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Biomedical subjects

Y Mao

Publications and source records attributed to Y Mao.

At least 55 records · Page 3Linked to original sources
PubMed2001

Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system.

To explore the hypothesis that insulin resistance may be an etiologic factor in pancreatic cancer, we assessed the pancreatic cancer risk associated with anthropometric factors and physical activity, both of which are important determinants of insulin sensitivity in humans. Three hundred and twelve patients with histologically confirmed pancreatic cancer were compared to 2,919 controls in a population-based, case-control study in 7 of the 10 Canadian provinces. Participants were asked to report their exposure status for the period 2 years before interview. Men in the highest quartile of body mass index (BMI, > or =28.3 kg/m(2)) were at increased risk of pancreatic cancer [adjusted odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.08-3.35]. In addition, men who reported a decrease in weight of at least 2.9% from their lifetime maximum were at reduced risk compared to those reporting a < or =2.9% loss (> or =10.2% loss, OR = 0.51, 95% CI 0.30-0.86). BMI 2 years before interview was not associated with pancreatic cancer risk among women, though those reporting a > or =12.5% decrease in weight from their lifetime maximum had substantially lower risk compared to those in the baseline quartile (OR = 0.53, 95% CI 0.29-0.99). After adjustment for age, province of residence, dietary intake and anthropometric factors, men in the highest quartile of the composite moderate and strenuous physical activity index were at reduced risk of pancreatic cancer (OR = 0.53, 95% CI 0.31-0.90). Physical activity did not appear to be associated with pancreatic cancer among women, though a tendency for reduced risk with increasing levels of strenuous activity was suggested (p for trend = 0.06). Our findings support the hypothesis that insulin resistance is an etiologic factor in the development of pancreatic neoplasms among men and possibly women.

Age Factors↗
PubMed2001

Cholesteric elastomers: deformable photonic solids.

A mechanical strain applied to a monodomain cholesteric elastomer modulates and eventually unwinds the helical director distribution. There are similarities with the classical problem of an electric field applied to a cholesteric liquid crystal, but also differences. Frank elasticity is of minor importance unless the gel is very weak. The interplay is rather between the director being helically anchored to the rubber elastic matrix and the external mechanical field. Stretching perpendicular to the helix axis induces the uniform unwound state via the elimination of sharp, pinned twist walls above a critical strain. Below the critical strain the coarsening of the director distribution is not accompanied by an increase but rather by an affine decrease in the pitch. Unwinding through conical director states occurs when the elastomer is stretched along the helical axis. Finally we consider cholesteric elastomers in a classical device geometry with an electric field applied along the pitch axis and hence transverse to the director orientation.

Journal Article↗
PubMed2001

Separation of selected basic pharmaceuticals by reversed-phase and ion-exchange chromatography using thermally tuned tandem columns.

The separation of basic pharmaceuticals is usually performed on C8 or C18 bonded silica supports. Silanolphilic interactions between basic analytes and surface silanol groups often lead to tailed peaks, poor efficiency, and irreproducible retention times. To solve these problems, many new types of silica-, zirconia-, and polymer-based columns, which provide unique selectivities, improved stability at high pH, or both, have been developed for the analysis of basic compounds. The essence of method development for the chromatographic analysis of basic compounds is to choose a system in which the band spacing can be varied dramatically, quickly, and conveniently while minimizing the tailing due to silanolphilic interactions. The thermally tuned tandem column (T3C) approach has been shown to provide an effective way to adjust stationary-phase selectivity for nonionic compounds. In this study, a tandem combination of an octadecylsilane (ODS) and a polybutadiene-coated zirconia (PBD-ZrO2) phase was used to separate nine antihistamines. Selectivity is tuned by independently adjusting the isothermal temperatures of the two columns. We found dramatic differences in the retention factors, elution sequences, and band spacing for the above set of basic drugs on the two types of columns. The T3C model has been used successfully to locate the optimal temperatures based on only four exploratory runs. The nine antihistamines were baseline separated on the tandem column combination even though they could not be separated on the individual phases. The effect of the buffer concentration on retention of the basic antihistamines was also studied. We conclude that cation-exchange interactions predominate on the PBD-ZrO2 phase, while reversed-phase interactions are more important on the ODS phase. Interestingly, an increase in column temperature causes a significant increase in the retention on the ODS column and a decrease of retention on the PBD-ZrO2 column. This can be explained by the change in the analyte's degree of ionization with temperature. The T3C combination of silica- and zirconia-based RPLC columns is demonstrated to be a powerful approach for the separation of this mixture of basic analytes.

Buffers↗
PubMed2001

26 S proteasome-mediated degradation of topoisomerase II cleavable complexes.

DNA topoisomerase II (TOP2) cleavable complexes represent an unusual type of DNA damage characterized by reversible TOP2-DNA cross-links and DNA double strand breaks. Many antitumor drugs and physiological stresses are known to induce TOP2 cleavable complexes leading to apoptotic cell death and genomic instability. However, the molecular mechanism(s) for repair of TOP2 cleavable complexes remains unclear. In the current studies, we show that TOP2 cleavable complexes induced by the prototypic TOP2 poison VM-26 are proteolytically degraded by the ubiquitin/26 S proteasome pathway. Surprisingly the TOP2beta isozyme is preferentially degraded over TOP2alpha isozyme. In addition, transcription inhibitors such as 5,6-dichlorobenzimidazole riboside and camptothecin can substantially block VM-26-induced TOP2beta degradation. These results are consistent with a model in which the repair of TOP2beta cleavable complexes may involve transcription-dependent proteolysis of TOP2beta to reveal the protein-concealed double strand breaks.

Animals↗
PubMed2001

Pyridopyrimidine analogues as novel adenosine kinase inhibitors.

A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.

Adenosine Kinase↗
PubMed2001

Monitoring for adsorption of human serum albumin and bovine serum albumin onto bare and polystyrene-modified silver electrodes by quartz crystal impedance analysis.

The adsorption of human serum albumin (HSA) and bovine serum albumin (BSA) from PBS (pH 7.4) onto bare and polystyrene (PS)-modified silver electrodes was in situ monitored using quartz crystal impedance analysis. The adsorption characteristics of HSA and BSA were discussed by analyzing piezoelectric parameter simultaneous responses. Experimental results indicated that for both HSA and BSA, the amount adsorbed on bare silver was more than that on PS-modified surface. The BSA amount adsorbed on the two surfaces was more than that of adsorbed HSA. A kinetic model was developed to describe the adsorption process and fitted to the experimental data of frequency shift. It was shown that HSA adsorption could be described by a kinetic equation involving two consecutive reactions. At lower concentration, BSA adsorption only involved the first reaction. At higher concentration, BSA adsorption on PS-modified surface involved two consecutive reactions. All fitted results were well in agreement with the corresponding experimental results. The regression values of reaction rate constants for the HSA and BSA adsorption were obtained. These data exhibited difference in adsorption kinetics under different conditions.

Adsorption↗
PubMed2001

Molecular dynamics simulations of the rehydration of folded and unfolded cytochrome C ions in the vapor phase.

Molecular dynamics (MD) simulations have been performed to study the rehydration of compact and unfolded cytochrome c ions in the vapor phase. Experimental studies have shown that the compact conformations adsorb many more water molecules than unfolded ones when exposed to water vapor. MD simulations performed with up to 150 water molecules reproduce the key experimental observations, including a partial refolding caused by hydration. According to the calculations it is more energetically favorable to hydrate the compact conformation in the initial stages of hydration, because it is easier for a water molecule to interact simultaneously with several polar groups (due to their proximity). The protonated side chains are not favored hydration sites in the simulations because they have "self-solvation" shells which must be disrupted for the water to penetrate. For both conformations, the adsorbed water molecules are mainly located in surface crevices.

Computer Simulation↗
PubMed2001

Imprinted networks as chiral pumps.

We investigate the interaction between a chirally imprinted network and a solvent of chiral molecules. We find that a liquid-crystalline polymer network is preferentially swollen by one component of a racemic solvent. This ability to separate is linked to the chiral order parameter of the network, and can be reversibly controlled via temperature or a mechanical deformation. It is maximal near the point at which the network loses its imprinted structure. One possible practical application of this effect would be a mechanical device for sorting mixed chiral molecules.

Models, Chemical↗
PubMed2001

Cloning and expression pattern of the human NDRG3 gene.

We report the cloning and expression pattern of a novel N-myc downstream-regulated gene 3 (NDRG3), located on human chromosome 20q11.21-11.23. The NDRG3 cDNA is 2588 base pair in length, encoding a 363 amino acid polypeptide highly related to mouse Ndr3 protein. Northern blot reveals that NDRG3 is highly expressed in testis, prostate and ovary. By in situ hybridization, the NDRG3 mRNA was localized to the outer layers of seminiferous epithelium, indicating that it may play a role in spermatogenesis.

Amino Acid Sequence↗
PubMed2001

Catalytic inhibition of DNA topoisomerase IIalpha by sodium azide.

It has been demonstrated previously that sodium azide reduces the clastogenicity of several DNA topoisomerase II (topo II) poisons in cultured mammalian cells. These studies suggested that azide may be a catalytic topo II inhibitor. Azide interferes with mitochondrial production of ATP and is also known to inhibit cellular ATPases. Since topo II requires ATP for catalytic activity (enzyme turnover), it seemed likely that interference with ATP levels or ATP catabolism was the underlying mechanism of topo II inactivation; however, this has not been examined in living cells under conditions where the endogenous topo II is active on genomic DNA. The present studies were carried out to verify that azide inhibits endogenous topo II in cells. We show that azide blocks both decatenation and relaxation activity of purified topo II in a concentration dependent manner and reduces topoII/DNA covalent complex formation in cells. From these studies, it is concluded that sodium azide catalytically inactivates topo II via an ATP-sensitive process.

Antigens, Neoplasm↗
PubMed2001

Separation of barbiturates and phenylthiohydantoin amino acids using the thermally tuned tandem column concept.

There are many more choices of column type than of eluent type for method development in reversed-phase liquid chromatography. It is common to switch between different column types or between the same type from different suppliers to achieve the desired separations. The key difficulty in modulating band spacing by adjusting the column type is that it is a discontinuous, "hit or miss" proposition. The thermally tuned tandem column (T3C) concept effectively solves this problem by connecting two columns in series and independently controlling the two column temperatures. The columns are chosen to have distinctively different chromatographic selectivities (band spacing), so that the unresolved peaks on one column are separated by the other. The optimized separation in the T3C is achieved by simultaneously tuning the two column temperatures. In this study, we used the T3C combination of a carbon and a conventional bonded phase for the separation of barbiturates and phenylthiohydantoin amino acids (PTH-amino acids). Good peak shapes and comparable retention times were observed on the two phases at room temperature. The selectivities on the two phases are quite different. Baseline separations were easily achieved with the T3C set although neither column could individually resolve all the peaks. We further compared the separation of barbiturates optimized by the T3C approach with that optimized by adjusting the mobile phase. We found that T3C gave a better separation. We believe that the T3C combination of a carbon phase and a bonded conventional reversed-phase material provides a powerful and general method to optimize the separation of various mixtures.

Algorithms↗
PubMed2001

Transcriptional adaptor and histone acetyltransferase proteins in Arabidopsis and their interactions with CBF1, a transcriptional activator involved in cold-regulated gene expression.

The ARABIDOPSIS CBF transcriptional activators bind to the CRT/DRE regulatory element present in the promoters of many cold-regulated genes and stimulate their transcription. Expression of the CBF1 proteins in yeast activates reporter genes carrying a minimal promoter with the CRT/DRE as an upstream regulatory element. Here we report that this ability of CBF1 is dependent upon the activities of three key components of the yeast Ada and SAGA complexes, namely the histone acetyltransferase (HAT) Gcn5 and the transcriptional adaptor proteins Ada2 and Ada3. This result suggested that CBF1 might function through the action of similar complexes in ARABIDOPSIS In support of this hypothesis we found that ARABIDOPSIS has a homolog of the GCN5 gene and two homologs of ADA2, the first report of multiple ADA2 genes in an organism. The ARABIDOPSIS GCN5 protein has intrinsic HAT activity and can physically interact in vitro with both the ARABIDOPSIS ADA2a and ADA2b proteins. In addition, the CBF1 transcriptional activator can interact with the ARABIDOPSIS GCN5 and ADA2 proteins. We conclude that ARABIDOPSIS encodes HAT-containing adaptor complexes that are related to the Ada and SAGA complexes of yeast and propose that the CBF1 transcriptional activator functions through the action of one or more of these complexes.

Acetyltransferases↗
PubMed2001

[Microsurgery of brainstem cavernous malformation].

OBJECTIVE: To evaluate the effectiveness and benefits of surgical treatment of cavernous malformations (CMs) in brainstem. METHODS: From 1992 to 1999, 7 cases of brainstem cavernous malformations (six females and one male, aged 44 on average) with 6 lesions in pons, one in mesencephalon, and one in medulla oblongata, were operated on with microsurgery. In the recent three years neuronavigation system has been applied. RESULTS: All of the eight lesions were removed without death toll. The functional disorders of nervous system were improved after operation in four cases. The neurological deficits worsened in two cases, however, their neurological functions improved gradually to the preoperative level in four months or three years. The neurological function in the case with lesion in mesencephalon worsened after operation. Pathology revealed a grade one oligodendroglioma in addition to the CM lesion. Neuronavigation helped facilitate the accurate location of the lesions and minimize the surgical injury. CONCLUSION: Microsurgery is effective in treating brainstem cavernous malformations with appropriate indications and minimal invasive technique.

Adult↗
PubMed2001

Stimulation of topoisomerase II-mediated DNA damage via a mechanism involving protein thiolation.

The breakage/reunion reaction of DNA topoisomerase II (TOP2) can be interrupted by DNA intercalators (e.g., doxorubicin), enzyme binders (e.g., etoposide), or DNA lesions (e.g., abasic sites) to produce TOP2-mediated DNA damage. Here, we demonstrate that thiol alkylation of TOP2 can also produce TOP2-mediated DNA damage. This conclusion is supported by the following observations using purified TOP2: (1) Thiol-reactive quinones were shown to induce TOP2-mediated DNA cleavage. (2) Thiol-reactive compounds such as N-ethylmaleimide (NEM), disulfiram, and organic disulfides [e.g., 2,2'-dithiobis(5-nitropyridine)] were also shown to induce TOP2-mediated DNA cleavage with similar reaction characteristics as thiol-reactive quinones. (3) TOP2-mediated DNA cleavage induced by thiol-reactive quinones was completely abolished using mutant yeast TOP2 with all cysteine residues replaced with alanine (cysteineless TOP2). These results suggest the possibility that cellular DNA damage could occur indirectly through thiolation of a nuclear protein, TOP2. The implications of this reaction in carcinogenesis and apoptotic cell death are discussed.

Alanine↗
PubMed2001

Molecular cloning, mapping and characterization of the human neurocalcin delta gene (NCALD).

We identified a new human gene that encodes a cognate of the bovine neurocalcin delta from a human fetal brain cDNA library; hence we named it human neurocalcin delta (NCALD) gene. The deduced polypeptide product of the cDNA is 22 kDa in size, and its amino acid sequence is 100% and 99% identical to that of the bovine and chicken neurocalcin, respectively. Northern blots showed that the NCALD gene is more abundantly expressed in brain, testis, ovary and small intestine. Tissue in situ hybridization confirmed the existence of the NCALD mRNA in the adult human testis. Radiation hybrid panel mapping localized the gene to chromosome 8 between molecular markers D8S270 and D8S257.

Adult↗