Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 163 records · Page 9Linked to original sources

PubMed2001

Analytical design and analysis of mismatched Smith predictor.

In this paper, an analytical design method is developed for the mismatched Smith predictor on the basis of the internal model control (IMC) method. Design formulas are given and design procedure is significantly simplified. One important merit of the proposed method is that the response of the closed loop system can be easily adjusted. The relation between the controller parameter and the system response is monotonous. In addition, necessary and sufficient condition for the robust stability of mismatched Smith predictor is also given. It is shown that the proposed method can provide good performance for perfectly matched system and a better response for mismatched system. Several numerical examples are given to illustrate the proposed method.

Journal Article↗

PubMed2001

Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-kappaB binding to its recognition sequence.

Cilostazol is a specific inhibitor of cAMP phosphodiesterase, which is used for treatment of ischemic symptoms of peripheral vascular disease. Although cilostazol has antiplatelet and vasodilator properties, its effect on the expression of adhesion molecules in vascular endothelium is not known. In the present investigation, we examined the effect of cilostazol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured vascular endothelial cells. Cilostazol strongly inhibited tumor necrosis factor (TNF)-alpha-induced expression of VCAM-1 protein and its mRNA. In addition, cilostazol reduced TNF-alpha-induced U937 cell adhesion to the vascular endothelial cells. In transient transfection studies, cilostazol inhibited TNF-alpha-induced transcriptional activation of VCAM-1 promoter. Electrophoretic mobility shift assays revealed that cilostazol repressed TNF-alpha-induced increase in binding of the transcription nuclear factor-kappaB (NF-kappaB) to its recognition site of VCAM-1 promoter. Cilostazol, however, failed to prevent nuclear translocation of the NF-kappaB p65 protein. These data indicate that cilostazol repressed VCAM-1 gene transcription in cultured vascular endothelial cells, via inhibiting NF-kappaB binding to its recognition sequence. Since the expression of the adhesion molecule is one of the earliest events occurred in atherogenic process, cilostazol might have the potential to prevent atherosclerosis at least via inhibition of the expression of the adhesion molecule.

Cell Adhesion↗

PubMed2001

Binding of anticoagulation factor II from the venom of Agkistrodon acutus with activated coagulation factor X.

Anticoagulation factor II (ACF II) from the venom of Agkistrodon acutus has been identified as a binding protein to activated bovine coagulation factor X (FXa) by the method of polyacrylamide gel electrophoresis and high performance liquid chromatography. This protein formed a 1:1 complex with FXa in the presence of Ca2+ ions, and the maximal binding of ACF II to FXa occurred at the concentration of Ca2+ ions of about 1mM. The binding of Ca2+ ions to ACF II was analyzed by equilibrium dialysis and two Ca2+-binding sites with different affinities were identified. At pH 8.0, the apparent association constant K1 and K2 values for these sites were (1.1+/-0.3)x10(5) M(-1) and (1.7+/-0.4)x10(4) M(-1) (mean+/-SE, n=4), respectively. It was evident from the observation of Ca2+-induced changes in the intrinsic fluorescence of ACF II that ACF II underwent a conformational change upon binding of Ca2+ ions. The occupation of both Ca2+-binding sites in ACF II requires a concentration of Ca2+ ions of about 1mM, which is equal to the effective concentration of Ca2+ ions required for maximal binding of ACF II to FXa, and for the maximal Ca2+-induced enhancement of emission fluorescence of ACF II. It can be deduced from these results that the occupation of both Ca2+-binding sites in ACF II with Ca2+ ions and subsequent conformational rearrangement should be essential for its recognition of Ca2+-mediated conformational changes of FXa.

Agkistrodon↗

PubMed2001

Activated CD8(+) T cells from aged mice exhibit decreased activation-induced cell death.

To uncouple the defects of activation and apoptosis of T cells from aged mice, we used anti-CD3 plus IL-2 stimulation to induce an activation response and analyzed the subsequent activation-induced cell death (AICD) response of T cells from 16-month-old mice. The results herein demonstrate that T cells from 16-month-old mice could be activated by anti-CD3-induced activation signals but exhibited distinct phenotypic and functional features compared to young (2-month-old) mice. These include a decrease in AICD, a delayed entry into the cell cycle, and a decreased telomerase activity. The decreased AICD of T cells from 16-month-old mice is associated with a decreased expression of Fas and Fas ligand (FasL), decreased susceptibility to anti-Fas-induced apoptosis, and an increased expansion of a CD8(+) T-cell population. Prior to activation, these T cells exhibit a phenotype that is CD44(hi)CD62L(hi). After stimulation, these T cells produced high levels of the pro-inflammatory cytokine, IFN-gamma, and developed an increased population of IFN-gamma(+)IFN-gamma R(-) T cells. Our results suggest that there is a dysregulation in T-cell homeostasis in aged mice associated with a decrease in AICD of CD8(+) T cells.

Aging↗

PubMed2001

The future of genetic case-control studies.

The case-control study design has been a veritable workhorse in epidemiological research since its inception and acceptance as a valid and valued field of inquiry. The reasons for this owe to the simplicity of the required sampling and the (potential) ease of analysis and interpretation of results. Unfortunately, there are a number of problems that plague the use of the case-control design in assessing relationships between genetic variation and disease susceptibility in the population at large. Many of these problems are entirely analogous to problems that inhere in applications of the case-control design in nongenetic settings. These problems include stratification, the assessment of statistical significance, heterogeneity, and the interpretation of multiple outcomes or phenotypic information. In this chapter we describe 10 problems thought to plague genetic case-control studies and offer potential solutions to each. Many of our proposed solutions require the use of multiple DNA markers to accommodate the genetic background of the individuals sampled as cases and controls. It is hoped that our discussions and proposals will spark further debate about the analysis and ultimate utility of the case-control study in genetic epidemiology research.

Case-Control Studies↗

PubMed2001

A new nerve guide conduit material composed of a biodegradable poly(phosphoester).

There is a resurgence of interest in the development of degradable and biocompatible polymers for fabrication of nerve guide conduits (NGCs) in recent years. Poly(phosphoester) (PPE) polymers are among the attractive candidates in this context, in view of their high biocompatibility, adjustable biodegradability, flexibility in coupling fragile biomolecules under physiological conditions and a wide variety of physicochemical properties. The feasibility of using a biodegradable PPE, P(BHET-EOP/TC), as a novel NGC material was investigated. Two types of conduits were fabricated by using two batches of P(BHET-EOP/TC) with different weight-average molecular weights (Mw) and polydispersity indexes (PI). The polymers as well as conduits were non-toxic to all six types of cells tested, including primary neurones and neuronally differentiated PC12 cells. After in situ implantation in the sciatic nerve of the rat, two types of conduits triggered a similar tissue response, inducing the formation of a thin tissue capsule composed of approximately eight layers of fibroblasts surrounding the conduits at 3 months. Biological performances of the conduits were examined in the rat sciatic nerve model with a 10 mm gap. Although tube fragmentation, even tube breakage, was observed within less than 5 days post-implantation, successful regeneration through the gap occurred in both types of conduits, with four out of 10 in the Type I conduits (Mw 14,900 and PI 2.57) and 11 out of 12 in the Type II conduits (Mw 18,900 and PI 1.72). The degradation of conduits was further evidenced by increased roughness on the tube surface in vivo under scanning electron microscope and a mass decrease in a time-dependent manner in vitro. The Mw of the polymers dropped 33 and 24% in the Type I and II conduits, respectively, in vitro within 3 months. Among their advantages over other biodegradable NGCs, the PPE conduits showed negligible swelling and no crystallisation after implantation. Thus, these PPE conduits can be effective aids for nerve regeneration with potential to be further developed into more sophisticated NGCs that have better control of the conduit micro-environment for improved nerve regeneration.

Animals↗

PubMed2001

Detection of prawn white spot bacilliform virus by immunoassay with recombinant antigen.

Prawn white spot bacilliform virus (WSBV) is the major pathogen of prawn disease. To develop a sensitive assay for the early detection of this virus, we generated an antibody against a WSBV-specific protein, P204. The p204 gene was cloned from a WSBV cDNA library and expressed in Escherichia coli. The peptide (P204) encoded by p204 was purified, and its antibody raised in mice. IgG fraction of the anti-P204 serum was purified using a Sepharose column and the Fab fragment was obtained by pepsin digestion. An enzyme-linked immunosorbent assay (ELISA) using this Fab fragment was developed to detect the WSBV in prawn tissues. The experiments showed that Fab of anti-P204 antibody is highly specific for WSBV, and displays a sensitivity of 10(5) viral particles/mg prawn tissues. This is the first report using the Fab fragment prepared from a recombinant antigen to detect prawn viruses by ELISA.

Animals↗

PubMed2001

Quantitative measurement of the nitrate reductase activity in the human oral cavity.

To quantitatively characterise the nitrate reductase activity in the human oral cavity, a new assay based on holding 20 ml of 10 mg nitrate-N/L solution in the mouth was developed. The mouth assay appeared to relate primarily to the oral cavity surface rather than to the saliva. Nitrite formation in the assay was 50-100 times higher compared to in vitro incubation. In the proposed assay, the nitrite formation linearly increased over a period of 3 min. The average nitrate reductase activity in the oral cavity of 20 subjects was 2.39+/-1.52 microg nitrite-N formed/person x min. The nitrate reductase activity measured for two subjects at different hours varied about 15% for the same subject. The average nitrate reductase activity measured in June for 10 subjects (3.43+/-1.75 microg-N/person x min) was significantly higher than that measured in November for 10 other subjects (1.54+/-0.46 microg-N/person x min). Therefore, the nitrate reductase activity in the oral cavity appears to be influenced by the seasonal conditions. Although the amounts of nitrite formed in the mouth assay increased with increasing levels of nitrate, the rate of nitrate to nitrite reduction decreased with increasing levels of nitrate. The nitrite formation was also affected by the pH, with an optimal pH about 8. The nitrite formation was not influenced by uptake in the mouth of glucose, L-ascorbic acid and L-arginine.

Adult↗

PubMed2001

Determination of degradation products of sumatriptan succinate using LC-MS and LC-MS-MS.

Acid, base, heat, oxidation and UV irradiation stress methods were applied to study the stability of the bulk drug form of sumatriptan succinate. Liquid chromatography coupled with mass spectrometry (LC-MS and LC-MS-MS) was used to analyze the degraded samples and tentative structural identifications were assigned based upon known reactivity of the drug, molecular weight measurements and MS-MS fragmentation patterns. Sumatriptan succinate was found to be stable to exposure of acid, base, oxidation and UV irradiation at ambient conditions, but was found to degrade under acidic, basic and oxidative conditions when heated to 90 degrees C.

Chromatography, Liquid↗

PubMed2001

Comparison of negative and positive ion electrospray tandem mass spectrometry for the liquid chromatography tandem mass spectrometry analysis of oxidized deoxynucleosides.

Oxidized deoxynucleosides are widely used as biomarkers for DNA oxidation and oxidative stress assessment. Although gas chromatography mass spectrometry is widely used for the measurement of multiple DNA lesions, this approach requires complex sample preparation contributing to possible artifactual oxidation. To address these issues, a high performance liquid chromatography (HPLC)-tandem mass spectrometric (LC-MS/MS) method was developed to measure 8-hydroxy-2'-deoxyguanosine (8-OH-dG), 8-hydroxy-2'-deoxyadenosine (8-OH-dA), 2-hydroxy-2'-deoxyadenosine (2-OH-dA), thymidine glycol (TG), and 5-hydroxy-methyl-2'-deoxyuridine (HMDU) in DNA samples with fast sample preparation. In order to selectively monitor the product ions of these precursors with optimum sensitivity for use during quantitative LC-MS/MS analysis, unique and abundant fragment ions had to be identified during MS/MS with collision-induced dissociation (CID). Positive and negative ion electrospray tandem mass spectra with CID were compared for the analysis of these five oxidized deoxynucleosides. The most abundant fragment ions were usually formed by cleavage of the glycosidic bond in both positive and negative ion modes. However, in the negative ion electrospray tandem mass spectra of 8-OH-dG, 2-OH-dA, and 8-OH-dA, cleavage of two bonds within the sugar ring produced abundant S1 type ions with loss of a neutral molecule weighing 90 u, [M - H - 90]-. The signal-to-noise ratio was similar for negative and positive ion electrospray MS/MS except in the case of thymidine glycol where the signal-to-noise was 100 times greater in negative ionization mode. Therefore, negative ion electrospray tandem mass spectrometry with CID would be preferred to positive ion mode for the analysis of sets of oxidized deoxynucleosides that include thymidine glycol. Investigation of the fragmentation pathways indicated some new general rules for the fragmentation of negatively charged oxidized nucleosides. When purine nucleosides contain a hydroxyl group in the C8 position, an S1 type product ion will dominate the product ions due to a six-membered ring hydrogen transfer process. Finally, a new type of fragment ion formed by elimination of a neutral molecule weighing 48 (CO2H4) from the sugar moiety was observed for all three oxidized purine nucleosides.

Animals↗

PubMed2001

Association of DDT with spontaneous abortion: a case-control study.

PURPOSE: Spontaneous abortion (SAB), the most common adverse pregnancy outcome, affects approximately 15% of clinically recognized pregnancies. Except for advanced maternal age and smoking, there are not well-established risk factors for SAB. Animal models associate increased fetal resorption or abortion with exposure to the pesticide dichlorodiphenyl trichloroethane (DDT), but epidemiologic investigations of DDT and SAB are inconsistent. We undertook a pilot investigation of the hypothesized association of DDT with SAB. METHODS: Participants in this case-control study were selected from a longitudinal study of reproductive effects of rotating shifts among female Chinese textile workers who were married, ages 22-34, nulliparous without history of SAB or infertility, and planning pregnancy. From 412 pregnancies, 42 of which ended in SAB, 15 SAB cases and 15 full-term controls were randomly selected and phlebotomized. Serum was analyzed for p,p'-DDT, o,p'-DDT, their metabolites (DDE and DDD), and other organochlorines including polychlorinated biphenyls. RESULTS: Cases and controls were nonsmokers and did not differ in age (mean 25 years), body mass index (BMI), passive smoke exposure, or workplace exposures. Cases had significantly (p < 0.05) higher serum levels of p,p'-DDE (22 vs.12 ng/g) and o,p'-DDE (0.09 vs. 0.05 ng/g) than controls. After adjustment for age and BMI, each ng/g serum increase in p,p'-DDE was associated with a 1.13 (CI, 1.02-1.26) increased odds of SAB. With adjustment of serum DDE levels for excretion via breastfeeding, DDE-associated increased odds of SAB remained significant with up to 7% declines in maternal serum DDE levels for each month of breastfeeding. CONCLUSIONS: A potential increased risk of SAB is associated with maternal serum DDE levels.

Abortion, Spontaneous↗

PubMed2001

A new molecular simulation software package--Peking University Drug Design System (PKUDDS) for structure-based drug design.

We present a comprehensive molecular simulation program package, the Peking University Drug Design System (PKUDDS), which runs on personal computers. PKUDDS has been developed mainly for computer-aided drug design using the methods of two-dimensional quantitative structure-activity relationships, three-dimensional quantitative structure-activity relationships, molecular docking, and database screening. This study presents an overview of its functionality, especially of methods developed in our group. PKUDDS uses genetic algorithms in molecular docking, conformational analysis, and quantitative structure-activity relationships as the most useful optimization technique. A user-friendly graphical interface provides easy access to many functions of PKUDDS. We report some examples of our considerable research using PKUDDS.

Antineoplastic Agents↗

PubMed2001

SC35 plays a role in T cell development and alternative splicing of CD45.

Molecular diversity via alternative splicing is important for cellular function and development. SR proteins are strong candidate regulators of alternative splicing because they can modulate splice site selection. However, endogenous substrates for SR proteins are largely unknown, and their roles as splicing regulators in vertebrate development are unclear. Here we report that Cre-mediated conditional deletion of the prototypical SR protein SC35 in the thymus causes a defect in T cell maturation. Deletion of SC35 alters alternative splicing of CD45, a receptor tyrosine phosphatase known to be regulated by differential splicing during thymocyte development and activation. This study establishes a model to address the function of SR proteins in physiological settings and reveals a critical role of SC35 in a T cell-specific regulated splicing pathway.

Alternative Splicing↗

PubMed2001

Synthesis of structured triacylglycerols containing caproic acid by lipase-catalyzed acidolysis: optimization by response surface methodology.

Production in a batch reactor with a solvent-free system of structured triacylglycerols containing short-chain fatty acids by Lipozyme RM IM-catalyzed acidolysis between rapeseed oil and caproic acid was optimized using response surface methodology (RSM). Reaction time (t(r)), substrate ratio (S(r)), enzyme load (E(l), based on substrate), water content (W(c), based on enzyme), and reaction temperature (T(e)), the five most important parameters for the reaction, were chosen for the optimization. The range of each parameter was selected as follows: t(r) = 5-17 h; E(l) = 6-14 wt %; T(e) = 45-65 degrees C; S(r) = 2-6 mol/mol; and W(c) = 2-12 wt %. The biocatalyst was Lipozyme RM IM, in which Rhizomucor miehei lipase is immobilized on a resin. The incorporation of caproic acid into rapeseed oil was the main monitoring response. In addition, the contents of mono-incorporated structured triacylglycerols and di-incorporated structured triacylglycerols were also evaluated. The optimal reaction conditions for the incorporation of caproic acid and the content of di-incorporated structured triacylglycerols were as follows: t(r) = 17 h; S(r) = 5; E(l) = 14 wt %; W(c) = 10 wt %; T(e) = 65 degrees C. At these conditions, products with 55 mol % incorporation of caproic acid and 55 mol % di-incorporated structured triacylglycerols were obtained.

Brassica↗

PubMed2001

Tetranectin in slow intra- and extrafusal chicken muscle fibers.

Tetranectin is a C-type lectin that occurs in the mammalian musculoskeletal system. In the present report we describe the first studies on an avian tetranectin. A full-length chicken tetranectin cDNA was isolated. Comparison of the deduced amino acid sequence of chicken tetranectin with mouse and human tetranectin showed an identity of 67 and 68%, respectively. Northern blot analysis demonstrated broad expression of chicken tetranectin mRNA, which was first detected on embryonic day 4. Tetranectin protein was detected in chicken serum and egg yolk. Since muscle is one of few tissues in which tetranectin protein is retained, we examined the distribution of tetranectin in various muscle types in chicken. Myofibers strongly positive for tetranectin were observed in several muscles including m. tibialis ant. and m. sartorius (from embryonic day 10 to adult). Using antibodies to fast and slow myosin heavy chains (MHC) and double immunostaining techniques, we found that tetranectin was restricted to slow (type I) muscle fibers. Similarly only slow intrafusal fibers accumulated tetranectin. The pattern of immunostaining in chickens differs markedly from that seen in mouse muscles, indicating that tetranectin performs a role in muscle that is not associated with a hitherto recognized muscle type or function.

Adaptation, Physiological↗

PubMed2001

The effect of calcium (II) on the binding of anticoagulation factor I with activated coagulation factor X.

Anticoagulation factor I (ACF I) from the venom of Agkistrodon acutus forms a 1:1 complex with activated coagulation factor X (FXa) in a Ca2+-dependent fashion and thereby prolongs the clotting time. In the present study, the dependence of the binding of ACF I with FXa on the concentration of Ca2+ ions was quantitatively analyzed by HPLC, and the result showed that the maximal binding of ACF I to FXa occurred at concentration of Ca2+ ions of about 1 mM. The binding of Ca2+ ions to ACF I was investigated by equilibrium dialysis and two Ca2+-binding sites with different affinities were identified. At pH 7.6, the apparent association constants K1 and K2 for these two sites were (1.8 +/- 0.5) x 10(5) and (2.7 +/- 0.6) x 10(4) M(-1) (mean +/- SE, n = 4), respectively. It was evident from the observation of Ca2+-induced changes in the intrinsic fluorescence of ACF I that ACF I underwent a conformational change upon binding of Ca2+ ions. The occupation of both Ca2+-binding sites in ACF I required a concentration of Ca2+ ions of about 1 mM, which is equal to the effective concentration of Ca2+ ions required both for maximal binding of ACF I to FXa and for the maximal enhancement of emission fluorescence of ACF I. It could be deduced from these results that the occupation of both Ca2+-binding sites in ACF I with Ca2+ ions and subsequent conformational rearrangement might be essential for the binding of ACF I to FXa.

Binding Sites↗

PubMed2001

The interaction of azide with polyphenol oxidase II from tobacco.

Spectroscopy studies of absorption and circular dichroism of native PPO II and azide PPO II complex demonstrate two new absorptions at 375 nm and 500 nm after azide's binding with PPO II, which are assigned as the terminal azide to copper charge transfer transitions II(o)nb-to-copper and II(v)nb-to-copper charge transfer transitions respectively. FT-IR spectra also demonstrate that the azide binds in terminal geometry with one of type-3 coppers. The interaction between azide and PPO II is discussed. One terminal azide's binding with one type-3 copper improves the activity of PPO II and the other three azides' further binding in terminal geometry with the type-3 coppers decreases the activity. We theorize that steric hindrance of azides makes oxygen difficult to bind in the active site.

Azides↗

PubMed2001

Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats.

The urotoxicity of cyclophosphamide and the protective effect of the herb berberine were investigated in this study. Administration of 150 mg/kg cyclophosphamide intraperitoneally caused a serious haemorrhagic cystitis in rats after 12 hr, including bladder oedema, haemorrhage, and dramatic elevation of nitric oxide metabolites (nitrite+nitrate) in urine and in plasma. To explore whether cyclophosphamide-induced cystitis could be prevented by berberine, rats were pretreated with a single dose or two doses of berberine at 50, 100, or 200 mg/kg intraperitoneally then challenged with cyclophosphamide (150 mg/kg, intraperitoneally). The results indicated that pretreatment of rats with berberine could reduce cyclophosphamide-induced cystitis in a dose-dependent manner. Furthermore, we found that two doses of berberine showed greater protection against cyclophosphamide urotoxicity than when given a single dose. In addition, our data shows that a single dose of 200 mg/kg berberine, or two doses of 100, and 200 mg/kg berberine could completely block cyclophosphamide-induced bladder oedema and haemorrhage, as well as nitric oxide metabolites increase in rat urine and plasma. In conclusion, our findings suggest that berberine could be a potential effective drug in the treatment of cyclophosphamide-induced cystitis, and provides us with the bright hope in the prevention and treatment of cyclophosphamide urotoxicity.

Animals↗