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Biomedical subjects

Chun Yang

Publications and source records attributed to Chun Yang.

84 records · Page 5Linked to original sources
PubMed2002

Carrier mediated uptake of L-tyrosine and its competitive inhibition by model tyrosine linked compounds in a rabbit corneal cell line (SIRC)--strategy for the design of transporter/receptor targeted prodrugs.

The objective of this study was to investigate the presence of amino acid transporters on the corneal epithelium and to enhance corneal drug absorption through prodrug modification targeted to the amino acid transporters. SIRC was used as a model cell line representing the corneal epithelium. Uptake studies were carried out using [3H] L-tyrosine at 37 degrees C. Temperature, energy and pH dependence studies were carried out. The uptake seems to be composed of a major saturable and minor non-saturable component (V(max) =2.9+/-0.62 nmoles/min/mg protein, K(m) =71+/-21 microM, K(d) =2.6+/-0.6 nl/min/mg protein). No significant inhibition of uptake was observed in the presence of metabolic inhibitors or in the absence of sodium. Competitive inhibition studies were performed in the presence of various amino acids and model tyrosine conjugates (p-nitro and p-chloro benzyl ether conjugate of L-tyrosine). Uptake was inhibited by neutral aromatic and large neutral aliphatic amino acids. L-Tyrosine uptake was inhibited by its ether conjugates in a concentration dependent manner suggesting that these compounds may be sharing the same transport mechanism. This study provides biochemical evidence of the presence of a large neutral amino acid transport system on the corneal epithelium, which may be utilized to enhance the corneal drug transport.

Amino Acid Transport Systems↗
PubMed2002

Electroosmotic flow in a capillary annulus with high zeta potentials.

The electroosmotic flow through an annulus is analyzed under the situation when the two cylindrical walls carry high zeta potentials. The analytical solutions for the electric potential profile and the electroosmotic flow field in the annulus are obtained by solving the Poisson-Boltzmann equation and the Stokes equation under an analytical scheme for the hyperbolic sine function. A mathematical expression for the average electroosmotic velocity is derived in a fashion similar to the Smoluchowski equation. Hence, a correction formula is introduced to modify the Smoluchowski equation, taking into account contributions due to the finite thickness of the electric double layer (EDL) and the geometry ratio-dependent correction. Specifically, under a circumstance when the two annular walls are oppositely charged, the flow direction can be determined from the sign of such correction formula, and there exists a zero-velocity plane inside the annulus. With the assumption of large electrokinetic diameters, the location of the zero-velocity plane can be estimated from the analytical expression for the velocity distribution. In addition, the characteristics of the electroosmotic flow through the annulus are discussed under the influences of the EDL parameters and geometric ratio of the inner radius to the outer radius of the annulus.

Journal Article↗
PubMed2002

Regulation of aromatase promoter activity in human breast tissue by nuclear receptors.

Using the yeast one-hybrid approach to screen a human breast tissue hybrid cDNA expression library, we have found that four orphan/nuclear receptors, ERRalpha-1, EAR-2, COUP-TFI (EAR-3), and RARgamma, bind to the silencer (S1) region of the human aromatase gene. S1 down regulates promoters I.3 and II of the human aromatase gene. In this study, the interaction of EAR-2, COUP-TFI, and RARgamma with S1 was confirmed by DNA mobility shift analysis. In contrast to the findings that ERRalpha-1 behaves as a positive regulatory factor, these three nuclear receptors were found, by mammalian cell transfection experiments, to act as negative regulatory factors by binding to S1. Furthermore, the negative action of these three nuclear receptors could override the positive effect of ERRalpha-1. RT-PCR analysis of 11 cell lines and 55 human breast tumor specimens has shown that these nuclear receptors are expressed in human breast tissue. Since EAR-2, COUP-TFI, and RARgamma are expressed at high levels, it is likely that S1 is a negative regulatory element that suppresses aromatase promoters I.3 and II in normal breast tissue. In cancer tissue, S1 may function as a positive element since ERRalpha-1 is expressed, but EAR-2 and RARgamma are only present in a small number of tumor specimens. This hypothesis is sustained by the finding that there is a weak inverse correlation between the expression of COUP-TFI and that of aromatase in breast tumor tissue. Our studies have revealed that estrogen receptor alpha (ERalpha) can also bind to S1, in a ligand-dependent manner. By binding to S1, ERalpha down-regulates the aromatase promoter activity. These results demonstrate that nuclear receptors play important roles in modulating aromatase expression in human breast tissue.

Aromatase↗
PubMed2002

Transient analysis of electroosmotic flow in a slit microchannel.

The transient aspects of electroosmotic flow in a slit microchannel are studied. Exact solutions for the electrical potential profile and the transient electroosmotic flow field are obtained by solving the complete Poisson-Boltzmann equation and the Navier-Stokes equation under an analytical approximation for the hyperbolic sine function. The characteristics of the transient electroosmotic flow are discussed under influences of the electric double layer and the geometric size of the microchannel.

Journal Article↗
PubMed2002

Extraction of pharmaceutical components from Ginkgo biloba leaves using supercritical carbon dioxide.

Ginkgo biloba extract (GBE) has many remarkable pharmacological and clinical effects, and it is the most frequently used product as a phytomedicine in many countries. The combination of primary extraction with 70% ethanol followed by extraction using supercritical carbon dioxide provides an efficient and economical means for obtaining flavonoids and terpenoids from Ginkgo biloba leaves. The supercritical fluid extraction (SFE) is affected by pressure, temperature, and the concentration of modifier in the extractant. At the most favorable experimental conditions of 300 MPa, 60 degrees C, and carbon dioxide containing 5% ethanol as modifier, the yield of GBE powder is 2.1% (based on the air-dry weight of Ginkgo biloba leaves) compared to a yield of only 1.8% by conventional solvent extraction. The contents of flavonoids and terpenoids in SFE products are 35.9% and 7.3%, respectively, which are significantly higher than the general standards of 24% and 6%, respectively.

Carbon Dioxide↗
PubMed2002

Transcriptional regulation of aromatase expression in human breast tissue.

Aromatase (CYP19) is the estrogen synthetase that converts androgen to estrogen. The expression of aromatase in breast cancer cells and surrounding stromal cells is up regulated compared to non-cancerous cells. In situ estrogen synthesis is thought to stimulate breast cancer growth in both an autocrine and a paracrine manner. A complex mechanism is involved in the control of human aromatase expression, in that seven promoters have been identified and found to be utilized in a tissue-selective manner. Increased aromatase expression in breast tumors is, in part, attributed to changes in the transcriptional control of aromatase expression. While promoter I.4 is the main promoter that controls aromatase expression in non-cancer breast tissue, promoters II and I.3 are the dominant promoters that drive aromatase expression in breast cancer tissue. During the last several years, our laboratory performed a series of studies to examine the transcription regulatory mechanism of aromatase expression in breast cancer cells. We functionally characterized promoters II and I.3, and carried out DNase 1 footprinting analysis that identified two regulatory elements, S1 and CREaro. Using the yeast one-hybrid approach to screen a human breast tissue hybrid cDNA expression library, we found that four orphan/nuclear receptors, ERR alpha-1, EAR-2, COUP-TFI and RAR gamma, bind to the S1 element, and that CREB1, Snail (SnaH) and Slug proteins bind to the CREaro element. Studies from this and other laboratories have revealed that in cancer tissue versus normal tissue, several positive regulatory proteins (e.g. ERR alpha-1 and CREB1) are present at higher levels and several negative regulatory proteins (e.g. EAR-2, COUP-TFI, RAR gamma, Snail and Slug proteins) are present at lower levels. This may explain why the activity of promoters II and I.3 is up regulated in cancer tissue. An understanding of the molecular mechanisms of aromatase expression between non-cancerous and cancerous breast tissue, at the transcriptional level, may help in the design of a therapy based on the suppression of aromatase expression in breast cancer tissue.

Animals↗
PubMed2002

Prevention and treatment of breast cancer by suppressing aromatase activity and expression.

Estrogen promotes the proliferation of breast cancer cells. Aromatase is the enzyme that converts androgen to estrogen. In tumors, expression of aromatase is upregulated compared to that of surrounding noncancerous tissue. Tumor aromatase is thought to stimulate breast cancer growth in both an autocrine and a paracrine manner. A treatment strategy for breast cancer is to abolish in situ estrogen formation with aromatase inhibitors. In addition, aromatase suppression in postmenapausal women is being evaluated as a potential chemopreventive modality against breast cancer. One area of aromatase research in this laboratory is the identification of foods and dietary compounds that can suppress aromatase activity. In vitro and in vivo studies have found that grapes and mushrooms contain chemicals that can inhibit aromatase. Therefore, a diet that includes grapes and mushrooms would be considered preventative against breast cancer. Another area of our aromatase research is the elucidation of the regulatory mechanism of aromatase expression in breast cancer tissue. Increased aromatase expression in breast tumors is attributed to changes in the transcriptional control of aromatase expression. Whereas promoter I.4 is the main promoter that controls aromatase expression in noncancerous breast tissue, promoters II and I.3 are the dominant promoters that drive aromatase expression in breast cancer tissue. Our recent gene regulation studies revealed that in cancerous versus normal tissue, several positive regulatory proteins (e.g., nuclear receptors and CREB1) are present at higher levels and several negative regulatory proteins (e.g., snail and slug proteins) are present at lower levels. This may explain why the activity of promoters II and I.3 is upregulated in cancerous tissue. In addition, our in vitro transcription/translation analysis using plasmids containing T7 promoter and the human snail gene as a reporter capped with different untranslated exon Is revealed that exon PII-containing transcripts were translated more effectively than were exon I.3-containing transcripts. An understanding of the molecular mechanisms of aromatase expression between noncancerous and cancerous breast tissue, at both transcriptional and translational levels, may help in the design of a therapy based on suppressing aromatase expression in breast cancer tissue.

Aromatase↗
PubMed2002

Removal of organic contaminants from water or wastewater with liquefied gases.

This study utilized liquefied gases (LG) as extractant to remove various organic contaminants including halogenated hydrocarbons and phenols as well as aromatic compounds from aqueous matrices. Orthogonal experiments were performed to optimize the operating conditions such as temperature, co-solvents and so on. Under favorable conditions, high removal efficiencies can be readily achieved for a great number of representative model organic contaminants, the removal efficiencies for most of the hydrophobic contaminants were greater than 90% in a single extraction stage. Tentative effort was also done for the removal of extracted contaminants from recycled liquefied gases.

Butanes↗
PubMed2002

[TCR-mediated signaling].

In recent years, major progress has been obtained in studying the early events in TCR-mediated signaling. c-Cb1 has been found to be a negative regulatory factor of the tyrosine kinases in ZAP-70/SyK family. The studies on LAT, SLP-76, ItK and Vav have shown their roles in the signal transduction of Ras and phospholipase Cx1 to Ca2+. Micro-glycolipid raft also plays important role in T cell activation. This minireview shows a brief introduction to the process of TCR-mediated signaling.

Animals↗
PubMedDate not supplied

Outcome prediction for critically ill cirrhotic patients: a comparison of APACHE II and Child-Pugh scoring systems.

Cirrhotic patients admitted to the medical intensive care unit (ICU) are associated with high mortality rates. The prognosis of critically ill cirrhotic patients is determined by the extent of hepatic and extrahepatic organ dysfunction. This study was conducted to assess and compare the accuracy of the Child-Pugh classification and APACHE II scores, obtained on the first day of ICU admission, in predicting hospital mortality in critically ill cirrhotic patients. One hundred thirty-five patients diagnosed with liver cirrhosis were admitted to the medical ICU between January 2002 and March 2003. Information considered necessary to compute the Child-Pugh and APACHE II scores on the first day of ICU admission was prospectively collected. The overall hospital mortality rate was 66.6%. Liver disease was most commonly attributed to hepatitis B viral infection. The APACHE II scores demonstrate a good fit using the Hosmer and Lemeshow goodness-of-fit test. Furthermore, by using the areas under receiver operating characteristic (AUROC) curve, the APACHE II scores demonstrated a better discriminative power (AUROC 0.833 +/- 0.039) than Child-Pugh scores (AUROC 0.75 +/- 0.05) (P=.024). This investigation confirms the grave prognosis for the cirrhotic patients admitted to the ICU. While both Child-Pugh and the APACHE II scores can satisfactorily predict the outcomes for critically ill cirrhotic patients, APACHE II is more powerful in discriminating the survivors from the nonsurvivors.

APACHE↗