Biomedical subjects

Q Zhao

Publications and source records attributed to Q Zhao.

At least 55 records · Page 3Linked to original sources

PubMed2001

Nuclear stopping as a probe for in-medium nucleon-nucleon cross sections in intermediate energy heavy ion collisions.

Using an isospin-dependent quantum molecular dynamics, nuclear stopping in intermediate heavy ion collisions has been studied. The calculation has been done for colliding systems with different neutron-proton ratios in beam energy ranging from 15 MeV/ u to 150 MeV/ u. It is found that, in the energy region from above Fermi energy to 150 MeV/ u, nuclear stopping is very sensitive to the isospin dependence of in-medium nucleon-nucleon cross section, but insensitive to symmetry potential. From this investigation, we propose that nuclear stopping can be used as a new probe to extract the information on the isospin dependence of in-medium nucleon-nucleon cross section in intermediate energy heavy ion collisions.

Journal Article↗

PubMed2001

Soluble recombinant endostatin purified from Escherichia coli: antiangiogenic activity and antitumor effect.

Endostatin is a potent and specific antiangiogenic protein capable of inhibiting the growth of murine and xenotransplanted human tumors. Thus far, however, recombinant endostatin prepared from Escherichia coli is insoluble after purification and therefore inappropriate for clinical settings. A soluble form of endostatin is available from a yeast system with relatively low yield and high cost, which has made it difficult to produce endostatin in quantities sufficient for extensive clinical evaluation. In this study, we developed a protocol to generate soluble recombinant murine endostatin from E. coli at a yield of 150 mg/liter-culture and 99% purity. The in vivo antiangiogenic and antitumor activities of the soluble recombinant endostatin are equally as potent as those of the previously published insoluble form. A similar protocol may be used to produce soluble human endostatin.

Angiogenesis Inhibitors↗

PubMed2001

Biogenesis of lysosomes in marshall cells and in cells of the male reproductive system.

UNLABELLED: The mechanism of plasma membrane trafficking and degradation is still poorly understood. This investigation deals with the biogenesis of lysosomes during endocytic flow in Marshall cells and in various cell types of the male reproductive system. Marshall cells were exposed to ammonium chloride (NH4Cl) and leupeptin after labeling with cationic ferritin. In some experiments, the treated cells were immunogold labeled with anti-prosaposin antibody. NH4Cl and leupeptin are lysosomotropic agents that affect the endosomal-lysosomal progression. Testes, efferent ducts and epididymis from mouse mutants with defects affecting plasma membrane degradation were also used to analyze this process. NH4Cl produced a retention of cationic ferritin in endosomes and hindered the endosomal/lysosomal progression. Leupeptin did not affect this process. NH4Cl decreased the labeling of prosaposin in endosomes and lysosomes, while leupeptin increased the labeling of prosaposin in lysosomes. The number of lysosomes per cytoplasmic area was higher in treated cells than in controls. These findings suggest that leupeptin affected lysosomes whereas NH4Cl affected both endosomes and lysosomes. The endosomal and lysosomal accumulation of prosaposin induced by the treatment with NH4Cl and leupeptin indicated that the site of entry of prosaposinwas both the lysosome and endosome. Electron microscopy (EM) of tissues from mouse mutants with defects affecting plasma membrane degradation substantiated these observations. The EM analysis revealed a selective accumulation of multivesicular bodies (MVBs) and the disappearance of lysosomes, in testicular fibroblasts, nonciliated cells of the efferent ducts and principal cells of the epididymis, suggesting that MVBs are precursors of lysosomes. IN CONCLUSION: (1) endosomes and MVBs are a required steps for degradation of membranes; (2) endosomes and MVBs are precursors of lysosomes; and (3) endosomes, MVBs, and lysosomes appear to be transient organelles.

Ammonium Chloride↗

PubMed2001

Study of laser vas deferens occlusion.

The objective of this study was to determine threshold levels for high-power laser output Nd:YAG laser photocoagulation and to determine the possible reversibility of laser vas occlusion. The study included vas deferens of 220 rabbits and 20 samples of men in vitro, applying the Nd:YAG laser instrument, doing vasopuncture by a catheter needle, guiding the fiber into the vas, and performing the irradiation occlusion experiment to determine effective threshold value of photocoagulation. The effect and safety of occlusion were followed-up over a year, and reopening a experiment was done in 60 occluded nodes of rabbits. The postoperative sperm disappearance rate was 100%, and reopening rate was 72.7% without obvious complications. High-power lasers may be used as photocoagulation, and its merits are reliable, effective, and rapid recovery. The vas threshold lesion value of rabbits and men in vitro are 50 W/0.5 s, 45 W/1 s, respectively, and irradiation depth reached the middle-ring muscularis.

Animals↗

PubMed2001

Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationships.

Oligodeoxynucleotides containing unmethylated CpG-motifs stimulate the innate immune system, including inducing B-cell proliferation and cytokine production. However, the mechanism of immunostimulation by CpG-oligonucleotides and the precise structural requirements and specific functional groups of cytosine and guanine necessary for recognition of and interaction with protein/receptor factors that are responsible for immune stimulation have not been elucidated. We sought to understand the critical role of each functional group of the cytosine and guanine moieties in a CpG-motif in inducing immunostimulatory activity. To this end, we examined structure-immunostimulatory activity relationships of phosphorothioate oligodeoxynucleotides (PS-oligos) containing YpG- and CpR-motifs (Y and R stand for pyrimidine and purine analogues, respectively). The PS-oligos containing a YpG-motif in which the natural deoxycytidine was replaced with deoxy-5-hydroxycytidine or deoxy-N4-ethylcytidine showed immunostimulatory activity. Substitution of deoxycytidine with a deoxy-5-methylisocytidine, deoxyuridine, or deoxy-P-base-nucleoside in the YpG-motif completely abolished the immunostimulatory activity, similar to the results observed with deoxy-5-methylcytidine. In the case of PS-oligos containing a CpR-motif, 7-deazaguanine substitution for natural guanine showed immunostimulatory activity similar to that of a parent PS-oligo. These studies suggest that the 2-keto, 3-imino and 4-amino groups of cytosine, and the 1-imino, 2-amino and 6-keto groups of guanine in a CpG-motif are important for the immunostimulatory activity of CpG-PS-oligos. The absence of N7 on guanine of the CpG-motif does not affect immunostimulatory activity significantly. These studies suggest that it is possible to develop YpG- and CpR-motifs as an alternative to CpG-motifs in PS-oligos for immunostimulatory studies.

Animals↗

PubMed2001

Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkages.

Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG-motifs in a particular sequence context activate vertebrate immune cells. We examined the significance of negatively charged internucleoside linkages in the flanking sequences 5' and 3' to the CpG-motif on immunostimulatory activity. Cell proliferation and secretion of IL-12 and IL-6 in mouse spleen cell cultures, and spleen weights of mice increased significantly when a non-ionic linkage was placed at least four or more internucleoside linkages away from the CpG-motif in the 5'-flanking sequence. When the non-ionic linkage was placed closer than three internucleoside linkages in the 5'-flanking sequence to the CpG-motif, immunostimulatory activity was suppressed compared with that observed with the unmodified parent oligo. In general, the placement of non-ionic linkage in the 3'-flanking sequence to the CpG-motif either did not affect or slightly increased immunostimulatory activity compared with the parent oligo. These results have significance in understanding CpG oligonucleotide-receptor interactions and the development of potent immunomodulatory agents.

Adjuvants, Immunologic↗

PubMed2001

Rab3a and SNARE proteins: potential regulators of melanosome movement.

Melanosomes are specialized organelles that undergo a dynamic process of transport along the melanocyte dendrite to the dendrite tip and transfer to keratinocytes. We hypothesized that soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE), which are involved in membrane fusion, and rab3a, a GTP-binding protein involved in exocytosis in neuronal cells and in SNARE complex assembly, may play a part in melanosome transport and transfer. By reverse transcription-polymerase chain reaction we identified transcripts for rab3a, vesicle-associated membrane protein-2, synaptosome-associated proteins of 23 kDa and 25 kDa, and syntaxin-4 in murine melanocytic cells. We also showed that purified melanosome preparations contain rab3a and SNARE, including vesicle-associated membrane protein-2, syntaxin-4, synaptosome-associated proteins 23 kDa and 25 kDa, and the SNARE accessory protein, alpha-soluble N-ethylmaleimide-sensitive factor attachment protein. Ultraviolet radiation is a potent stimulus for melanosome transport and transfer. We show that ultraviolet radiation rapidly suppresses melanosome-associated rab3a expression and that this occurs at the protein and mRNA level. Finally, we show that vesicle-associated membrane protein-2 and synaptosome-associated protein 23 kDa coimmunoprecipitate from purified melanocytic cell membranes, suggesting that they form complexes. The presence of rab3a and SNARE on melanosomes, and of SNARE complexes in melanocytic cell membranes suggests that these proteins play a part in targeting melanosomes to the plasma membrane, to melanosome transfer to keratinocytes, or both.

Animals↗

PubMed2001

Effects of gradual bone lengthening on the rabbit tibial nerve.

Little is known about the effect of gradual bone lengthening on peripheral nerves. In the present study, an external fixation device was applied to the rabbit tibia, which was then divided. After seven days, the tibia was subjected to 0.7 mm/day callus distraction for periods of up to one month. The tibial nerve was fixed in glutaraldehyde and plastic sections were cut in longitudinal and transverse planes for light and electron microscopy. Light microscopy showed a 64% increase in the gap length at the node of Ranvier in myelinated axons from the experimental side compared with the control side. The cross-sectional area of the non-myelinated axons was not altered significantly. We conclude that gradual stretching of the nerve elongates the nerve fibres at least at the region of the nodes, perhaps a point of least resistance. Diameters of fibres seem to be held more constant during the lengthening procedure.

Animals↗

PubMed2001

Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: effect of lead exposure.

Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives of this study were to establish in humans whether TTR and thyroxine (T(4)) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T(4), and/or retinol-binding protein (RBP). Eighty-two paired CSF and blood/serum samples were collected from patients undergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 +/- 1.60 microg/mg of CSF proteins (mean +/- SD, n = 82), for total T(4) (TT(4)) was 1.56 +/- 1.68 ng/mg (n = 82), for RBP was 0.34 +/- 0.19 microg/mg (n = 82), and for Pb was 0.53 +/- 0.69 microg/dl (n = 61 for those above the detection limit). Linear regression analyses revealed that CSF TTR levels were positively associated with those of CSF TT(4) (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb concentrations (r = -0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF TT(4) and CSF Pb concentrations (r = -0.22, p = 0.09). The concentrations of TTR, TT(4), and Pb in the CSF did not vary as the function of their levels in blood or serum, but RBP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by PB: These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF.

Adolescent↗

PubMed2001

Applications of mechanistic data in risk assessment: the past, present, and future.

Mechanistic data, when available, have long been considered in risk assessment, such as in the development of the nitrate RfD based on effects in a sensitive group (infants). Recent advances in biology and risk assessment methods have led to a tremendous increase in the use of mechanistic data in risk assessment. Toxicokinetic data can improve extrapolation from animals to humans and characterization of human variability. This is done by the development of improved tissue dosimetry, by the use of uncertainty factors based on chemical-specific data, and in the development of physiologically based pharmacokinetic (PBPK) models. The development of the boron RfD illustrates the use of chemical-specific data in the improved choice of uncertainty factors. The draft cancer guidelines of the U.S. Environmental Protection Agency emphasize the use of mode of action data. The first choice under the guidelines is to use a chemical-specific, biologically based dose-response (BBDR) model. In the absence of a BBDR model, mode of action data are used to determine whether low-dose extrapolation is done using a linear or nonlinear (margin of exposure) approach. Considerations involved in evaluating a hypothesized mode of action are illustrated using 1,3-dichloropropene, and use of a BBDR model is illustrated using formaldehyde. Recent developments in molecular biology, including transgenic animals, microarrays, and the characterization of genetic polymorphisms, have significant potential for improving risk assessments, although further methods development is needed. Overall, use of mechanistic data has significant potential for reducing the uncertainty in assessments, while at the same time highlighting the areas of uncertainty.

Allyl Compounds↗

PubMed2001

Determination of the detective quantum efficiency of a prototype, megavoltage indirect detection, active matrix flat-panel imager.

After years of aggressive development, active matrix flat-panel imagers (AMFPIs) have recently become commercially available for radiotherapy imaging. In this paper we report on a comprehensive evaluation of the signal and noise performance of a large-area prototype AMFPI specifically developed for this application. The imager is based on an array of 512 x 512 pixels incorporating amorphous silicon photodiodes and thin-film transistors offering a 26 x 26 cm2 active area at a pixel pitch of 508 microm. This indirect detection array was coupled to various x-ray converters consisting of a commercial phosphor screen (Lanex Fast B, Lanex Regular, or Lanex Fine) and a 1 mm thick copper plate. Performance of the imager in terms of measured sensitivity, modulation transfer function (MTF), noise power spectra (NPS), and detective quantum efficiency (DQE) is reported at beam energies of 6 and 15 MV and at doses of 1 and 2 monitor units (MU). In addition, calculations of system performance (NPS, DQE) based on cascaded-system formalism were reported and compared to empirical results. In these calculations, the Swank factor and spatial energy distributions of secondary electrons within the converter were modeled by means of EGS4 Monte Carlo simulations. Measured MTFs of the system show a weak dependence on screen type (i.e., thickness), which is partially due to the spreading of secondary radiation. Measured DQE was found to be independent of dose for the Fast B screen, implying that the imager is input-quantum-limited at 1 MU, even at an extended source-to-detector distance of 200 cm. The maximum DQE obtained is around 1%--a limit imposed by the low detection efficiency of the converter. For thinner phosphor screens, the DQE is lower due to their lower detection efficiencies. Finally, for the Fast B screen, good agreement between calculated and measured DQE was observed.

Biophysical Phenomena↗

PubMed2001

Pharmacokinetics of intravenous itraconazole followed by itraconazole oral solution in patients with human immunodeficiency virus infection.

This randomized, open-label, comparative study assessed the pharmacokinetics and safety of intravenous and oral hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solutions of itraconazole in patients with advanced human immunodeficiency virus (HIV) infection. All patients received 1-hour intravenous infusions of itraconazole 200 mg twice dailyfor 2 days, then once dailyfor 5 days. Patients were then randomized to receive itraconazole oral solution, 200 mg twice daily or 200 mg once daily, for a further 28 days. Itraconazole was solubilized by HP-beta-CD in both intravenous and oral solutions, so HP-beta-CD concentration in plasma was measured. Thirty-two patients were enrolled and analyzed (n = 32 for intravenous treatment, 32 completed; n = 16 for oral once daily, 15 completed; n = 16 for oral twice daily, 12 completed). Steady-state plasma concentrations of itraconazole and hydroxyitraconazole were reached by days 3 and 6, respectively. After intravenous dosing, mean trough plasma concentrations of itraconazole and hydroxyitraconazole were 906 ng/ml and 1,690 ng/ml, respectively. During oral dosing, mean trough plasma concentrations of itraconazole and hydroxyitraconazole were maintained or increased in the 200 mg twice-dailygroup but fell with the 200 mg once-daily oral dose. Itraconazole was generally well tolerated and had a favorable safetyprofile; minor changes in hematology variables were noted during the intravenous phase, and HP-beta-CD was cleared rapidly, mostly in urine. Twenty-eight patients (88%) experienced at least one adverse event; no adverse event was severe, and only seven were definitely related to itraconazole. In conclusion, itraconazole 200 mg given intravenously twice daily for 2 days, then once daily for 5 days, rapidly achieves amean steady-state trough concentration of itraconazole of over 250 ng/ml, which is associated with clinic outcome and is effectively maintained with itraconazole oral solution 200 mg twice daily in patients with advanced HIV infection.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2001

Effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils.

The effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils were studied. The histamine and H2 agonists impromidine and 4-methylhistamine caused concentration-related increases in the number of differentiated cells. On the other hand, the H1 agonists 2-methylhistamine and 2-pyndylethylamine showed no such effect. Histamine-induced eosinophil differentiation was antagonized by the H2 antagonists cimetidine and ranitidine. Histamine and H2 agonists inhibited (3H)-thymidine uptake, suggesting that these compounds caused a decrease in proliferation. Histamine as well as the H2 agonists impromidine and 4-methythistamine caused increases in cAMP level, and this effect was antagonized by ranitidine. From these findings, we concluded that both the differentiation of HL-60-Eo cells into eosinophils and proliferation of HL-60-Eo cells were mediated via H2 receptors.

Cell Differentiation↗

PubMed2001

Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice.

The experimental work characterizing the anabolic effect of parathyroid hormone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) animals, mainly rats. A major drawback of these animal models is their inaccessibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermittently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral bones were evaluated by microcomputed tomography (microCT) followed by histomorphometry. A tight correlation was observed between trabecular density (BV/TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. PTH induced a approximately 35% recovery of this loss and a approximately 40% reversal of the associated decreases in trabecular number (Tb.N) and connectivity. PTH also caused a shift from single to double calcein-labeled trabecular surfaces, a significant enhancement in the mineralizing perimeter and a respective 2- and 3-fold stimulation of the mineral appositional rate (MAR) and bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thickness also were increased with a high correlation between these parameters. These data show that OVX osteoporotic mice respond to PTH by increased osteoblast activity and the consequent restoration of trabecular network. The Swiss-Webster mouse model will be useful in future studies investigating molecular mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.

Animals↗

PubMed2001

Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers.

STUDY OBJECTIVE: To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men. DESIGN: Open-label, three-phase, sequential study. SETTING: Clinical research center. SUBJECTS: Twelve healthy male volunteers. INTERVENTIONS: Each subject was treated according to the following sequence: baseline; phase 1 (days 1-6): cisapride 10 mg 4 times/day; washout (days 7-13); phase 2 (days 14-44): fluoxetine 20 mg/day; and phase 3 (days 45-52): cisapride 10 mg 4 times/day (days 45-51) plus fluoxetine 20 mg/day (days 45-52). MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn and 12-lead electrocardiograms performed at specified time points after the last morning dose of cisapride in phases 1 and 3. Blood samples also were taken before morning doses on the 3rd, 4th, and 5th days of phases 1 and 3. Electrocardiograms were done at baseline and on the last day of the washout period and phase 2. Coadministration of fluoxetine significantly decreased cisapride plasma concentrations. There were no clinically significant changes in corrected QT intervals during administration of cisapride alone or with fluoxetine. Cisapride was well tolerated when administered alone or with fluoxetine. CONCLUSION: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.

Adolescent↗

PubMed2001

A comparative study on the viscoelasticity and morphology of polyaniline films galvanostatically grown on bare and 4-aminothiophenol-modified gold electrodes using an electrochemical quartz crystal impedance system and SEM.

The equivalent-circuit parameters of the 9-MHz piezoelectric quartz crystal (PQC) resonance were measured in situ during the galvanostatic polymerization of aniline on 4-aminothiophenol(4-ATP)-modified and bare Au electrodes for ca. 2000 s, respectively. Two polymerization media, 0.100 mol L-1 aniline in 1.0 mol L-1 H2SO4 and in 2.0 mol L-1 HClO4 aqueous solutions, and two values of the current density, 12 and 36 microA cm-2, were used. At identical levels of the resonant frequency shifts in the solutions, obviously greater increases in the motional resistance (R1) were found after aniline polymerization on bare Au electrodes, though the absolute values of delta f0/delta R1 were all large; also, the resonant frequency shifts in air (delta f0g) were considerably smaller for PANI films grown on bare Au electrodes. It is thus concluded that, under identical polymerization conditions, (1) the PANI film grown on a bare gold electrode is rougher, less compact, and can entrap solution more notably; (2) the deposition efficiency of PANI is higher on a 4-ATP-modified Au electrode, owing to a significantly greater observed "dry" frequency shift, and thus a greater "net" mass value of the polyaniline backbone. SEM observations have confirmed that PANI films on 4-ATP-modified Au electrodes were smoother and more compact than those grown on bare Au ones under identical polymerization conditions. In addition, a technique of simultaneous measurements of the electroacoustic admittance of the PQC resonance and the electrochemical impedance was used to monitor the adsorption of 4-ATP onto a PQC gold electrode.

Journal Article↗

PubMed2001

[Research progresses on degradation mechanism in vivo and medical applications of polylactic acid].

Polylactic acid (PLA), a kind of aliphatic polyester, is a biodegradable polymer with outstanding biocompatibility. The degradation of PLA is a complex process involving four main phenomena, namely water absorption, ester cleavage, diffusion of soluble oligomers, and solubilization of fragments. This paper emphasizes on the following aspects: 1) present understanding of the hydrolytic degradation and enzymatic degradation of PLA and autocatalystic degradation mechanism in the bulk PLA; 2) main factors influencing PLA degradation; 3) biological results; 4) the development in application of PLA.

Aerospace Medicine↗

PubMed2001

Effect of dl-praeruptorin A on ATP sensitive potassium channels in human cortical neurons.

AIM: To investigate the effect of dl-praeruptorin A (Pd-Ia) on ATP sensitive potassium channels (KATP channel) in human cortical neurons. METHODS: Using standard whole cell recording method. Cell membranes were held at -40 mV, commanding potential was -30 to +100 mV and duration was 600 ms. RESULTS: Pd-Ia activated KATP channels in human cortical neurons in a concentration-dependent manner. After consecutive perfusion with external solution containing Pd-Ia 0.001, 0.01, 0.1, and 1 micromol/L, currents increased from control (0.9 +/- 0.4) nA to (1.0 +/- 0.4) nA, (1.1 +/- 0.4) nA, (1.2 +/- 0.4) nA, and (1.3 +/- 0.4) nA (P < 0.05 or P < 0.01, n = 5) respectively. Then the current decreased to (0.90 +/- 0.37) nA (P < 0.01, n = 5) after washout with glibenclamide (10 micromol/L). The increscent part of the currents could nearly be inhibited by specific KATP channel inhibitor. CONCLUSION: Pd-Ia could open KATP channel and it is a kind of potassium channel opener

Adenosine Triphosphate↗