hrs, the amount of HLA-A BC and HLA-DR antigens was measured. RESULT: There was no significant difference (P > 0.05) between the group with CSA and the positive control group without CSA. In contrast to CSA, TL dramatically inhibited INF-gamma induced expression of HLA antigens of corneal epithelial cells (P < 0.001), compared with the control group without TL. CONCLUSION: TL had direct inhibition on the expression of HLA-ABC and HLA-DR antigens induced by INF-gamma in vitro, while CSA had no obvious inhibition.

Cells, Cultured↗

Site of chemical modifications in CpG containing phosphorothioate oligodeoxynucleotide modulates its immunostimulatory activity.

Phosphorothioate oligodeoxynucleotides containing CpG motifs have immunostimulatory activity. Appropriate substitution of deoxynucleosides in the flanking region of CpG-containing phosphorothioate oligodeoxynucleotides with 2'-O-methylribonucleosides results in significant decreases or increases in their immunostimulatory activities. The results provide insights in how to chemically modify phosphorothioate oligodeoxynucleotides containing CpG motifs to suppress or enhance their immunostimulatory activity for different therapeutic uses.

Adjuvants, Immunologic↗

The efficient removal of endotoxins from insulin using quaternized polyethyleneimine-coated porous zirconia.

The synthesis and use of a zirconia-based, alkali-stable strong anion-exchange stationary phase are described for the removal of pyrogenic lipopolysaccharides (LPS) from insulin. The strong anion-exchange material is produced by deposition of polyethyleneimine (PEI) onto porous zirconia particles, followed by cross-linking with a novel reagent, 1,2-bis-(2-iodoethoxy) ethane, and quaternization with iodomethane. Physical characterization of the chromatographic support shows that it has an ion-exchange capacity of 0.6 mmol/g, and 82% of the amine sites on the surface are in quaternized form. Isocratic elution of small benzoic acid derivatives shows good column efficiency. The two primary virtues of this material are its chemical stability under alkali conditions (up to pH 13) and its lower hydrophobicity compared to previously described alkali-stable PEI-coated zirconia supports cross-linked with 1,10-diiododecane. Using this new zirconia-based phase, a purification protocol is developed for the efficient removal of Escherichia coli 0111:B4 LPS from bovine insulin samples. An endotoxin clearance rate of up to 1.3 x 10(8) was attained. Endotoxin levels were reduced to less than 5 endotoxin units/ml even at initial contamination levels as high as 5.0 x 10(6) endotoxin units/ml. Furthermore, endotoxin adsorbed to the porous zirconia column may be easily removed (depyrogenated) using alkali for repeated purification cycles.

Animals↗

In vitro modulation of macrophage phenotype and inhibition of polymer degradation by dexamethasone in a human macrophage/Fe/stress system.

A new in vitro accelerated biological model, the macrophage-FeCl2-stress system was used for the evaluation of dexamethasone (DEX)-polymer formulations. This model combines the effects of cells (macrophages), transition metal ions (Fe2+), and polymer stress to promote material biodegradation. The cell and material effects of DEX, either in solution or incorporated into a polyetherurethane matrix (DEX/PEU), were monitored. Cell morphology and hydroperoxide formation in the polymer during cell culturing were characterized. After a subsequent treatment with FeCl2 the development of environmental stress cracking in the polymer was evaluated. We attempted to duplicate the biodegradation of PEU in terms of environmental stress cracking (ESC). Our results support the direct involvement of macrophages in polyetherurethane oxidation, probably by inducing hydroperoxide formation in the polymer structure. Under the influence of stress or strain, polymers with sufficient hydroperoxides degrade in the presence of Fe2+ metal ions in a manner that closely resembles the stress cracking that is observed in vivo. By contrast, polymers treated with either agents that inhibit cell activation and/or the oxidative burst, or with cells with no oxidative burst did not show signs of the biodegradative process. We demonstrated a reduction in hydroperoxide formation and no later ESC development in macrophage-cultured PEU in the presence of DEX in solution or in DEX-loaded PEU. We believe the prevention of initial polymer oxidation by reducing the cell's potential to produce oxidative stress at the tissue-biomaterial interface can directly inhibit the ESC degradation of chronically implanted polymers. The in vitro macrophage-Fe-stress system is a valuable tool for reliable assessment and cost-effective evaluation of biomaterials.

Adult↗

Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats.

The effects of histamine on the spatial memory deficits induced by MK-801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2-thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H(1)-receptors.

Analysis of Variance↗

Crystal structure of human quinone reductase type 2, a metalloflavoprotein.

In mammals, two separate but homologous cytosolic quinone reductases have been identified: NAD(P)H:quinone oxidoreductase type 1 (QR1) (EC 1.6.99.2) and quinone reductase type 2 (QR2). Although QR1 and QR2 are nearly 50% identical in protein sequence, they display markedly different catalytic properties and substrate specificities. We report here two crystal structures of QR2: in its native form and bound to menadione (vitamin K(3)), a physiological substrate. Phases were obtained by molecular replacement, using our previously determined rat QR1 structure as the search model. QR2 shares the overall fold of the major catalytic domain of QR1, but lacks the smaller C-terminal domain. The FAD binding sites of QR1 and QR2 are very similar, but their hydride donor binding sites are considerably different. Unexpectedly, we found that QR2 contains a specific metal binding site, which is not present in QR1. Two histidine nitrogens, one cysteine thiol, and a main chain carbonyl group are involved in metal coordination. The metal binding site is solvent-accessible, and is separated from the FAD cofactor by a distance of about 13 A.

Animals↗

Alteration of iron homeostasis following chronic exposure to manganese in rats.

Recent studies suggest that manganese-induced neurodegenerative toxicity may be partly due to its action on aconitase, which participates in cellular iron regulation and mitochondrial energy production. This study was performed to investigate whether chronic manganese exposure in rats influenced the homeostasis of iron in blood and cerebrospinal fluid (CSF). Groups of 8-10 rats received intraperitoneal injections of MnCl2 at the dose of 6 mg Mn/kg/day or equal volume of saline for 30 days. Concentrations of manganese and iron in plasma and CSF were determined by atomic absorption spectrophotometry. Rats exposed to manganese showed a greatly elevated manganese concentration in both plasma and CSF. The magnitude of increase in CSF manganese (11-fold) was equivalent to that of plasma (10-fold). Chronic manganese exposure resulted in a 32% decrease in plasma iron (p<0.01) and no changes in plasma total iron binding capacity (TIBC). However, it increased CSF iron by 3-fold as compared to the controls (p<0.01). Northern blot analyses of whole brain homogenates revealed a 34% increase in the expression of glutamine synthetase (p<0.05) with unchanged metallothionein-I in manganese-intoxicated rats. When the cultured choroidal epithelial cells derived from rat choroid plexus were incubated with MnCl2 (100 microM) for four days, the expression of transferrin receptor mRNA appeared to exceed by 50% that of control (p<0.002). The results indicate that chronic manganese exposure alters iron homeostasis possibly by expediting unidirectional influx of iron from the systemic circulation to cerebral compartment. The action appears likely to be mediated by manganese-facilitated iron transport at brain barrier systems.

Animals↗

Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta.

Recent evidence indicates that nuclear factor-kappaB (NF-kappaB), a transcription factor critically important for immune and inflammatory responses, is activated by a protein kinase cascade. The essential features of this cascade are that a mitogen-activated protein kinase kinase kinase (MAP3K) activates an IkappaB kinase (IKK) that site-specifically phosphorylates IkappaB. The IkappaB protein, which ordinarily sequesters NF-kappaB in the cytoplasm, is subsequently degraded by the ubiquitin-proteasome pathway, thereby allowing the nuclear translocation of NF-kappaB. Thus far, only two MAP3Ks, NIK and MEKK1, have been identified that can activate this pathway. We now show that MEKK2 and MEKK3 can in vivo activate IKK-alpha and IKK-beta, induce site-specific IkappaBalpha phosphorylation, and, relatively modestly, activate an NF-kappaB reporter gene. In addition, dominant negative versions of either IKK-alpha or IKK-beta abolish NF-kappaB activation induced by MEKK2 or MEKK3, thereby providing evidence that these IKKs mediate the NF-kappaB-inducing activities of these MEKKs. In contrast, other MAP3Ks, including MEKK4, ASK1, and MLK3, fail to show evidence of activation of the NF-kappaB pathway. We conclude that a distinct subset of MAP3Ks can activate NF-kappaB.

Calcium-Calmodulin-Dependent Protein Kinases↗

Inhibition by lead of production and secretion of transthyretin in the choroid plexus: its relation to thyroxine transport at blood-CSF barrier.

Long-term, low-dose Pb exposure in rats is associated with a significant decrease in transthyretin (TTR) concentrations in the CSF. Since CSF TTR, a primary carrier of thyroxine in brain, is produced and secreted by the choroid plexus, in vitro studies were conducted to test whether Pb exposure interferes with TTR production and/or secretion by the choroid plexus, leading to an impaired thyroxine transport at the blood-CSF barrier. Newly synthesized TTR molecules in the cultured choroidal epithelial cells were pulse-labeled with [35S]methionine. [35S]TTR in the cell lysates and culture media was immunoprecipitated and separated by SDS-PAGE, and quantitated by autoradiography and liquid scintillation counting. Pb treatment did not significantly alter the protein concentrations in the culture, but inhibited the synthesis of total [35S]TTR (cells + media), particularly during the later chase phase. Two-way ANOVA of the chase phase revealed that Pb exposure (30 microM) significantly suppressed the rate of secretion of [35S]TTR compared to the controls (p < 0.05). Accordingly, Pb treatment caused a retention of [35S]TTR by the cells. In a two-chamber transport system with a monolayer of epithelial barrier, Pb exposure (30 microM) reduced the initial release rate constant (kr) of [125I]T4 from the cell monolayer to the culture media and impeded the transepithelial transport of [125I]T4 from the basal to apical side of epithelial cells by 27%. Taken together, these in vitro data suggest that sequestration of Pb in the choroid plexus hinders the production and secretion of TTR by this tissue. Consequently, this may alter the transport of thyroxine across this blood-CSF barrier.

Animals↗

A physical map of the mouse shaker-2 region contains many of the genes commonly deleted in Smith-Magenis syndrome (del17p11.2p11.2).

We report the construction of a physical map of the region of mouse chromosome 11 that encompasses shaker-2 (sh2), a model for the human nonsyndromic deafness DFNB3. DFNB3 maps within the common deletion region of Smith-Magenis syndrome (SMS), del(17)(p11.2p11.2). Eleven of the genes mapping within the SMS common deletion region have murine homologs on the sh2 physical map. The gene order in this region is not perfectly conserved between mouse and human, a finding to be considered as we engineer a mouse model of Smith-Magenis syndrome.

Abnormalities, Multiple↗

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↗

Pseudo-cyclic oligonucleotides: in vitro and in vivo properties.

We have designed and studied antisense oligodeoxynucleotides (oligonucleotides; oligos) which we call 'pseudo-cyclic oligonucleotides' (PCOs). PCOs contain two oligonucleotide segments attached through their 3'-3'- or 5'-5'-ends. One of the segments of the PCO is an antisense oligo complementary to a target mRNA, and the other is a short protective oligo that is 5-8 nucleotides long and complementary to the 3'- or 5'-end of the antisense oligo. As a result of complementarity between the antisense and protective oligo segments, PCOs form intramolecular pseudo-cyclic structures in the absence of the target RNA. The antisense oligo segment of PCOs used for the studies described here is complementary to an 18-nucleotide-long site on the mRNA of the protein kinase A regulatory subunit RIalpha (PKA-RIalpha). Thermal melting studies of PCOs in the absence and presence of the complementary RNA suggest that the pseudo-cyclic structures formed in the absence of the target RNA dissociate, bind to the target RNA, and form heteroduplexes. The results of RNase H cleavage assays suggest that PCOs bind to complementary RNA and activate RNase H in a manner similar to that of an 18-mer conventional antisense PS-oligo. In snake venom (a 3'-exonuclease) or spleen (a 5'-exonuclease) phosphodiesterase digestion studies, PCOs are more stable than conventional antisense oligos because of the presence of 3'-3'- or 5'-5'-linkages and the formation of intramolecular pseudo-cyclic structures. PCOs with a phosphorothioate antisense oligo segment inhibited cell growth of MDA-MB-468 and GEO cancer cell lines similar to that of the conventional antisense PS-oligo, suggesting efficient cellular uptake and target binding. The nuclease stability studies in mice suggest that PCOs have higher in vivo stability than antisense PS-oligos. The studies in mice showed similar pharmacokinetic and tissue distribution profiles for PCOs to those of antisense PS-oligos in general, but rapid elimination from selected tissues.

Animals↗

Conjugate chemistry and cellular processing of EGF-dextran.

Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

Astatine↗

Circulating intercellular adhesion molecule-1 as an early predictor of hepatic failure in patients with septic shock.

OBJECTIVE: To investigate whether endotoxin, interleukin-6, and circulating adhesion molecules, measured sequentially in blood, can predict mortality and organ dysfunction in sepsis. DESIGN: Inception cohort study with follow-up for 28 days. SETTING: Surgical intensive care unit at a university hospital. PATIENTS: A total of 14 consecutive patients were enrolled in the study within the first 24 hrs after onset of septic shock. Seven healthy subjects were studied as controls. INTERVENTIONS: Patients were analyzed for mortality and development of organ dysfunction. MEASUREMENTS AND MAIN RESULTS: At the end of the 28-day follow-up period, seven of the patients were still alive (survivors) but the other seven (nonsurvivors) had died. At the time of enrollment in the study (day 0), the Acute Physiology and Chronic Health Evaluation II score was 28.4 in survivors (n = 7) and 28.7 in nonsurvivors (n = 7). In contrast, circulating intercellular adhesion molecule-1 (ICAM-1) was significantly higher in nonsurvivors than in survivors. Circulating ICAM-1 predicted mortality in patients with septic shock with a sensitivity and a specificity of 71.4% each. Endotoxin, interleukin-6, circulating L-selectin, P-selectin, E-selectin, and platelet endothelial cell adhesion molecule-1, however, did not distinguish between survivors and nonsurvivors. In addition, circulating ICAM-1 at day 0 showed a significant correlation with the highest serum bilirubin observed during the entire study period (r2 = 0.963). CONCLUSIONS: Because only circulating ICAM-1 was higher in nonsurvivors than in survivors at day 0, circulating ICAM-1 may serve as an early prognostic marker for outcome in septic shock. In addition, measurement of circulating ICAM-1 facilitates identification of those patients with the highest risk of developing liver dysfunction.

APACHE↗

Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.

The crystal structure of the FMN-binding domain of human NADPH-cytochrome P450 reductase (P450R-FMN), a key component in the cytochrome P450 monooxygenase system, has been determined to 1.93 A resolution and shown to be very similar both to the global fold in solution (Barsukov I et al., 1997, J Biomol NMR 10:63-75) and to the corresponding domain in the 2.6 A crystal structure of intact rat P450R (Wang M et al., 1997, Proc Nat Acad Sci USA 94:8411-8416). The crystal structure of P450R-FMN reported here confirms the overall similarity of its alpha-beta-alpha architecture to that of the bacterial flavodoxins, but reveals differences in the position, number, and length of the helices relative to the central beta-sheet. The marked similarity between P450R-FMN and flavodoxins in the interactions between the FMN and the protein, indicate a striking evolutionary conservation of the FMN binding site. The P450R-FMN molecule has an unusual surface charge distribution, leading to a very strong dipole, which may be involved in docking cytochrome P450 into place for electron transfer near the FMN. Several acidic residues near the FMN are identified by mutagenesis experiments to be important for electron transfer to P4502D6 and to cytochrome c, a clear indication of the part of the molecular surface that is likely to be involved in substrate binding. Somewhat different parts are found to be involved in binding cytochrome P450 and cytochrome c.

Animals↗