Biomedical subjects

Yuping Chen

Publications and source records attributed to Yuping Chen.

10 recordsLinked to original sources

PubMed2005

Broadening of the second-harmonic phase-matching bandwidth in type II periodically poled KTP.

We have theoretically demonstrated type II broadband second-harmonic generation (SHG) based on a quasi-phase-matching (QPM) configuration in periodically poled KTP (PPKTP). The wavelength dependence of QPM grating periods at different temperatures of 5 degrees C, 25 degrees C, and 45 degrees C is calculated with the crystal length of 1 cm. We find a very wide bandwidth, as large as 42.6 nm, of fundamental wavelength of 1.58 microm at the telecommunication band with the QPM period of 48.9 microm at 25 degrees C. The corresponding bandwidths of incident angle and temperature are found to be 4.24 degrees and 14.8 degrees C, respectively. The comparison among PPKTP, periodically poled lithium niobate (PPLN), and MgO:PPLN reveals the unique performance of PPKTP in the broadband SHG.

Journal Article↗

PubMed2005

Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha.

Cytochrome P450 (P450) enzymes play important roles in the metabolism of endogenous and xenobiotic substrates in humans. CYP2C8 is an important member of the CYP2C subfamily, which metabolizes both endogenous compounds (i.e., arachidonic acids and retinoic acid) and xenobiotics (e.g., paclitaxel). Induction of P450 enzymes by drugs can result in tolerance as well as drug-drug interactions. CYP2C8 is the most strongly inducible member of the CYP2C subfamily in human hepatocytes, but the mechanism of induction by xenobiotics has not been delineated. To determine the mechanisms controlling the regulation of this important P450, we cloned the 5'-flanking region of CYP2C8 and investigated its transcriptional regulation by nuclear factors such as the pregnane X receptor (PXR), constitutive androstane receptor (CAR), glucocorticoid receptor (GR), and hepatic nuclear factor 4 (HNF4alpha) that are known to be involved in the induction of other P450 enzymes using both cell lines and primary hepatocyte models. We initially identified a distal PXR/CAR-binding site in the CYP2C8 promoter that confers inducibility of CYP2C8 via the PXR agonist/ligand rifampicin and the CAR agonist/ligand CITCO [6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime]. A glucocorticoid-responsive element was identified that mediates dexamethasone induction via the GR. We finally identified an HNF4alpha-binding site within the CYP2C8 basal promoter region that is cis-activated by cotransfected HNF4alpha. In summary, the present studies show that CAR, PXR, GR, and HNF4alpha can regulate CYP2C8 expression and identify specific cis-elements within the promoter that control these regulatory pathways.

Androstanes↗

PubMed2005

The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4alpha to synergistically activate the human CYP2C9 promoter.

CYP2C9 is an important human drug-metabolizing enzyme that is expressed primarily in liver. Recent studies in our laboratory have shown that the nuclear receptor pregnane X receptor (PXR) is important in the transcriptional activation of the CYP2C9 promoter by drugs such as rifampicin and that the essential element is a constitutive androstane receptor (CAR)/PXR site -1839 bp upstream of the translation start site. Both CAR and PXR transcriptionally up-regulate the CYP2C9 promoter via these elements. In the present study, we ask whether additional sites in the proximal promoter also play a role in this induction. We identify two proximal hepatic nuclear factor (HNF) 4alpha binding sites at -152 and -185 bp of the CYP2C9 promoter, both of which bind HNF4alpha in gel shift assays and transcriptionally up-regulate this promoter in response to HNF4alpha in HepG2 cells. HNF4alpha synergizes with CAR and with PXR in HepG2 cells treated with rifampicin. The synergy only occurs when the CAR/PXR binding site at -1839 bp is present. Mutation of the two HNF4alpha binding sites differentially prevented up-regulation of CYP2C9 promoter by both CAR as well as HNF4alpha, synergy between the two receptors, and essentially abolished induction by rifampicin in HepG2 cells transfected with PXR. These studies strongly support the hypothesis that there is cross talk between distal CAR/PXR sites and HNF4alpha binding sites in the CYP2C9 promoter and that the HNF4alpha sites are required for maximal induction of the CYP2C9 promoter.

Aryl Hydrocarbon Hydroxylases↗

PubMed2005

Direct quasi-phase-matched fourth-harmonic generation.

We have theoretically demonstrated direct fourth-harmonic generation (FHG) based on a quasi-phase-matching (QPM) configuration in periodically poled lithium niobate. The wavelength dependence of period of FHG QPM gratings is calculated. Bandwidths of fundamental wavelength, temperature, and incident angle are also studied. We find a very wide bandwidth, as large as 115 nm, of fundamental wavelength near the wavelength of 3797 nm with the QPM period of 9.73 microm. The numerical calculation shows that the conversion efficiency for QPM FHG and cascading QPM by two-step second-harmonic generation is almost identical.

Journal Article↗

PubMed2005

Index profiling of anisotropic graded-index planar waveguides from effective indices.

We present a method for recovering the refractive-index profile of an anisotropic graded-index waveguide from the effective indices by using a cubic spline interpolation function. The first and second derivatives of cubic splines are continuous to ensure a smooth index profile, which is consistent with practical graded-index distributions. A straightforward iteration with an exact dispersion equation to verify the interpolated profile makes this method easy and reliable for application. This approach is proved by numerical analysis of several typical index distributions and experimental examples showing that the refractive-index profiles in anisotropy can be reconstructed close to the exact profile. Waveguides with both more modes (more than four guiding modes) and fewer modes (two to four) can be universally profiled with good accuracy.

Journal Article↗

PubMed2004

Similar and functionally typical kinematic reaching parameters in 7- and 15-month-old in utero cocaine-exposed and unexposed infants.

This study examined the effects of intrauterine cocaine exposure on the reaches of 19 exposed and 15 unexposed infants at 7 and 15 months using kinematic measures. Infants sat at a table and reached for a rattle, a toy doll, and a chair. Videotaped reaches were digitized using the Peak Performance system. Kinematic movement variables were extracted (e.g., reach duration, peak velocity, movement units, path length) and ratios computed (e.g., path length divided by number of movement units). Regardless of exposure status, reaches of older infants were faster, more direct, had fewer movement units, and covered more distance with the first movement unit. Exposed infants covered more distance per movement unit than unexposed infants, but there were no other significant differences. Reaches of exposed and unexposed infants were essentially similar. Importantly, reach parameters for these high-risk infants were similar to reach parameters for infants at lower social and biological risk.

Adult↗

PubMed2004

Explicit analysis of anisotropic planar waveguides by the analytical transfer-matrix method.

The propagation properties of light in anisotropic optical planar waveguides with different index distributions are investigated with the analytical transfer-matrix method. Dispersion equations are analytically deduced by the method in terms of different index profiles. It is shown by examples that this method exhibits good accuracy compared with numerical methods while still holding physical insight.

Journal Article↗

PubMed2003

Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor.

Human CYP2C9 is important in the metabolism of numerous clinically used drugs such as the anticoagulant warfarin, the anticonvulsant phenytoin, antidiabetic drugs such as tolbutamide and glipizide, the hypertensive agent losartan, and numerous nonsteroidal anti-inflammatory drugs. Several studies have reported that certain drugs such as rifampicin and phenobarbital induce CYP2C9, but the molecular basis for this induction remains unknown. In the present study, we demonstrate that the human pregnane X receptor (hPXR) mediates induction of CYP2C9 by the prototype drugs rifampicin, hyperforin (found in St. John's Wart), and phenobarbital. Deletion and mutagenesis studies with luciferase reporter constructs showed that a functional PXR-responsive element located -1839/-1824 base pairs upstream from the translation start site was the primary binding site mediating the rifampicin induction of CYP2C9. This site was previously described as a constitutive androstane receptor-responsive element (CAR-RE). Mutational analysis of 3- and 12-kilobase CYP2C9 promoter fragments indicated that this proximal binding site was essential for rifampicin inducibility, although a cooperative effect could be attributed to a second CAR-RE located at -2899/-2883. In summary, we have demonstrated rifampicin induction of CYP2C9 promoter constructs that is consistent with the magnitude of induction of CYP2C9 protein and mRNA reported in vivo and in primary human hepatocytes, and we have identified the cis-element essential for this response. This is the first report to demonstrate that the nuclear receptor PXR mediates induction of CYP2C9 with rifampicin, phenobarbital, and hyperforin.

Anti-Bacterial Agents↗

PubMed2003

Electro-optic Solc-type wavelength filter in periodically poled lithium niobate.

We demonstrate an electro-optic Solc-type wavelength filter in periodically poled lithium niobate (PPLN). A Solc-type transmission spectrum is observed experimentally in PPLN with four periods from 20.2 to 20.8 microm. Modulation of the transmission power of the filter is realized by application of electric fields along the Y axis of the PPLN. It is observed that the wavelength can also be tuned by temperature.

Journal Article↗

PubMed2003

Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter.

CYP2C19 is an important human drug-metabolizing enzyme that metabolizes a number of clinically used drugs including the antiulcer drug omeprazole, the anxiolytic drug diazepam, the beta-blocker propranolol, the antimalarial drug proguanil, certain antidepressants and barbiturates, and the prototype substrate S-mephenytoin. Previous studies show that compounds such as rifampicin and dexamethasone induce CYP2C19 both in vivo in humans and in vitro in human hepatocytes. This study examines the transcriptional regulation of CYP2C19. Analysis of the CYP2C19 promoter revealed a single constitutive androstane receptor (CAR) binding site (CAR-RE; -1891/-1876 bp) and a glucocorticoid-responsive element (GRE; -1750/-1736 bp). Gel-shift assays showed that CAR-RE binds CAR and pregnane X receptor (PXR). Cotransfection with hCAR, mCAR, or hPXR in HepG2 cells up-regulated transcription of CYP2C19 promoter constructs, whereas mutation of the -1891-bp CAR-RE abolished up-regulation. Expression with hCAR also up-regulated endogenous CYP2C19 mRNA content in HepG2 cells. Androstenol repressed the mCAR-mediated constitutive activation of the CYP2C19 promoter in HepG2 cells, whereas the potent mCAR ligand 1,4-bis[2-3,5-dichloropyridyloxyl)] benzene derepressed this response. Rifampicin produced a modest increase in promoter activity in cells cotransfected with hPXR. Dexamethasone activated the -2.7-kb CYP2C19 promoter constructs in HepG2 cells only in the presence of cotransfected glucocorticoid receptor (GR), whereas the GR antagonist mifepristone inhibits this response. Mutation of the GRE abolishes dexamethasone activation. This is the first study to identify nuclear receptor binding sites (CAR/PXR and GR) in the CYP2C19 promoter and to suggest that these receptors may up-regulate CYP2C19 constitutively and possibly its response to drugs.

Aryl Hydrocarbon Hydroxylases↗