Biomedical subjects

Wei Qiu

Publications and source records attributed to Wei Qiu.

45 records · Page 3Linked to original sources

PubMed2003

The effects of the amplitude distribution of equal energy exposures on noise-induced hearing loss: the kurtosis metric.

Seventeen groups of chinchillas with 11 to 16 animals/group (sigmaN = 207) were exposed for 5 days to either a Gaussian (G) noise or 1 of 16 different non-Gaussian (non-G) noises at 100 dB(A) SPL. All exposures had the same total energy and approximately the same flat spectrum but their statistical properties were varied to yield a series of exposure conditions that varied across a continuum from G through various non-G conditions to pure impact noise exposures. The non-G character of the noise was produced by inserting high level transients (impacts or noise bursts) into the otherwise G noise. The peak SPL of the transients, their bandwidth, and the intertransient intervals were varied, as was the rms level of the G noise. The statistical metric, kurtosis (beta), computed on the unfiltered noise beta(t), was varied 3 < or = beta(t) < or = 105. Brainstem auditory evoked responses were used to estimate hearing thresholds and surface preparation histology was used to determine sensory cell loss. Trauma, as measured by asymptotic and permanent threshold shifts (ATS, PTS) and by sensory cell loss, was greater for all of the non-G exposure conditions. Permanent effects of the exposures increased as beta(t) increased and reached an asymptote at beta(t) approximately 40. For beta(t) > 40 varying the interval or peak histograms did not alter the level of trauma, suggesting that, in the chinchilla model, for beta(t) > 40 an energy metric may be effective in evaluating the potential of non-G noise environments to produce hearing loss. Reducing the probability of a transient occurring could reduce the permanent effects of the non-G exposures. These results lend support to those standards documents that use an energy metric for gauging the hazard of exposure but only after applying a "correction factor" when high level transients are present. Computing beta on the filtered noise signal [beta(f)] provides a frequency specific metric for the non-G noises that is correlated with the additional frequency specific outer hair cell loss produced by the non-G noise. The data from the abundant and varied exposure conditions show that the kurtosis of the amplitude distribution of a noise environment is an important variable in determining the hazards to hearing posed by non-Gaussian noise environments.

Acoustic Stimulation↗

PubMed2003

[The preparation of an artificial red blood cell substitute by W/O/W double emulsion methods].

A method of preparing methoxypoly (ethylene glycol)-poly-DL-lactide (PELA) microcapsule containing bovine hemoglobin(BHb) by using W/O/W double emulsion-solvent diffusion process for use as artificial red cells was developed. The results suggested that preparation conditions such as solidification method, stirring rate, type of organic solvent had significant influence on the encapsulation efficiency and the activity of bovine hemoglobin. When ethyl acetate was used as the organic solvent and double emulsion-solvent diffusion process was used, there was no significant influence on the activity of hemoglobin if stirring rate was lower than 9000 r/min. High stirring rate, 12,000 r/min, decreased the P(50) and Hill coefficient of the hemoglobin encapsulated. Increasing the volume of solidification solution had an effect of improving the activity of hemoglobin to carry oxygen.

Animals↗

PubMed2002

A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity.

Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 1) catalyzes the final step in the synthesis of active estrogens that stimulate the proliferation of breast cancer cells. Based on the initial premise to make use of the binding energies of both the substrate and cofactor sites, and molecular modeling starting from the enzyme structure, several estradiol-adenosine hybrids were designed and synthesized. Among these hybrids, EM-1745 with a linker of 8-CH2 groups is proved to be the best competitive inhibitor with a Ki of 3.0 +/- 0.8 nM. The crystal structure of the EM-1745 enzyme complex at 1.6 A provides evidence at atomic resolution of strong interactions between both the steroid and cofactor moieties and the enzyme molecule, as illustrated by a deltaA-weighted 2Fo-Fc electron density map contoured at 3.0 delta. The substrate entry loop is further stabilized in this complex compared with previous complexes of the enzyme. These results confirm our initial strategy of combining studies of structural biology and enzyme mechanism in the inhibitor design, which may be applied to other steroidogenic enzymes involved in human diseases.

17-Hydroxysteroid Dehydrogenases↗

PubMed2002

Quantitative study of macroscopic quantum tunneling in a dc SQUID: a system with two degrees of freedom.

To test whether the theory of macroscopic quantum tunneling (MQT) is applicable to systems with 2 degrees of freedom, we experimentally investigated the switching current distribution of a dc SQUID. Using sample parameters determined from measurements at T=4.2 K, we are able to make quantitative comparison to the theories from 8 mK to 4.2 K. The excellent agreement between the data and the MQT theory demonstrates that tunneling from the zero-voltage state of the dc SQUID is well described by the quantum mechanics.

Journal Article↗

PubMed2002

Purification, crystallization and preliminary X-ray diffraction results of human 17beta-hydroxysteroid dehydrogenase type 5.

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the last step in the biosynthesis of all androgens and estrogens, thus playing a pivotal role in sex-hormone metabolism. Human 17beta-HSD type 5 (17beta-HSD5) catalyzes hydride transfer at the 17beta-hydroxy position, but possesses high sequence homology to 3alpha-hydroxysteroid dehydrogenases (3alpha-HSD). Two crystal forms of 17beta-HSD5 in an enzyme-testosterone-NADP ternary complex have been obtained under different crystallization conditions. A form I crystal obtained at pH 8.5 diffracted to 1.32 A. It belonged to space group P2(1), with unit-cell parameters a = 47.41, b = 77.16, c = 48.67 A, beta = 116.32 degrees. Form II crystals obtained at pH 6.5 diffracted to 2.0 A and belonged to space group P6(3), with unit-cell parameters a = b = 110.58, c = 56.89 A.

17-Hydroxysteroid Dehydrogenases↗

PubMed2002

GSH-dependent photolabeling of multidrug resistance protein MRP1 (ABCC1) by [125I]LY475776. Evidence of a major binding site in the COOH-proximal membrane spanning domain.

Substrates transported by the 190-kDa multidrug resistance protein 1 (MRP1) (ABCC1) include endogenous organic anions such as the cysteinyl leukotriene C(4). In addition, MRP1 confers resistance against various anticancer drugs by reducing intracellular accumulation by co-export of drug with reduced GSH. We have examined the properties of LY475776, an intrinsically photoactivable MRP1-specific tricyclic isoxazole modulator that inhibits leukotriene C(4) transport by this protein in a GSH-dependent manner. We show that [125I]LY475776 photolabeling of MRP1 requires GSH but is also supported by several non-reducing GSH derivatives and peptide analogs. Limited proteolysis revealed that [(125)I]LY475776 labeling was confined to the 75-kDa COOH-proximal half of MRP1. More extensive proteolysis generated two major 125I-labeled fragments of approximately 56 and approximately 41 kDa, and immunoblotting with regionally directed antibodies showed that these fragments correspond to amino acids approximately 1045-1531 and approximately 1150-1531, respectively. However, an approximately 33-kDa COOH-terminal immunoreactive fragment was not labeled, inferring that the major [125I]LY475776-labeling site resides approximately between amino acids 1150-1250. This region encompasses transmembrane (TM) segments 16 and 17 at the COOH-proximal end of the third membrane spanning domain of the protein. [125I]LY475776 labeling of mutant MRP1 molecules with substitutions of Trp(1246) in TM17 were reduced >80% compared with wild-type MRP1, confirming that TM17 is important for LY475776 binding. Finally, vanadate-induced trapping of ADP inhibited [125I]LY475776 labeling, suggesting that ATP hydrolysis causes a conformational change in MRP1 that reduces the affinity of the protein for this inhibitor.

Antibodies, Monoclonal↗

PubMed2002

Adaptive filtering of evoked potentials with radial-basis-function neural network prefilter.

Evoked potentials (EPs) are time-varying signals typically buried in relatively large background noise. To extract the EP more effectively from noise, we had previously developed an approach using an adaptive signal enhancer (ASE) (Chen et al., 1995). ASE requires a proper reference input signal for its optimal performance. Ensemble- and moving window-averages were formerly used with good results. In this paper, we present a new method to provide even more effective reference inputs for the ASE. Specifically, a Gaussian radial basis function neural network (RBFNN) was used to preprocess raw EP signals before serving as the reference input. Since the RBFNN has built-in nonlinear activation functions that enable it to closely fit any function mapping, the output of RBFNN can effectively track the signal variations of EP. Results confirmed the superior performance of ASE with RBFNN over the previous method.

Algorithms↗

PubMed2002

Relations among early postexposure noise-induced threshold shifts and permanent threshold shifts in the chinchilla.

Threshold shifts (TS) were measured at various times following a wide variety of noise exposures on over 900 chinchillas. An analysis of postexposure TS measures and noise-induced permanent threshold shift (PTS) showed that, across audiometric test frequency, there was a consistent relation between these variables of the form PTS (dB) = alpha(e(TS/beta) - 1), where, for a given test frequency, alpha (dB) and beta (dB) are constants. TSs were measured immediately following exposure (TS0), 24 h after exposure (TS24), and at several intermediate times in order to estimate the maximum TS (TSmax). Correlation between TS and PTS at the various test frequencies was highest for TS24. An analysis of the 90th-percentile PTS showed a linear growth of PTS with TS24 of approximately 0.7 dB PTS/dB TS24. These data provide some support, in the chinchilla model, for a variation of the three postulates originally presented by Kryter et al. [J. Acoust. Soc. Am. 39, 451 (1966)]. Specifically: (i) TS24 is a consistent measure of the effects of a traumatic noise exposure. (ii) All exposures that produce a given TS24 will be equally hazardous. (iii) Noise-induced PTS in the most susceptible animals, following many years of exposure, is approximately equal to (0.7)TS24 measured after an 8-h exposure to the same noise.

Animals↗

PubMedDate not supplied

Scientific perspectives on drug transporters and their role in drug interactions.

Recently, increased interest in drug transporters and research in this area has revealed that drug transporters play an important role in modulating drug absorption, distribution, and elimination. Acting alone or in concert with drug metabolizing enzymes they can affect the pharmacokinetics and pharmacodynamics of a drug. This commentary will focus on the potential role that drug transporters may play in drug-drug interactions and what information may be needed during drug development and new drug application (NDA) submissions to address potential drug interactions mediated by transporters.

Drug Interactions↗