Biomedical subjects

Yi Zhao

Publications and source records attributed to Yi Zhao.

At least 73 records · Page 4Linked to original sources

PubMed2004

Analysis of MDR1 haplotypes in Parkinson's disease in a white population.

The MDR1 multidrug transporter is important in regulating environmental xenobiotics and hence may play a causative role in Parkinson's disease (PD). MDR1 haplotype comprising 2677 G > T/A and 3435 C > T may be protective against PD. Using a case control methodology, we investigated the association of MDR1 haplotypes (single nucleotide polymorphisms (SNPs) 2677 G > T/A and 3435 C > T) in a Polish PD population. Seven SNPs, extending from the promoter to exon 28 of the MDR1 gene in 158 PD patients and 139 healthy controls were evaluated. Specifically we examined the association of haplotypes containing SNPs 2677 G > T/A and 3435 C > T and risk of PD. The multivariate logistic regression model was used to evaluate the effects of the covariates on the phenotypes. Haplotypes' frequencies were estimated using the Expectation-Maximization algorithm. The frequency of each individual SNPs; -41 A > G (intron -1), -145 C > G (exon 1), -129 T > C (exon 1), 1236 T > C (exon 12), 2677 G > T/A (exon 21), 3435 C > T (exon 26), and 4036 A > G (exon 28) did not differ between PD and controls. However, there was a trend towards significance in PD patients having the haplotype 2677G-3435C (p < 0.09, chi-square 2.85, odds ratio 0.25, 95% CI 0.06-1.08). Haplotype constructs of the other loci did not differ significantly between the two groups. There was a weak protective effect of the haplotype 2677G-3435C in our white population. However, the MDR1 haplotypes did not generally modulate the risk of PD.

Adult↗

PubMed2004

Evaluation of canonical and microcanonical nonadiabatic reaction rate constants by using the Zhu-Nakamura formulas.

We consider a problem of calculating both thermal and microcanonical rate constants for nonadiabatic chemical reactions. Instead of using the conventional transition state theory, we use a generalized seam surface and introduce a concept of a coordinate dependent effective nonadiabatic transition probability based on the Zhu-Nakamura theory which can treat the nonadiabatic tunneling properly. The present approach can be combined with Monte Carlo method so as to be applicable to chemical reactions in complicated systems. The method is demonstrated to work well in wide energy and temperature range. Numerical tests also show that it is very essential for accurate evaluation of the thermal rate constant to use the generalized seam surface and take into account the nonadiabatic tunneling effect.

Journal Article↗

PubMed2004

The interactome as a tree--an attempt to visualize the protein-protein interaction network in yeast.

The refinement and high-throughput of protein interaction detection methods offer us a protein-protein interaction network in yeast. The challenge coming along with the network is to find better ways to make it accessible for biological investigation. Visualization would be helpful for extraction of meaningful biological information from the network. However, traditional ways of visualizing the network are unsuitable because of the large number of proteins. Here, we provide a simple but information-rich approach for visualization which integrates topological and biological information. In our method, the topological information such as quasi-cliques or spoke-like modules of the network is extracted into a clustering tree, where biological information spanning from protein functional annotation to expression profile correlations can be annotated onto the representation of it. We have developed a software named PINC based on our approach. Compared with previous clustering methods, our clustering method ADJW performs well both in retaining a meaningful image of the protein interaction network as well as in enriching the image with biological information, therefore is more suitable in visualization of the network.

Algorithms↗

PubMed2004

Genetic analysis of DJ-1 in a cohort Parkinson's disease patients of different ethnicity.

Mutations in the DJ-1 gene have been described in autosomal recessive Parkinson's disease patients (ARPD) of European ancestry and young onset (YOPD) Ashkenazi Jewish and Afro-Caribbean patients. There is little information on the prevalence of DJ-1 mutations amongst Asian PD populations. In this study, we examined for DJ-1 mutations in consecutive YOPD and ARPD in a multi-ethnic cohort (Chinese, Malays, and Indians) of PD patients in a tertiary referral center. Sequence analysis of all the exons and the exon and intron boundaries of the DJ-1 gene were carried out. We did not find any DJ-1 mutations in these patients. A number of intronic variants with genotype frequency ranging from 15 to 90% were detected. Unlike Parkin, pathogenic DJ-1 mutations appear to be restricted to certain populations and are unlikely to be of clinical importance in our Asian cohort.

Adult↗

PubMed2004

Ubiquitylation of nascent globin chains in a cell-free system.

The ubiquitin/proteasome pathway for degradation of completed and nascent globin chains was evaluated using a cell-free in vitro coupled transcription/translation assay. No decrease in radiolabeled globin chains was observed when ubiquitin, energy regenerating source (or ATP), and E1 and E2 enzymes were added 30 min after the start of translation when globin chain synthesis had plateaued. In contrast, the addition of these components prior to the start of translation resulted in no radiolabeled globin chains after 30 min. The loss of radiolabeled globin chains was dependent on ATP concentration; the higher the concentration, the less the radiolabeled globin chains formed. Prior to the initiation of transcription/translation, cell extract was preincubated with the proteasomal inhibitor MG132 in the absence of globin chain expression vector after which ubiquitin-protein isopeptidase inhibitor, Ubal, and expression vector were added in the presence of 1.5 mm ATP. Thereafter, radiolabeled monoubiquitylated and multiubiquitylated globin chains with few unmodified globin chains were formed. Our results suggest that polyubiquitylated globin chains are localized to the polysomal fractions. These results suggest that nascent globin chains are potential targets for ubiquitylation and deubiquitylation during or soon after translation and that ATP levels play a role in the balance between polypeptide synthesis and degradation.

Adenosine Triphosphate↗

PubMed2004

Casein kinase 1alpha interacts with retinoid X receptor and interferes with agonist-induced apoptosis.

Agonists of retinoid X receptors (RXRs), which include the natural 9-cis-retinoic acid and synthetic analogs, are potent inducers of growth arrest and apoptosis in some cancer cells. As such, they are being used in clinical trials for the treatment and prevention of solid tumors and are used to treat cutaneous T cell lymphoma. However, the molecular mechanisms that underlie the anti-cancer effects of RXR agonists remain unclear. Here, we show that a novel pro-apoptotic pathway that is induced by RXR agonist is negatively regulated by casein kinase 1alpha (CK1alpha). CK1alpha associates with RXR in an agonist-dependent manner and phosphorylates RXR. The ability of an RXR agonist to recruit CK1alpha to a complex with RXR in cells correlates inversely with its ability to inhibit growth. Remarkably, depletion of CK1alpha in resistant cells renders them susceptible to RXR agonist-induced growth inhibition and apoptosis. Our study shows that CK1alpha can promote cell survival by interfering with RXR agonist-induced apoptosis. Inhibition of CK1alpha may enhance the anti-cancer effects of RXR agonists.

Animals↗

PubMed2004

A retinoid-related molecule that does not bind to classical retinoid receptors potently induces apoptosis in human prostate cancer cells through rapid caspase activation.

Synthetic retinoid-related molecules, such as N-(4-hydroxyphenyl)retinamide (fenretinide) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induce apoptosis in a variety of malignant cells. The mechanism(s) of action of these compounds does not appear to involve retinoic acid receptors (RARs) and retinoid X receptors (RXRs), although some investigators disagree with this view. To clarify whether some retinoid-related molecules can induce apoptosis without involving RARs and/or RXRs, we used 4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-E-propenyl] benzoic acid (AGN193198) that neither binds effectively to RARs and RXRs nor transactivates in RAR- and RXR-mediated reporter assays. AGN193198 potently induced apoptosis in prostate, breast, and gastrointestinal carcinoma cells and in leukemia cells. AGN193198 also abolished growth (by 50% at 130-332 nM) and induced apoptosis in primary cultures established from prostatic carcinoma (13 patients) and gastrointestinal carcinoma (1 patient). Apoptosis was induced rapidly, as indicated by mitochondrial depolarization and DNA fragmentation. Molecular events provoked by AGN193198 included activation of caspase-3, -8, -9, and -10 (by 4-6 h) and the production of BID/p15 (by 6 h). These findings show that caspase-mediated induction of apoptosis by AGN193198 is RAR/RXR-independent and suggest that this compound may be useful in the treatment of prostate cancer.

Antineoplastic Agents↗

PubMed2004

Path integral calculation of thermal rate constants within the quantum instanton approximation: application to the H + CH4 --> H2 + CH3 hydrogen abstraction reaction in full Cartesian space.

The quantum instanton approximation for thermal rate constants of chemical reactions [Miller, Zhao, Ceotto, and Yang, J. Chem. Phys. 119, 1329 (2003)], which is modeled after the earlier semiclassical instanton approach, is applied to the hydrogen abstraction reaction from methane by a hydrogen atom, H + CH4 --> H2 + CH3, using a modified and recalibrated version of the Jordan-Gilbert potential surface. The quantum instanton rate is evaluated using path integral Monte Carlo approaches based on the recently proposed implementation schemes [Yamamoto and Miller, J. Chem. Phys. 120, 3086 (2004)]. The calculations were carried out using the Cartesian coordinates of all the atoms (thus involving 18 degrees of freedom), thereby taking explicit account of rotational effects of the whole system and also allowing the equivalent treatment of the four methane hydrogens. To achieve such a treatment, we present extended forms of the path integral estimators for relevant quantities that may be used for general N-atom systems with any generalized reaction coordinates. The quantum instanton rates thus obtained for the temperature range T = 200-2000 K show good agreement with available experimental data, which gives support to the accuracy of the underlying potential surface used.

Journal Article↗

PubMed2004

Date of origin of the SARS coronavirus strains.

BACKGROUND: A new respiratory infectious epidemic, severe acute respiratory syndrome (SARS), broke out and spread throughout the world. By now the putative pathogen of SARS has been identified as a new coronavirus, a single positive-strand RNA virus. RNA viruses commonly have a high rate of genetic mutation. It is therefore important to know the mutation rate of the SARS coronavirus as it spreads through the population. Moreover, finding a date for the last common ancestor of SARS coronavirus strains would be useful for understanding the circumstances surrounding the emergence of the SARS pandemic and the rate at which SARS coronavirus diverge. METHODS: We propose a mathematical model to estimate the evolution rate of the SARS coronavirus genome and the time of the last common ancestor of the sequenced SARS strains. Under some common assumptions and justifiable simplifications, a few simple equations incorporating the evolution rate (K) and time of the last common ancestor of the strains (T0) can be deduced. We then implemented the least square method to estimate K and T0 from the dataset of sequences and corresponding times. Monte Carlo stimulation was employed to discuss the results. RESULTS: Based on 6 strains with accurate dates of host death, we estimated the time of the last common ancestor to be about August or September 2002, and the evolution rate to be about 0.16 base/day, that is, the SARS coronavirus would on average change a base every seven days. We validated our method by dividing the strains into two groups, which coincided with the results from comparative genomics. CONCLUSION: The applied method is simple to implement and avoid the difficulty and subjectivity of choosing the root of phylogenetic tree. Based on 6 strains with accurate date of host death, we estimated a time of the last common ancestor, which is coincident with epidemic investigations, and an evolution rate in the same range as that reported for the HIV-1 virus.

China↗

PubMed2004

The arsenic clusters Asn (n = 1-5) and their anions: structures, thermochemistry, and electron affinities.

The molecular structures, electron affinities, and dissociation energies of the As(n)/As(-) (n) (n = 1-5) species have been examined using six density functional theory (DFT) methods. The basis set used in this work is of double-zeta plus polarization quality with additional diffuse s- and p-type functions, denoted DZP++. These methods have been carefully calibrated (Chem Rev 2002, 102, 231) for the prediction of electron affinities. The geometries are fully optimized with each DFT method independently. Three different types of the neutral-anion energy separations reported in this work are the adiabatic electron affinity (EA(ad)), the vertical electron affinity (EA(vert)), and the vertical detachment energy (VDE). The first dissociation energies D(e)(As(n-1)-As) for the neutral As(n) species, as well as those D(e)(As(-) (n-1)-As) and D(e) (As(n-1)-As(-)) for the anionic As(-) (n) species, have also been reported. The most reliable adiabatic electron affinities, obtained at the DZP++ BLYP level of theory, are 0.90 (As), 0.74 (As(2)), 1.30 (As(3)), 0.49 (As(4)), and 3.03 eV (As(5)), respectively. These EA(ad) values for As, As(2), and As(4) are in good agreement with experiment (average absolute error 0.09 eV), but that for As(3) is a bit smaller than the experimental value (1.45 +/- 0.03 eV). The first dissociation energies for the neutral arsenic clusters predicted by the B3LYP method are 3.93 eV (As(2)), 2.04 eV (As(3)), 3.88 eV (As(4)), and 1.49 eV (As(5)). Compared with the available experimental dissociation energies for the neutral clusters, the theoretical predictions are excellent. Two dissociation limits are possible for the arsenic cluster anions. The atomic arsenic results are 3.91 eV (As(-) (2) --> As(-) + As), 2.46 eV (As(-) (3) --> As(-) (2) + As), 3.14 eV (As(-) (4) --> As(-) (3) + As), and 4.01 eV (As(-) (5) --> As(-) (4) + As). For dissociation to neutral arsenic clusters, the predicted dissociation energies are 2.43 eV (As(-) (3) --> As(2) + As(-)), 3.53 eV (As(-) (4) --> As(3) + As(-)), and 3.67 eV (As(-) (5) --> As(4) + As(-)). For the vibrational frequencies of the As(n) series, the BP86 and B3LYP methods produce good results compared with the limited experiments, so the other predictions with these methods should be reliable.

Journal Article↗

PubMed2004

Nurr1 mutational screen in Parkinson's disease.

We performed sequence analysis of all the exons and exon-intron boundaries in familial and young-onset Parkinson's disease (PD) in an Asian cohort. None of the patients carried any pathogenic mutations in the Nurr1 gene. We demonstrated a 5 to 10% prevalence of the intron 7 +33 C-->T variant among Malay and Indian PD and healthy controls, suggesting that this variant, which was previously described only in 1 Chinese patient, was not a silent mutation but a common polymorphic variant in some ethnic races.

Adult↗

PubMed2004

Use of elderly donors (> 60 years) for liver transplantation.

BACKGROUND: As the demand for liver transplantation has become greater than the availability of donor livers, the criteria for donor selection or rejection are more important than ever before. In view of an increasing number of patients on the waiting list, some centres are expanding their donor pool by relaxing the criteria, such as by using organs from elderly (> 60 years) brainstem-dead donors. In this study, we reviewed our experience of using elderly brain-dead donor livers, investigating the potential prognostic factors of the donor, and analysing the influence of donor age on early graft function and graft survival. METHODS: We retrospectively evaluated 106 cadaveric donor liver transplantations in 98 patients. Seven patients (6.6%, 7 vs 106) received livers from donors older than 60 years. Pre-transplantation characteristics of donors and the outcome of recipients were evaluated. Donor prognostic factors were analysed using Cox univariate analysis and confirmed by a multivariate forward stepwise Cox model. Early graft function was compared between recipients of grafts from donors older and younger than 60 years. RESULTS: There were no primary non-functions or re-transplants in the group receiving elderly grafts. Early graft function was similar in patients with grafts from elderly and younger donors. Univariate analysis demonstrated that prognostic factors had no relationship with long-term recipient survival. The 3-month and 1-year cumulative graft survival rates were 100% and 82% in the elderly graft group and 84% and 83% in the younger graft group, respectively. Kaplan-Meier curves and the log-rank test indicated that there was no difference in graft and patient survival rates between the two groups. CONCLUSIONS: Old age is not a contraindication for liver donation. Liver grafts from donors older than 60 years can be used safely.

Adolescent↗

PubMed2004

Sustained blockade of brain AT1 receptors before and after focal cerebral ischemia alleviates neurologic deficits and reduces neuronal injury, apoptosis, and inflammatory responses in the rat.

In the present study, we investigate whether a long-term blockade of brain AT1 receptors in male Wistar rats before and after ischemic injury exerts neuroprotective effects and modulates apoptosis and inflammatory responses, which are associated with the post-ischemic progression of brain damage. The AT1 receptor antagonist irbesartan was continuously infused intracerebroventricularly using osmotic minipumps over a 5-day period before and for 3 or 7 days after middle cerebral artery occlusion (MCAO) for 90 minutes. Neurologic status was evaluated daily, starting 24 hours after MCAO. After MCAO (3 and 7 days), brains were removed for the measurement of infarct size and immunohistochemical evaluation of apoptosis and accumulation of reactive microglia and macrophages. Treatment with irbesartan before ischemia improved motor functions, whereas post-ischemic treatment improved sensory functions. Blockade of brain AT1 receptors reduced the infarct size on days 3 and 7 after MCAO. In the peri-infarct cortex, irbesartan treatment decreased the number of apoptotic cells on day 3 and attenuated the invasion of activated microg-lia and macrophages on days 3 and 7 after ischemia. Long-term blockade of brain AT1 receptors improves the recovery from cerebral ischemia. Antiapoptotic mechanisms and inhibition of post-ischemic inflammation are involved in the AT1 receptor blockade-induced neuroprotective effects in ischemic brain tissue.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Polymorphism of renin-angiotensin system genes in IgA nephropathy.

BACKGROUND AND AIMS: Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact. METHODS: Genotyping was performed with DNA isolated from peripheral leucocytes, polymerase chain reaction amplification of the polymorphic sequence, restriction enzymes digestion, and separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. RESULTS: Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. In contrast, there were significant differences in higher male prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05), more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001) in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in the Chinese population. None are significant for prognosticating ESRF.

Adult↗

PubMed2004

Attenuation of small-for-size liver graft injury by FTY720: significance of cell-survival Akt signaling pathway.

To investigate the protective mechanism of FTY720 in small-for-size liver grafts, we applied a rat orthotopic liver transplantation model using 40% of liver grafts. FTY720 was administered (1 mg/kg, i.v.) at 20 min before graft harvesting in the donor, immediately before total hepatectomy and immediately after graft reperfusion in the recipient. The 7-day graft survival rates in the FTY720 group were significantly improved compared with the control group [100% (6/6) vs. 40% (4/10), p = 0.034]. FTY720 significantly reduced serum ALT and AST levels at 24 h after liver transplantation. The cell-survival Akt signaling pathway was activated in FTY720 groups by phosphorylation of Glycogen Synthase Kinase-3beta, Bad and Forkhead Transcription Factor at 6 and 24 h after liver transplantation. The cleaved-caspases 3, 7 and 9 were down-regulated, accompanied with less apoptotic nuclei after FTY720 treatment. Acute-phase inflammatory MAPK pathway was down-regulated by dephosphorylation of c-Raf, Mek and Erk in the treatment groups. A20 and endothelial nitric oxide synthase were up-regulated together with down-regulation of iNOS. Hepatic sinusoids were well preserved in the FTY720 group but disrupted in the control group. In conclusion, FTY720 attenuates small-for-size liver graft injury by activation of cell-survival Akt signaling and down-regulation of the MAPK pathway.

Alanine Transaminase↗

PubMed2004

Renin-angiotensin system gene polymorphisms: its impact on IgAN and its progression to end-stage renal failure among Chinese in Singapore.

BACKGROUND: Gene polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (ATR) had been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasian and Japanese had reported contradicting results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese to assess their clinical impact. METHODS: Genotyping was performed with DNA from peripheral leukocytes, PCR amplification of the polymorphic sequence, restriction enzymes digestion, separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. RESULTS: Among controls, genotype distributions were in Hardy-Weinberg equilibrium. Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar whereas there was significant increase in the ACE DD genotype (p < 0.05). Comparing patients with end-stage renal failure (IgAN-ESRF) and without (IgAN-nonESRF), there was no difference in any of the three gene polymorphisms. But in contrast, there were significant differences in higher male prevalence (p < 0.05), increased serum creatinine at presentation (p < 0.05), more sclerosis (p < 0.01) and higher tubulointerstitial lesion score (p < 0.001) in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in our Chinese population. In contrast to clinical and histological risk factors, these genetic variations showed no impact on disease progression to ESRF. It is unlikely that genotyping more patients will prove these genes useful. Nevertheless, preclinically determined genetic markers are very useful as risk factors for disease occurrence and as prognostic indices for disease progression. Therefore, continuing efforts should be made to look at other genes to find those with significance.

Adult↗

PubMed2004

Experimental study on the simultaneous desulfurization and denitrification by duct injection.

The highly active absorbent with oxidization based on fly ash, lime and additive was prepared. Experiments of simultaneous desulfurization and denitrification were carried out using fixture bed and duct injection. The influencial factors for the absorptive capacity of the absorbent were studied. The absorptive capacities of 120.7 mg for SO2 and 43.7 mg for NOx were achieved at a Ca/(S + N) molar ratio 1.2, respectively, corresponding removal efficiencies of 87% and 76%, while spent absorbent appeared in the form of dry powder. The optimal temperature and humidity of flue gas treated with this process were shown to be approximately 50 degrees C, and 5% respectively. The mechanism of removal for SO2 and NOx was investigated. In comparison with traditional dry FGD, this process appears to have lower cost, less complicated configuration and simpler disposal of used absorbent. The valuable references can be provided for industrial application by this process. The foreground of application will be vast in China and in the world.

Absorption↗

PubMed2004

[Resolution for the kinetic process of ultrasound-assisted electro-catalytic degradation of benzoic acid].

The two-way kinetic-spectral data can be acquired by monitoring the process of the ultrasound-assisted electro-catalytic degradation of benzoic acid. The product of absorbing intermediate is confirmed by FSMWEFA(Fix-sized Moving Window Evolving Factor Analysis). The real kinetic spectra and absorption spectra, which are hard to measure directly, are resolved by ITTFA (Iterative Target Transformation Factor Analysis) combined with the isoabsorptive points between components. The kinetic model of benzoic acid degradation is also studied.

Benzoic Acid↗