Biomedical subjects

D Yao

Publications and source records attributed to D Yao.

At least 19 recordsLinked to original sources

PubMed2003

Development of a two-stage flexible fibre biofilm reactor for treatment of food processing wastewater.

Biofilm (or attached growth) reactors can be effectively used to treat organic wastewater from various industries such as food processing industry. They have a number of advantages including high organic loading rates (OLRs) and improved operational stability. A flexible fibre biofim reactor (FFBR) has been developed for efficient and cost effective treatment of food processing wastewater. In the process, simple flexible fibre packing with a very high specific surface area is used as support for microorganisms. The COD removal efficiencies for a range of OLRs have been studied. The FFBR can support an increasingly high OLR, but with a corresponding decrease in the COD removal efficiency. Therefore, a two-stage FFBR was developed to increase the treatment efficiency for systems with high OLRs. Experimental results indicated that a high overall COD removal efficiency could be achieved. At an influent COD of about 2700 mg/L and an OLR of 7.7 kgCOD/m3d, COD removal efficiencies of 76% and 82% were achieved in the first and the second stage of the reactor, respectively. The overall COD removal efficiency was 96%. Therefore, even for wastewater samples with high organic strength, high quality treated effluents could be readily achieved by the use of multiple stage FFBRs.

Biofilms↗

PubMed2002

An equivalent current source model and laplacian weighted minimum norm current estimates of brain electrical activity.

We have developed a method for estimating the three-dimensional distribution of equivalent current sources inside the brain from scalp potentials. Laplacian weighted minimum norm algorithm has been used in the present study to estimate the inverse solutions. A three-concentric-sphere inhomogeneous head model was used to represent the head volume conductor. A closed-form solution of the electrical potential over the scalp and inside the brain due to a point current source was developed for the three-concentric-sphere inhomogeneous head model. Computer simulation studies were conducted to validate the proposed equivalent current source imaging. Assuming source configurations as either multiple dipoles or point current sources/sinks, in computer simulations we used our method to reconstruct these sources, and compared with the equivalent dipole source imaging. Human experimental studies were also conducted and the equivalent current source imaging was performed on the visual evoked potential data. These results highlight the advantages of the equivalent current source imaging and suggest that it may become an alternative approach to imaging spatially distributed current sources-sinks in the brain and other organ systems.

Algorithms↗

PubMed2001

Detection of leukemic cells in the CD34(+)CD38(-) bone marrow progenitor population in children with acute lymphoblastic leukemia.

Successful autologous hematopoietic stem cell (HSC) transplantation in childhood acute lymphoblastic leukemia (ALL) requires the ability to either selectively kill the leukemia cells or separate normal from leukemic HSC. Based on previous studies showing that more than 95% of childhood B-lineage ALL express CD38, this study evaluated whether normal CD34(+)CD38(-) progenitors from children with B-lineage ALL could be isolated by flow cytometry. CD34(+) cells from bone marrow samples from 10 children with B-lineage ALL were isolated at day 28 of treatment, when clinical remission had been attained. The CD34(+) progenitor cells were flow cytometrically sorted into CD34(+)CD38(+) and CD34(+)CD38(-) populations. The absolute numbers of CD34(+)CD38(-) cells that could be isolated ranged from 401 to 6245. The cells were then analyzed for the presence of clonotypic rearrangements of the T-cell receptor (TCR) Vdelta2-Ddelta3 locus. Only patients whose diagnostic marrow had an informative TCR Vdelta2-Ddelta3 rearrangement were included in this study. Detection thresholds were typically 10(-4) to 10(-5) leukemic cells in normal marrow. In 6 of 10 samples analyzed, the sorted CD34(+)CD38(-) cells had no detectable Vdelta2-Ddelta3 rearrangements. In 4 cases, the clonotypic leukemic Vdelta2-Ddelta3 rearrangement was detected in the CD34(+)CD38(-) population, indicating that the putative normal HSC population also contained leukemic cells. The data indicate that although most childhood ALL cells express CD34 and CD38, leukemic cells are also frequently present in the CD34(+)CD38(-) population. Therefore, strategies to isolate and transplant normal HSC from children with ALL will require a more stringent definition of the normal HSC than the CD34(+)CD38(-) phenotype. (Blood. 2001;97:3925-3930)

ADP-ribosyl Cyclase↗

PubMed2001

Human NADPH-P450 oxidoreductase modulates the level of cytochrome P450 CYP2D6 holoprotein via haem oxygenase-dependent and -independent pathways.

NADPH-P450 oxidoreductase (CPR) is essential for the activity of cytochrome P450 (P450). Previous studies demonstrated that CPR regulates the levels of various P450 isoforms in vitro. We investigated the mechanistic basis for this regulation. By transfection of Chinese hamster ovary DUKXB11 cells we obtained the cell line DUKX/2D6, which expressed human CYP2D6, a P450 isoform. Subsequently, DUKX/2D6 cells were transfected with human CPR cDNA to generate the cell line DUKX/2D6/CPR-3. Expression of recombinant CPR decreased the level of spectrally detectable CYP2D6 holoprotein in DUKX/2D6/CPR-3 cells by 70%, whereas the level of immunodetectable apoprotein remained unchanged. Addition of the radical scavenger DMSO increased levels of CYP2D6 holoenzyme in DUKX/2D6/CPR-3 cells but not in DUKX/2D6 cells. A similar effect was noted when cells were grown in the presence of hemin. Importantly, combined treatment with DMSO and hemin increased levels of CYP2D6 holoenzyme in DUKX/2D6/CPR-3 but not in DUKX/2D6 cells even further than either treatment alone. None of these treatments affected the level of immunodetectable CYP2D6. This demonstrates that expression of CPR increases production of damaging radicals but also that CPR may alter haem homoeostasis. In agreement with this, the activity of haem oxygenase, a rate-limiting enzyme in haem metabolism, was compared with that in DUKX/DHFR control cells (expressing dihydrofolate reductase), and was 3-fold higher in DUKX/2D6/CPR-3 but similar in DUKX/2D6 cells. Furthermore, treatment of cells with sodium arsenite increased levels of haem oxygenase concomitant with a marked decrease of spectrally detectable CYP2D6 and a rise in levels of ferritin, which sequesters free iron released from the destruction of haem. These data demonstrate that CPR regulates P450 activity by supplying electrons and also by altering P450 levels via radical-and haem oxygenase-mediated pathways.

Animals↗

PubMed2001

[Prolapse of the urethral mucosa in young girls from the Ivory Coast].

In this retrospective study covering a nine-year period, 65 cases have been analyzed of prolapse of the urethral mucosa in young girls (aged between six weeks and 14 years) from the Ivory Coast. The aim of this study was to describe the etiology of this disorder, and to demonstrate the utility of ambulatory surgery. The main reason for the detection of this disorder was mild genital hemorrhage in 37 cases, which was related to rape in eight instances and to other types of trauma in nine cases, thereby raising serious medico-legal problems. Various forms of treatment were used (medical and/or surgical). The medical approach consisted of antibiotic and antiinflammatory treatment, combined with a local antiseptic. Two surgical approaches were adopted, either the Doria method in which the necrosed tissue is spontaneously eliminated after three to five days, or surgical excision under general anesthesia of the prolapsed mucosa followed by seromucosal stitching. The results were satisfactory in all cases, and in the surgically operated cases no complications or recurrence were noted at one-year follow-up.

Adolescent↗

PubMed2001

Synthesis and reactivity of the catechol metabolites from the equine estrogen, 8,9-dehydroestrone.

The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with an increased cancer risk. Previously, we showed that the equine estrogens equilin and equilenin, which are major components of the widely prescribed estrogen replacement formulation Premarin, are metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. Chem. Res. Toxicol. 1998, 11, 1113-1127]. In this study, we have synthesized 8,9-dehydroestrone (a third equine estrogen component of Premarin) and its potential catechol metabolites, 4-hydroxy-8,9-dehydroestrone and 2-hydroxy-8,9-dehydroestrone. Both 2-hydroxy-8,9-dehydroestrone and 4-hydroxy-8,9-dehydroestrone were oxidized by tyrosinase or rat liver microsomes to o-quinones which reacted with GSH to give one mono-GSH conjugate and two di-GSH conjugates. Like endogenous estrogens, 8,9-dehydroestrone was primarily converted by rat liver microsomes to the 2-hydroxylated rather than the 4-hydroxylated o-quinone GSH conjugates; the ratio of 2-hydroxy-8,9-dehydroestrone versus 4-hydroxy-8,9-dehydroestrone was 6:1. Also in contrast to experiments with equilin, 4-hydroxyequilenin was not observed in microsomal incubations with 8,9-dehydroestrone or its catechols. The behavior of 2-hydroxy-8,9-dehydroestrone was found to be more complex than 4-hydroxy-8,9-dehydroestrone as GSH conjugates resulting from 2-hydroxy-8,9-dehydroestrone were detected even without oxidative enzyme catalysis. Under physiological conditions, 2-hydroxy-8,9-dehydroestrone isomerized to 2-hydroxyequilenin to form the very stable 2-hydroxyequilenin catechol; however, 4-hydroxy-8,9-dehydroestrone was found to be stable under similar conditions. Finally, preliminary studies conducted with the human breast tumor S-30 cell lines demonstrated that the catechol metabolites of 8,9-dehydroestrone were much less toxic than 4-hydroxyequilenin (20-40-fold). These results suggest that the catechol metabolites of 8,9-dehydroestrone may have the ability to cause cytotoxicity in vivo primarily through formation of o-quinones; however, most of the adverse effects of Premarin estrogens are likely due to formation of 4-hydroxyequilenin o-quinone from equilin and equilenin.

Animals↗

PubMed2001

Synthesis and reactivity of potential toxic metabolites of tamoxifen analogues: droloxifene and toremifene o-quinones.

Tamoxifen remains the endocrine therapy of choice in the treatment of all stages of hormone-dependent breast cancer. However, tamoxifen has been shown to increase the risk of endometrial cancer which has stimulated research for new effective antiestrogens, such as droloxifene and toremifene. In this study, the potential for these compounds to cause cytotoxic effects was investigated. One potential cytotoxic mechanism could involve metabolism of droloxifene and toremifene to catechols, followed by oxidation to reactive o-quinones. Another cytotoxic pathway could involve the oxidation of 4-hydroxytoremifene to an electrophilic quinone methide. Comparison of the amounts of GSH conjugates formed from 4-hydroxytamoxifen, droloxifene, and 4-hydroxytoremifene suggested that 4-hydroxytoremifene is more effective at formation of a quinone methide. However, all three substrates formed similar amounts of o-quinones. Both the tamoxifen-o-quinone and toremifene-o-quinone reacted with deoxynucleosides to give corresponding adducts. However, the toremifene-o-quinone was shown to be considerably more reactive than the tamoxifen-o-quinone in terms of both kinetic data as well as the yield and type of deoxynucleoside adducts formed. Since thymidine formed the most abundant adducts with the toremifene-o-quinone, sufficient material was obtained for characterization by (1)H NMR, COSY-NMR, DEPT-NMR, and tandem mass spectrometry. Cytotoxicity studies with tamoxifen, droloxifene, 4-hydroxytamoxifen, 4-hydroxytoremifene, and their catechol metabolites were carried out in the human breast cancer cell lines S30 and MDA-MB-231. All of the metabolites tested showed cytotoxic effects that were similar to the parent antiestrogens which suggests that o-quinone formation from tamoxifen, droloxifene, and 4-hydroxytoremifene is unlikely to contribute to their cytotoxicity. However, the fact that the o-quinones formed adducts with deoxynucleosides in vitro implies that the o-quinone pathway might contribute to the genotoxicity of the antiestrogens in vivo.

Animals↗

PubMed2001

Source potential mapping: a new modality to image neural electric activities.

A new neural electric imaging modality-source potential mapping (SPM)-is presented here, which images the neural sources by the potential produced by the sources in a homogeneous infinite conducting medium. Compared with the extant cortical surface potential mapping (CPM). SPM is a more direct reflection of the sources and is a simpler physical model, thus assuring easy understanding. The simulations show that SPM has a slightly higher spatial resolution than CPM and the calculation of SPM is more economical than that of CPM.

Biomedical Engineering↗

PubMed2001

A study of equivalent source techniques for high-resolution EEG imaging.

High-resolution EEG imaging has been an important topic in recent EEG research, and much work has been done on the two equivalent source imaging techniques: the equivalent distributed dipole-layer source imaging technique (EST) and the equivalent multipole source imaging technique (SAT). In this paper we first develop a forward density formula for a spherical equivalent distributed dipole layer of an arbitrary dipole in a three-concentric-sphere head model. It is clarified using the derived forward formula that the equivalent dipole-layer source and equivalent multipole source are interrelated in theory. Finally, simulation comparisons are conducted, the results of which suggest that EST has a higher spatial resolution than SAT when both of them are implemented by a truncated singular value decomposition algorithm. This is due to the different singularities of the inversion equations involved in the two techniques. An empirical VEP data study also shows that EST is better than SAT in providing higher spatial resolution EEG imaging.

Cerebral Cortex↗

PubMed2001

A method to standardize a reference of scalp EEG recordings to a point at infinity.

The effect of an active reference in EEG recording is one of the oldest technical problems in EEG practice. In this paper, a method is proposed to approximately standardize the reference of scalp EEG recordings to a point at infinity. This method is based on the fact that the use of scalp potentials to determine the neural electrical activities or their equivalent sources does not depend on the reference, so we may approximately reconstruct the equivalent sources from scalp EEG recordings with a scalp point or average reference. Then the potentials referenced at infinity are approximately reconstructed from the equivalent sources. As a point at infinity is far from all the possible neural sources, this method may be considered as a reference electrode standardization technique (REST). The simulation studies performed with assumed neural sources included effects of electrode number, volume conductor model and noise on the performance of REST, and the significance of REST in EEG temporal analysis. The results showed that REST is potentially very effective for the most important superficial cortical region and the standardization could be especially important in recovering the temporal information of EEG recordings.

Algorithms↗

PubMed2001

Mechanisms of transforming growth factor-beta receptor endocytosis and intracellular sorting differ between fibroblasts and epithelial cells.

Transforming growth factor-betas (TGF-beta) are multifunctional proteins capable of either stimulating or inhibiting mitosis, depending on the cell type. These diverse cellular responses are caused by stimulating a single receptor complex composed of type I and type II receptors. Using a chimeric receptor model where the granulocyte/monocyte colony-stimulating factor receptor ligand binding domains are fused to the transmembrane and cytoplasmic signaling domains of the TGF-beta type I and II receptors, we wished to describe the role(s) of specific amino acid residues in regulating ligand-mediated endocytosis and signaling in fibroblasts and epithelial cells. Specific point mutations were introduced at Y182, T200, and Y249 of the type I receptor and K277 and P525 of the type II receptor. Mutation of either Y182 or Y249, residues within two putative consensus tyrosine-based internalization motifs, had no effect on endocytosis or signaling. This is in contrast to mutation of T200 to valine, which resulted in ablation of signaling in both cell types, while only abolishing receptor down-regulation in fibroblasts. Moreover, in the absence of ligand, both fibroblasts and epithelial cells constitutively internalize and recycle the TGF-beta receptor complex back to the plasma membrane. The data indicate fundamental differences between mesenchymal and epithelial cells in endocytic sorting and suggest that ligand binding diverts heteromeric receptors from the default recycling pool to a pathway mediating receptor down-regulation and signaling.

3T3 Cells↗

PubMed2001

Transforming growth factor beta receptor signaling and endocytosis are linked through a COOH terminal activation motif in the type I receptor.

Transforming growth factor beta (TGF-beta) coordinates a number of biological events important in normal and pathophysiological growth. In this study, deletion and substitution mutations were used to identify receptor motifs modulating TGF-beta receptor activity. Initial experiments indicated that a COOH-terminal sequence between amino acids 482-491 in the kinase domain of the type I receptor was required for ligand-induced receptor signaling and down-regulation. These 10 amino acids are highly conserved in mammalian, Xenopus, and Drosophila type I receptors. Although mutation or deletion of the region (referred to as the NANDOR BOX, for nonactivating non-down-regulating) abolishes TGF-beta-dependent mitogenesis, transcriptional activity, type I receptor phosphorylation, and down-regulation in mesenchymal cultures, adjacent mutations also within the kinase domain are without effect. Moreover, a kinase-defective type I receptor can functionally complement a mutant BOX expressing type I receptor, documenting that when the BOX mutant is activated, it has kinase activity. These results indicate that the sequence between 482 and 491 in the type I receptor provides a critical function regulating activation of the TGF-beta receptor complex.

Amino Acid Motifs↗

PubMed2001

A self-coherence enhancement algorithm and its application to enhancing three-dimensional source estimation from EEGs.

In this paper a new algorithm is proposed to enhance the spatial resolution of solutions of the underdetermined EEG inverse problem. Termed the self-coherence enhancement algorithm (SCEA), the present algorithm provides a self-coherence solution, which is a function of the high order self-coherence estimate of an unbiased smooth estimate of the underdetermined EEG inverse solution. The order of the high order self-coherence function is determined by the blurring level of the actual source distribution as represented by a normalized blurring index. The proposed SCEA algorithm may be used to enhance the spatial resolution of an inverse solution obtained by any inverse reconstruction algorithm. Computer simulation studies have been conducted to evaluate the performance of the SCEA and to compare its performance to that of the LORETA and the FOCUSS algorithms.

Algorithms↗

PubMed2001

Modulation of P450 CYP3A4-dependent metabolism by P-glycoprotein: implications for P450 phenotyping.

Some compounds used for phenotyping of cytochrome P450s are substrates of P-glycoprotein (pgp). It is likely that in these cases, the level of pgp modulates the metabolism of in vivo probes. To address this important issue, we have analyzed the effects of pgp on CYP3A4-mediated reactions in two newly established cell lines (3A4/HR/MDR(-) and 3A4/HR/MDR(+)), which express CYP3A4 in the absence and presence of pgp, respectively. In cultured cells, the presence of pgp increased the apparent K(m) for the 6beta-hydroxylase activity of CYP3A4 toward testosterone and cortisol by a factor of 1.7 and 4, respectively. These steroids are poor and good substrates of pgp, respectively, and cortisol 6beta-hydroxylase has been frequently used as an in vivo probe for CYP3A4. Interestingly, we also found that pgp modulated the inhibition of CYP3A4-mediated metabolism by several compounds in intact cells. Although quinidine inhibited testosterone 6beta-hydroxylase activity in membranes or in intact cells that expressed recombinant CYP3A4 in the absence of pgp, low concentrations of this compound increased CYP3A4 activity in intact cells that expressed pgp. These results imply that pharmacokinetic drug-drug interactions involving CYP3A4 can be influenced by pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

5-hydroxytryptamine3 (5-HT3) receptors mediate spinal 5-HT antinociception: an antisense approach.

To examine the role of the 5-hydroxytryptamine(1B) (5-HT1B) and 5-HT3 receptor subtypes in the analgesia produced by 5-HT (serotonin) agonists, we assessed the effect of antisense oligodeoxynucleotides (AODNs) designed to "knock down" the number of these receptor subtypes on analgesia produced by intrathecal (i.t.) 5-HT, the 5-HT1B receptor agonist, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate (CGS-12066A), and the 5-HT3 receptor agonist, 2-methyl-5-HT. Groups of mice (n = 17-20) were injected i.t. on days 1, 3, and 5 with one of the AODNs, a mismatch oligo, or saline. On day 6, all mice were injected i.t. with 70.5 nmol of 5-HT, 44.4 nmol of CGS-12066A, or 49 nmol of 2-methyl-5-HT by lumbar puncture. Following testing, spinal cords were rapidly removed and prepared for receptor binding assays. Treatment with AODN for 5-HT1B receptors produced a 70% reduction in ligand binding to this receptor subtype. After treatment with AODN for 5-HT3 receptors, ligand binding to this receptor subtype was undetectable. In mice tested with i.t. 5-HT, tail-flick analgesia was attenuated only in mice treated with the 5-HT3 receptor AODN. Mice treated with the AODN designed to knock down 5-HT(1B) receptors or with its mismatch oligo were not significantly different from controls. In mice tested with i.t. administration of CGS-12066A, none of the oligo treatments produced a significant attenuation of analgesia. In mice tested with i.t. administration of 2-methyl-5-HT, only 5-HT3 receptor AODN attenuated analgesia. Thus, 5-HT and 2-methyl-5-HT analgesia are mediated by the 5-HT3 receptor subtype. However, spinal CGS-12066A analgesia appears not to be mediated by either the 5-HT1B or the 5-HT3 receptor subtypes.

Animals↗

PubMed2001

[An off site petroleum-contaminated soil bioremediation technology: soil compositing in windrow].

With off-site bioremediation technology, a soil contaminated by crude oil from Liaohe Oil Field was treated on a 20 x 10 m prepared bed. 8 composting windrow units were set, each measured 8 m in length, 2 m in width, and 0.35 m in height. The results showed that when the pollutant petroleum hydrocarbon(TPH) was within the range of 4.16-7.72 g.100 g-1 soil, the total degradation rate of TPH reached 45.19%-56.74% after 53 days operation, which indicated that a technological basis would be provided for the bioremediation of oil-contaminated soil.

Biodegradation, Environmental↗

PubMed2001

An epidemiological survey on neonatal jaundice in China.

OBJECTIVE: To provide epidemiological data for revising the diagnostic criteria of neonatal hyperbilirubinemia in China. METHODS: A survey was performed among full-term infants in multiple centers throughout the country. From less than 24 hours after birth, the infants' bilirubin levels were measured every day until the peak level fell to less than 68.4 mumol/L. Auditory brainstem responses were assessed in 56 infants randomly chosen from those with serum bilirubin levels of higher than 220.5 mumol/L. RESULTS: Jaundice in most infants was detected at 2-3 days after birth. The bilirubin level usually reached a peak level of 204 +/- 54.69 mumol/L at 5 days after birth and then fell. Among the 875 infants, the serum bilirubin levels in 34.4% of neonates were higher than 220.5 mumol/L. The mean serum bilirubin level of the infants during the first week after birth varied with geography (P < 0.001) and season (P < 0.001). The serum bilirubin level was significantly associated with gestation age (P < 0.01), delivery method (P < 0.01), weight loss (P < 0.001), and PCV elevation (P < 0.001) during the first three days after birth. CONCLUSIONS: The start time of neonatal jaundice was similar to that reported elsewhere, but the mean peak level in our study was higher than the reported. It is suggested that the diagnostic criteria for neonatal hyperbilirubinemia in China should be strict.

Bilirubin↗

PubMed2001

[Influence of heart position change on body surface potential distribution].

Based on a 3-D emulational body torso model, the influence of changes of heart position caused by deep inspiration etc. on body surface potential maps(BSPMs) was studied in forward electrocardiography. In this report, BSPMs and ECGs during QRS were provided while the heart was in the normal position, or rotated clockwise to the vertical or counterclockwise to the transverse.

Algorithms↗