Clinical pharmacology of lasofoxifene in Japanese and white postmenopausal women.
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Aged↗
Biomedical subjects
G Wei
Publications and source records attributed to G Wei.
Immobilization and condensation of DNA with 3-aminopropyltriethoxysilane studied by atomic force microscopy.
We used different methods to modify a mica surface with 3-aminopropyltriethoxysilane (APTES), and then used it as substrate to immobilize DNA for atomic force microscopy (AFM) observation. The evaporation method and solution modifying method were investigated and evaluated. The solution modifying method was found to be relatively simple and effective. Using an APTES solution-modified mica surface, DNA immobilization appeared more reproducible and it could be imaged in liquid. The mixed solution of APTES and DNA was dropped directly onto the mica surface for AFM imaging. We found that DNA can condense in APTES water solutions. Toroids, rods and intermediate structures of condensation were captured by AFM.
DNA↗
Enhanced intracellular glutathione synthesis and excretion capability of Candida utilis by using a low pH-stress strategy.
AIMS: To study the effect of low pH stress on glutathione (GSH) synthesis and excretion capability of GSH fermentation production in Candida utilis. METHODS AND RESULTS: When C. utilis WSH 02-08 was cultivated in a glucose-ammonium sulfate medium without pH control, GSH leakage occurred when the pH of the medium decreased to 1.5. However, analysis of the cell viability indicated that the cells were not lysed. To further study the effect of low pH stress on GSH production, pH-controlled batch cultures were conducted, where the pH was switched from 5.5 to 1.2 at 24 h and maintained at 1.2 for 6 h. Nearly all intracellular GSH was leaked into the medium and the cell viability decreased dramatically, conceiving a long-term exposure of strain WSH 02-08 at low pH environment led to a complete cell lysis. A critical point (treated at pH 1.2 for 3 h) was experimentally determined, where most cells were alive but suffering a low pH stress. Low pH-stressed C. utilis cells displayed an increased intracellular GSH synthesis and export capability, which protected the cells against short-term low pH treatment. CONCLUSIONS: Using this knowledge, a low pH-stress strategy was developed and applied in fed-batch production of GSH and 197.3 mg l-1 of GSH was secreted into the medium. The GSH-specific production yield could be increased from 2.11 to 2.67% (w/w), and the total GSH concentration could reach 737.1 mg l-1 and increased by 24.9%. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of GSH secretion of C. utilis at low pH. This study demonstrated the importance of the physiology-based fermentation strategy in the production of useful metabolites.
Candida↗
Characterization of extracellular accumulation of Zn2+ during ischemia and reperfusion of hippocampus slices in rat.
The mammalian CNS contains an abundance of chelatable zinc that is sequestered in the vesicles of glutamatergic presynaptic terminals and co-released with glutamate. Considerable Zn(2+) is also released during cerebral ischemia and reperfusion (I/R) although the mechanism of this release has not been elucidated. We report here the real time observation of increase of the concentration of extracellular Zn(2+) ([Zn(2+)](o)), accompanied by a rapid increase of intracellular free Zn(2+)concentration, in the areas of dentate gyrus (DG), CA1 and CA3 in acute rat hippocampus slices during ischemia simulated by deprivation of oxygen and glucose (OGD) followed by reperfusion with normal artificial cerebrospinal fluid. A brief period of OGD caused a sustained increase of [Zn(2+)](o). Subsequent reperfusion with oxygenated medium containing glucose resulted in a further increase of [Zn(2+)](o). Longer periods of OGD caused greater increases of [Zn(2+)](o,) and subsequent reperfusion caused still further increases of [Zn(2+)](o,) regardless of OGD duration. The Zn(2+) chelator CaEDTA (10 mM) significantly reduced the increase of [Zn(2+)] induced by OGD and reperfusion. Significant regional differences of [Zn(2+)](o) over the areas of the DG, CA1 and CA3 were not observed during I/R. Neither sodium channel blockade by tetrodotoxin (2 microM), perfusion with nominally calcium-free medium nor anatomical disassociation of the DG, CA1 and CA3 regions from one another by lesioning affected the increase of [Zn(2+)](o). The non-specific nitric oxide synthase (NOS) inhibitor, Nomega-nitro-l-arginine methyl ester (1 mM), however, blocked the increase of [Zn(2+)](o) during ischemia and reperfusion. The data indicate the important role of NO in causing the release of Zn(2+) during I/R and suggest that NOS inhibitors may be used to reduce Zn(2+)-induced neuronal injury.
Anesthetics, Local↗
Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers.
We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients.
Aged↗
Immune elimination of Leishmania major in mice: implications for immune memory, vaccination, and reactivation disease.
Infection of susceptible BALB/c mice with a large, moderate, or low number of Leishmania major parasites respectively results in progressive disease, the formation of substantial but stable lesions, denoted as borderline disease, and the absence of a visible lesion. Infection with a low number of parasites results over the long term in either subclinical infections or an asymptomatic state. Subclinical mice produce a predominant Th1 response and are resistant to challenge, in contrast to their asymptomatic counterparts. Statistical and other evidence suggest that the asymptomatic state can arise from a subclinical state following parasite clearance, with consequent loss of resistance. Cell transfer studies demonstrate unequivocally that immune cells from subclinical mice can protect naive mice against a pathogenic challenge and can clear the parasite, leaving the mice susceptible to a rechallenge infection. This susceptibility is associated with the disappearance of both parasite-specific effector and memory T cells from secondary lymphoid organs. These findings have implications for vaccination, maintenance of memory, and prevention of reactivation disease.
Adoptive Transfer↗
The effect of precursor structures on the action of glucosaminyl 3-O-sulfotransferase-1 and the biosynthesis of anticoagulant heparan sulfate.
To understand how 2-O-sulfation of uronic acid residues influences the biosynthesis of anticoagulant heparan sulfate, the cDNA encoding glucosaminyl 3-O-sulfotransferase-1 (3-OST-1) was introduced into wild-type Chinese hamster ovary cells and mutant pgsF-17 cells, which are defective in 2-O-sulfation. 3-OST-1-transduced cells gained the ability to bind to antithrombin. Structural analysis of the heparan sulfate chains showed that 3-OST-1 generates sequences containing GlcUA-GlcN(SO(3))3(SO(3)) and GlcUA-GlcN(SO(3))3(SO(3))6(SO(3)) in both wild-type and mutant cells. In addition, IdoUA-GlcN(SO(3))3(SO(3)) and IdoUA-GlcN(SO(3))3(SO(3))6(SO(3)) accumulate in the mutant chain. These disaccharides were also observed by tagging [6-(3)H]GlcN-labeled pgsF-17 heparan sulfate in vitro with [(35)S]PAPs and purified 3-OST-1. Heparan sulfate derived from the transduced mutant also had approximately 2-fold higher affinity for antithrombin than heparan sulfate derived from the transduced wild-type cells, and it inactivated factor Xa more efficiently. This study demonstrates for the first time that (i) 3-O-sulfation by 3-OST-1 can occur independently of the 2-O-sulfation of uronic acids, (ii) 2-O-sulfation usually occurs before 3-O-sulfation, (iii) 2-O-sulfation blocks the action of 3-OST-1 at glucosamine residues located to the reducing side of IdoUA units, and (iv) that alternative antithrombin-binding structures can be made in the absence of 2-O-sulfation.
Animals↗
Immunohistochemical localization of interleukin-2 and its receptor subunits alpha, beta and gamma in the main olfactory bulb of the rat.
Endogenous interleukin-2 (IL-2) was found in the adult rat brain, however, it has not been reported whether this cytokine is present in the olfactory bulb. Immunohistochemical techniques were used to examine the cellular localization of IL-2 and its receptor subunits in the main olfactory bulb of the rat. Strong IL-2 immunoreactivity was localized in glial cells, specifically in the olfactory nerve layer, glomerular layer and external plexiform layer. IL-2 mRNA was detected in the olfactory bulb by RT-PCR. All three IL-2 receptor subunits also showed distinct laminar distributions. The IL-2Ralpha and IL-2Rbeta immunoreactivity was found both in neurons and glial cells, whereas IL-2Rgamma imunoreactivity was found in glial cells, and thus resembled IL-2 immunostaining. The present results demonstrated a wide distribution of IL-2 and its receptor subunits in the main olfactory bulb of the rat, suggesting that IL-2 might play a role in the olfactory function through autocrine or paracrine pathways. The exclusive high expression of IL-2 in glial cells in distinct laminar structures, where neuron-glia interactions are closely associated with olfactory nerve regeneration, imply that IL-2 might be involved in the process of nerve regeneration in the olfactory bulb.
Animals↗
Myocardial contractile responsiveness to endothelin-1 in the post-infarction rat model of heart failure: effects of chronic quinapril.
Cardiac endothelin-1 (ET-1) levels and ET receptor expression are increased in congestive heart failure (CHF). In order to determine whether this results in increased responsiveness of ET-A or ET-B receptors to ET-1, we evaluated the contractile effects of ET-1 in isolated papillary muscles isolated from hearts of control rats and from rats 4 weeks post myocardial infarction (MI) having received no therapy or chronic quinapril therapy. The ET-1 dose-response was biphasic in normal muscles. The use of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 revealed that the initial decrease in tension was the result of ET-B receptor stimulation. Blockade of nitric oxide (NO) production with L-NAME abolished the initial decrease in tension. MI resulted in CHF that was partially reversed by quinapril. In MI, the positive inotropic effects of ET-1 were enhanced due to the loss of the initial ET-B receptor mediated decrease in tension, as well as an increase in the positive inotropic effects of ET-A receptors. This was associated with an increase in ET-A and ET-B receptor mRNA and a decrease in cardiac ecNOS protein. Four weeks of therapy with quinapril attenuated the positive inotropic effects of ET-1 and prevented the increase in ET-A receptor mRNA. Although quinapril did not restore the effects of ET-B receptor stimulation or prevent the increase in ET-B mRNA, it did restore cardiac ecNOS protein expression. Thus, the inotropic response to ET-1 is biphasic due to an overall positive inotropic effect of ET-A receptor stimulation and an ET-B receptor mediated decrease in contractility at low ET-1 concentrations which appears to be mediated by cardiac ecNOS (NO). In post-MI CHF, responsiveness to ET-A receptors increases and the ET-B mediated negative inotropic response is lost despite an increase in both receptor subtypes. Quinapril therapy attenuates these effects and normalises cardiac ecNOS protein.
Angiotensin-Converting Enzyme Inhibitors↗
Effect of diazepam on the contents of amino acids and free radical during ischemia/reperfusion injury.
The protective effect and mechanism of diazepam on ischemia neurons during cerebral ischemia and reperfusion were studied. Sixty-three Wistar rats were divided randomly into nine groups: control group (n = 7), ischemia (is) groups including subgroups of is3 h, is3-h/rep1-h, is3-h/rep2-h, is3-h/rep3-h(n = 7 in each group), diazepam treated groups (10 mg/kg, i.p.), including subgroups of is3-h, is3-h/rep1-h, is3-h/rep2-h, is3-h/rep3-h (n = 7 in each group) with Zea longa's animal model of middle cerebral artery occlusion. The comparison between the ischemia group and diazepam-treated group showed that diazepam could obviously decrease the production of glutamate, asparate, MDA and increase the synthesis and release of GABA, SOD and GSH-PX. It was concluded that diazepam exerted its protective effects on neurons through complex mechanisms of regulating the synthesis and release of excitotary/inhibitory amino acids and free radicals.
Amino Acids↗
Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections.
The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.
AIDS Vaccines↗
A case for a neonatal, low-dose BCG vaccination trial.
The rational design of a successful vaccination strategy against tuberculosis requires certain kinds of information and must take account of several considerations: (i) the nature of the immune response that protects the large majority of individuals infected by Mycobacterium tuberculosis, designated as healthy contacts, must be defined and distinguished from that in tuberculosis patients, whose immune system must have failed; (ii) the vaccination strategy must incorporate a way of priming the immune system to guarantee in all individuals this protective response, normally generated in healthy contacts, upon natural infection by M. tuberculosis; (iii) the strategy must incorporate a mechanism for ensuring that the effectiveness of this priming is not abrogated by exposure to environmental mycobacteria; and (iv) the strategy must take account of the fact that the vaccinated population is genetically heterogeneous, and that individuals will therefore respond variably to most standard vaccination protocols. We describe a tentative proposal for how these interrelated problems might be solved and discuss predictions of this tentative vaccination strategy. Critical testing of the neonatal, low-dose BCG vaccination strategy can only be achieved by a field trial and we outline the considerations underlying this proposal.
Animals↗
Preparation and some physicochemical properties of cross-linked poloxamer hydrogel spheres.
The principal purpose of this paper is to report the preparation of cross-linked poloxamer hydrogel spheres in an aqueous two-phase system without the use of organic solvent and additional emulsifier and physicochemical properties related to drug release. Poloxamer 188 was modified with methacryloyl chloride to obtain the polymerizable derivative (macromer). The aqueous solution of the macromer was mixed with dextran/magnesium sulfate aqueous solution to form a water-in-water emulsion system. After polymerizing the macromer in the dispersion phase, nonporous particles with a mean diameter of micron level were prepared. Both the mean diameter and swelling ratio of spheres can be tailored by varying the starting composition of the preparations. The drug release experiments indicate that the release of vitamin B12 entrapped in the spheres follows first-order kinetics.
Chemical Phenomena↗
Nitric oxide and peroxynitrite in postischemic myocardium.
Alterations in the production of nitric oxide (NO.) are a critical factor in the injury that occurs in ischemic and reperfused myocardium; however, controversy remains regarding the alterations in NO. that occur and how these alterations cause tissue injury. As superoxide generation occurs during the early period of reperfusion, the cytotoxic oxidant peroxynitrite (ONOO-) could be formed; however, questions remain regarding ONOO- formation and its role in postischemic injury. Electron paramagnetic resonance spin trapping studies, using the NO. trap Fe(2+)-N-methyl-D-glucamine dithiocarbamate (Fe-MGD), and chemiluminescence studies, using the enhancer luminol, have been performed to measure the magnitude and time course of NO. and ONOO- formation in the normal and postischemic heart. Isolated rat hearts were subjected to control perfusion, or ischemia followed by reperfusion in the presence of Fe-MGD with electron paramagnetic resonance measurements performed on the effluent from these hearts. Whereas only trace signals were present prior to ischemia, prominent NO. adduct signals were seen during the first 2 min of reflow. The reperfusion associated increase in these NO. signals was abolished by nitric oxide synthase inhibition. In hearts perfused with luminol to detect ONOO- formation, a similar marked increase was seen during the first 2 min of reperfusion that was blocked by nitric oxide synthase inhibitors and by superoxide dismutase. Either NG-nitro-L-arginine methyl ester or superoxide dismutase treatment resulted in more than twofold higher recovery of contractile function than in untreated hearts. Immunohistology studies demonstrated that the ONOO(-)-mediated nitration product nitrotyrosine was formed in postischemic hearts, but not in normally perfused controls. Thus, NO. formation is increased during the early period of reperfusion and reacts with superoxide to form ONOO-, which results in protein nitration and myocardial injury.
Animals↗
[Cloning and characterization of a novel human cancer/testis-associated gene].
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Amino Acid Sequence↗
[Arthropod community structures in transgenic Bt cotton fields].
Arthropod community structures were investigated in transgenic Bt cultivars, Bollgard(B) and Chinese cotton 30 (CC30), and common cultivars, control (C) and no control (NC) cotton field in North China in 1998. The results showed that compared with common cultivars, the species richness and the number of total individual of arthropod community in transgenic Bt cultivars field were reduced 2.4-16.3% and 71.0-78.3% respectively, in which dominant species in phytophagous subcommunity varied. The number of individual of predatory and parastic subcommunity were all increased. The similarity coefficient between CC30 and NC was 0.8243, B and NC 0.7320, B and C 0.3380, C and NC 0.3128, CC30 and C 0.2665. The order of diversity and evenness value of these were CC30 (2.3712 and 0.6428), NC (2.3654 and 0.6251), B (2.1364 and 0.5791), and C (1.0877 and 0.2949), their dominant value was 0.8726 (C), 0.3528(B), 0.1178(NC) and 0.1048 (CC30) respectively. It was concluded that different integrated pest management (IPM) strategy should be implemented in transgenic Bt cotton instead of common variety cotton field.
Animals↗
[Advances of peripheral nerve regeneration using nerve guidance channel].
The applications and advances of nerve guidance channel used as peripheral nerve repair and regeneration have been reviewed. There are two main aspects: the design of nerve guidance channel itself, and the creation of regeneration microenvironment in the nerve guidance channel.
Animals↗
Expression of the Recombinant Human Interleukin-11 in Pichia pastoris.
Full length cDNA of human IL-11 was synthesized by DNA synthesizer. An expression plasmid, pGENYk, containing the recombinant DNA fragment, was linearized and transformed into Pichia pastoris. This recombinant gene was highly expressed in this yeast, and the expression product was purified by a three-step chromatography method. Analysis of the purified recombination protein with SDS-PAGE, Western blot and biological activities showed that the activity of the protein was the same as the Neumega expressed in E.coli.
Journal Article↗