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Biomedical subjects

R Wang

Publications and source records attributed to R Wang.

At least 757 records · Page 42Linked to original sources
PubMedDate not supplied

Immunogenicity of Plasmodium falciparum circumsporozoite protein multiple antigen peptide vaccine formulated with different adjuvants.

Only low antibody levels were obtained from vaccinating human volunteers with single-chain peptide from the Plasmodium falciparum circumsporozoite protein (PfCSP). This resulted in modest protection against sporozoite challenge. In addition, HLA restriction limits the probability of synthesis of a vaccine effective for a diverse population. We report immunization studies with a multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell epitope from the central repeat region of the PfCSP in combination with a universal T-cell epitope, the P2P30 portion of tetanus toxin. This MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice when used with various safe and nontoxic adjuvants. When this MAP vaccine was encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and given three times at 4-week intervals, the resultant antibody prevented 100% of sporozoites from invading and developing into liver stage infection. This high degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes, lipid A and aluminum hydroxide provides the foundation for consideration of human trials with this formulation.

Adjuvants, Immunologic↗
PubMedDate not supplied

Applications of controlled-flow laser-polarized xenon gas to porous and granular media study.

We report initial NMR studies of continuous flow laser-polarized xenon gas, both in unrestricted tubing, and in a model porous media. The study uses Pulsed Gradient Spin Echo-based techniques in the gas-phase, with the aim of obtaining more sophisticated information than just translational self-diffusion coefficients. Pulsed Gradient Echo studies of continuous flow laser-polarized xenon gas in unrestricted tubing indicate clear diffraction minima resulting from a wide distribution of velocities in the flow field. The maximum velocity experienced in the flow can be calculated from this minimum, and is seen to agree with the information from the complete velocity spectrum, or motion propagator, as well as previously published images. The susceptibility of gas flows to parameters such as gas mixture content, and hence viscosity, are observed in experiments aimed at identifying clear structural features from echo attenuation plots of gas flow in porous media. Gas-phase NMR scattering, or position correlation flow-diffraction, previously clearly seen in the echo attenuation data from laser-polarized xenon flowing through a 2 mm glass bead pack is not so clear in experiments using a different gas mixture. A propagator analysis shows most gas in the sample remains close to static, while a small portion moves through a presumably near-unimpeded path at high velocities.

Diffusion↗
PubMedDate not supplied

Preparation and characterization of biologically active 6'-O-(6-aminocaproyl)-4'-O-monophosphoryl lipid A and its conjugated derivative.

N-tert-butyloxycarbonyl (t-Boc) protected 6-aminocaproic (Cap) anhydride was reacted with unprotected hexaacyl-4'-O-monophosphoryl lipid A (MLA) obtained from the lipopolysaccharide of Escherichia coli J5 to yield t-Boc-Cap-MLA. After a column purification step, the t-Boc group was removed by incubating the sample at low temperature in the presence of acid to yield Cap-MLA. This product was analyzed by californium plasma desorption mass spectrometry (PDMS). Purified t-Boc-Cap-MLA was further fractionated by reverse-phase high-performance liquid chromatography as its methyl ester and characterized by laser desorption mass spectrometry, PDMS, and proton nuclear magnetic resonance spectroscopy. These analyses revealed that the Cap group was selectively introduced into the 6'-position of MLA. To demonstrate that Cap-MLA can be conjugated to other compounds, it was reacted with biotin-Cap N-hydroxysuccinimide ester to yield biotin-(Cap)2-MLA. Analysis of this product by PDMS confirmed its expected molecular weight of 2171 and showed the presence of fragments containing the biotin and Cap groups. Monoclonal antibodies and streptavidin were used to show the presence of both lipid A and biotin in this conjugated product. These two novel lipid A derivatives were then tested for their bioactivities. Although both Cap-MLA and biotin-(Cap)2-MLA showed mitogenic activity using murine splenocytes, they were about 4-8 times less active than MLA at 20 micrograms/mL or less and only one-half as active at 100 micrograms/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

How does consensus scoring work for virtual library screening? An idealized computer experiment.

It has been reported recently that consensus scoring, which combines multiple scoring functions in binding affinity estimation, leads to higher hit-rates in virtual library screening studies. This method seems quite independent to the target receptor, the docking program, or even the scoring functions under investigation. Here we present an idealized computer experiment to explore how consensus scoring works. A hypothetical set of 5000 compounds is used to represent a chemical library under screening. The binding affinities of all its member compounds are assigned by mimicking a real situation. Based on the assumption that the error of a scoring function is a random number in a normal distribution, the predicted binding affinities were generated by adding such a random number to the "observed" binding affinities. The relationship between the hit-rates and the number of scoring functions employed in scoring was then investigated. The performance of several typical ranking strategies for a consensus scoring procedure was also explored. Our results demonstrate that consensus scoring outperforms any single scoring for a simple statistical reason: the mean value of repeated samplings tends to be closer to the true value. Our results also suggest that a moderate number of scoring functions, three or four, are sufficient for the purpose of consensus scoring. As for the ranking strategy, both the rank-by-number and the rank-by-rank strategy work more effectively than the rank-by-vote strategy.

Computer Simulation↗
PubMedDate not supplied

RASSE: a new method for structure-based drug design.

A novel method, RASSE, has been developed to suggest reasonable structures which can fit well to the binding sites of receptors. Molecules are generated by an iterative growing procedure in which atoms are added to existing fragments. Potential ligands are then picked out by special scoring rules. This atomgrowing based method is characterized by combinatorial searching of atom types and conformations. To some extent, it is the computer simulation of combinatorial chemistry. This method has been applied to the design of inhibitors for E. coli dihydrofolate reductase and human phospholipase A2. The results demonstrate that this program is capable of generating reasonable structures, thus proving its power in drug design.

Binding Sites↗
PubMedDate not supplied

A protein from human placental nuclei binds preferentially to 5-methylcytosine-rich DNA.

The methylation of vertebrate DNA at the 5-position of approximately 3-10% of its cytosine residues occurs in a sequence-specific and tissue-specific manner and has been implicated in the control of transcription. How these differences are established and how they mediate the initiation or maintenance of transcription are unknown. DNA methylation might also have other roles, such as modulating DNA replication, transposition, DNA repair or chromosome configuration. These other roles suggested for DNA methylation would be consistent with the finding that tissue-specific differences in methylation of certain gene regions, highly repeated satellite DNA sequences and whole genomes often do not correlate with transcriptional activity. For DNA methylation to modulate the expression, maintenance or duplication of chromosomes, there should be effector macromolecules, presumably proteins, which specifically recognize 5-methylcytosine (m5C) residues in DNA. We describe here the first identification of a mammalian protein that binds preferentially to m5C-rich DNA sequences.

Binding, Competitive↗
PubMedDate not supplied

Near-field mapping of the emission distribution in semiconductor microdiscs.

We have used a scanning near-field optical microscope to study the fluorescent light distribution in the near- and far-fields with two types of microdiscs, InGaP and GaN, fabricated in our laboratory. The InGaP microdisc has a radius of 2.5-5.0 microm, a thickness of 0.15-0.2 microm and a circular shape and the GaN disc has a radius of 5-8 microm with a thickness of 0.5-2 microm. Spontaneous emission enhancement in these microdiscs has been observed with emitting wavelengths of 650 and 550 nm respectively In both types of microdisc, the whispering-gallery mode (WCM) has been observed on the top surface using near-field optical and far-field microscopic methods. However, due to the different disc structures and optical confinements, the light distributions of the type types of disc are quite different. In the case of the InGaP disc, WGM is the dominant mode with a mixture of other modes. Interference-like ring intensities have been observed both inside the disc surface and outside, with a period ratio of 1:2. In addition, the propagating waves emitted from the side of the disc have been collected for the first time by using near-field optical microscopy. A theoretical calculation based on the theory of optical modes in microdisc lasers confirmed this observation. It also predicted the behaviour of the electric field distribution (transverse electric) inside and outside the disc, as well as the period of the wave propagation. In contrast, the near-field mapping of the GaN fluorescence showed not only a ring-like emission intensity along the circumference of the disc, an indication of WGM, but also an even intensity distribution inside the disc. This can be explained as the combination of the WGM with the Fabry-Perot mode of multi-reflection between the GaN layer and the substrate. The results also demonstrate the potential application of near-field optics to explore the light emission mode of a microdisc on a nanometre scale.

Journal Article↗
PubMedDate not supplied

Hypertrophic scar tissues and fibroblasts produce more transforming growth factor-beta1 mRNA and protein than normal skin and cells.

Transforming growth factor-beta1 is a well-known fibrogenic cytokine produced by many types of cells including dermal fibroblasts. To investigate whether this fibrogenic cytokine is involved in development of hypertrophic scar, transforming growth factor-beta1 gene expression was evaluated in small skin samples. Because a sufficient quantity of normal skin from patients with hypertrophic scar is not readily available, a reverse transcription-polymerase chain reaction technique was used. Quantitation of gene expression by reverse transcription-polymerase chain reaction is difficult partly due to the lack of suitable complementary RNA standards. We have established a convenient, reliable procedure to construct an internal standard for transforming growth factor-beta1 starting with a gene specific polymerase chain reaction product. After digestion of the polymerase chain reaction product with endonuclease, a small piece of cDNA from human procollagen alpha1(I) cDNA with compatible ends was inserted into the polymerase chain reaction-DNA fragment. The recombinant cDNA was re-amplified by polymerase chain reaction and subcloned into a plasmid containing bacteriophage T7 and T3 promoters. Complementary RNA was prepared from the recombinant plasmid and amplified by reverse transcription-polymerase chain reaction together with the tissue or cellular RNA. After amplification, the products were electrophoresed in an agarose gel containing ethidium bromide. The bands for internal standard and transforming growth factor-beta1 mRNA were scanned, digitized, and plotted against the amount of internal standard complementary RNA added in the reverse transcription-polymerase chain reaction. The number of mRNA molecules/cell was calculated. We examined the transforming growth factor-beta1 mRNA in hypertrophic scar tissue and in normal skin and found that hypertrophic scar tissues expressed five-fold more transforming growth factor-beta1 mRNA than normal skin per unit of wet weight. We used this procedure to quantitate transforming growth factor-beta1 mRNA expression in 5 pairs of fibroblast cultures derived from hypertrophic scar and normal skin. The results showed that hypertrophic scar fibroblast cultures contain significantly more molecules of mRNA for transforming growth factor-beta1 than normal cells (116 +/- 6 vs. 97 +/- 7, p = 0.017, n = 5). These results were supported by Northern analysis for transforming growth factor-beta1 mRNA in the cells and enzyme-linked immunosorbent assay for TGF-beta1 protein in fibroblast-conditioned medium. In conclusion, hypertrophic scar tissue and fibroblasts produce more mRNA and protein for transforming growth factor-beta1, which may be important in hypertrophic scar formation. The construction of the gene specific internal standard for reverse transcription-polymerase chain reaction is a simple and reliable procedure useful to quantitate gene expression in a small amount of tissue or number of cells.

Biopsy, Needle↗
PubMedDate not supplied

Biological monitoring of dichloropropene: air concentrations, urinary metabolite, and renal enzyme excretion.

Fifteen applicators of dichloropropene (DCP) were studied for personal air exposure to DCP, excretion of the metabolite of DCP (3CNAC), and excretion of the renal tubular enzyme, N-acetyl glucosaminidase (NAG). Each was studied for four 6-8 h consecutive intervals following baseline determinations of 3CNAC and NAG excretion. In accord with pilot data, 24-h urinary excretion of 3CNAC (mg) correlated well with exposure product for DCP (min exposed.mg/m3), r = 0.854, p less than .001. A more precise correlation of the air exposure product with urinary excretion of 3CNAC was discerned by using the morning urine after the previous day of exposure (micrograms/mg of creatinine), r = 0.914, p less than .001. Four workers had clinically elevated activity of NAG (greater than 4 mU/mg creatinine) in any of their urine collections after baseline. Nine workers showed greater than 25% increases in NAG excretion when compared to baseline. Dichloropropene air exposure products of greater than 700 mg.min/m3 or excretion of greater than 1.5 mg 3CNAC/d distinguished abnormally high daily excretion of NAG. These data demonstrate a firm positive relationship between air exposure and internal exposure, and a possible subclinical nephrotoxic effect in DCP workers.

Acetylcysteine↗
PubMedDate not supplied

Preference for male children and contraceptive use in Taiwan.

Taiwan has an active family-planning program. Yet the preference for sons is deeply ingrained in the Chinese culture and may discourage women from limiting their family size if they feel they have too few sons. In this study, research problems concerned the relationships between women's stated preferences for the sex of their children, their perceptions of their in-laws' preferences for the number and sex of their children, and their use of birth control and choice of birth control methods. It was found that few women verbalized a preference for the sex of children, but the number of boys already in the family was related to the reliability of contraceptive method used later and to the willingness to consider abortion if pregnancy occurred. The desired number and occurrence of additional children related to women's perceptions of their in-laws' preferences for boys. The perception of in-laws' preferences for girls either related negatively or was not significant.

Adult↗
PubMedDate not supplied

Patterns of contraceptive use among urban women in Taiwan.

Patterns of contraceptive use among married urban women in Taiwan were investigated. A convenience sample of 150 women attending health clinics for reasons other than contraceptive care were interviewed about their contraceptive use. The most prevalent contraceptive method used by these women was the intrauterine device, followed by the condom and birth-control pills. Participants had used only one or two contraceptive methods throughout their contraceptive careers, and many stated they were satisfied with their current method. Many participants were able to name the methods of birth control promoted by the Taiwan family-planning promotion program. Knowledge of alternative methods did not significantly relate to current method in use or to desire to change methods.

Adult↗
PubMedDate not supplied

A new phenolic glycoside from the roots of Paeonia veitchii.

From the roots of Paeonia veitchii Lynch., a new phenolic glycoside, 2-O-[alpha-L-arabinopyranosyl-(1 --> 6)-beta-D-glucopyranoside]-benzaldehyde (1) was isolated together with seven known phenolic compounds. Their structures were elucidated by spectroscopic method.

Benzaldehydes↗
PubMedDate not supplied

Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study.

An 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study was conducted to evaluate the antihypertensive efficacy of candesartan vs. losartan in 654 hypertensive patients with a diastolic blood pressure between 95 and 114 mm Hg from 72 sites throughout the U.S. Eligible patients were randomized to candesartan cilexetil 16 mg once daily, or losartan 50 mg once daily. Two weeks following randomization, patients doubled the respective doses of their angiotensin receptor blockers for an additional 6 weeks. At week 8, candesartan cilexetil lowered trough systolic/diastolic blood pressure by a significantly greater amount than did losartan (13.3/10.9 mm Hg with candesartan cilexetil vs. 9.8/8.7 mm Hg with losartan; p less than 0.001). At the same period, candesartan cilexetil also lowered peak blood pressure by a significantly greater amount than did losartan (15.2 to 11.6 mm Hg with candesartan cilexetil vs. 12.6 to 10.1 mm Hg with losartan; p less than 0.05). There were statistically significantly (p less than 0.05) higher proportions of responders and controlled patients in the candesartan cilexetil group (62.4% and 56.0%, respectively) than in the losartan group (54.0% and 46.9%, respectively). Both treatment regimens were well tolerated; 1.8% in the candesartan cilexetil group and 1.6% in the losartan group withdrew because of adverse events. In conclusion, this forced-titration study confirms that candesartan cilexetil is more effective than losartan in lowering blood pressure when both are administered once daily at maximum doses. Both drugs were well tolerated. (c)2001 by Le Jacq.

Adult↗
PubMedDate not supplied

Erythrocyte aldehyde dehydrogenase and disulfiram-like side effects of hypoglycemics and antianginals.

Disulfiram-like responses to various drug therapies are caused by elevated ethnol-derived blood acetaldehyde concentrations resulting from drug-induced inhibition of aldehyde dehydrogenase enzymes. We have found that the nitrate ester antianginal drugs, isosorbide dinitrate and nitroglycerin, are potent inhibitors of human erythrocyte aldehyde dehydrogenase. To further characterize this drug-induced enzyme inhibition, erythrocyte aldehyde dehydrogenase activities were measured in patients undergoing therapy with nitrate ester antianginals (isosorbide dinitrate and nitroglycerin) and sulfonylurea hypoglycemics (chlorpropamide and tolazamide). The erythrocyte enzyme was decreased by approximately 25% in sulfonylurea-treated patients, whereas in the nitrate ester-treated patients, an 88% inhibition was observed. The minimal enzyme inhibition in the sulfonylurea-treated group was unexpected because these therapies have well-documented disulfiram-like side effects. This weak inhibition contrasted with the severe inhibition observed in the nitrate ester-treated group where the disulfiram-like side effects are not considered a serious clinical problem. This apparent anomaly was attributed to differences in inhibition of the erythrocyte and liver aldehyde dehydrogenase by the parent drugs and their hepatic metabolites.

Aldehyde Dehydrogenase↗
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Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels.

BACKGROUND: Total parenteral nutrition (TPN) prevents progressive malnutrition but fails to maintain intestinal gut-associated lymphoid tissue (GALT) or established respiratory antiviral or antibacterial mucosal immunity. Our previous work demonstrated that decreases in intestinal immunoglobulin A (IgA) were associated with decreases in Th2-type IgA-stimulating cytokines, interleukin (IL)-4 and IL-10. Because glutamine supplementation of TPN partially preserves respiratory defenses and normalizes GALT, we investigated the ability of parenteral glutamine to normalize respiratory and intestinal IgA levels and measured Th2 cytokines in intestinal homogenates. METHODS: Animals were cannulated and randomly assigned to receive chow (n = 17), TPN (n = 18), or an isonitrogenous, isocaloric TPN solution formulated by removing the appropriate amount of amino acids and replacing them with 2% glutamine (n = 18) for 5 days. Respiratory tract and intestinal washings were obtained for IgA and the intestine homogenized and analyzed for IL-4 and IL-10. RESULTS: TPN decreased intestinal and respiratory IgA in association with decreases in intestinal IL-4 and IL-10 compared with chow-fed animals. Glutamine significantly improved respiratory and intestinal IgA levels, significantly improved IL-4 compared with TPN animals, and maintained IL-10 levels midway between chow-fed and TPN animals. CONCLUSIONS: Glutamine-enriched TPN preserved both extraintestinal and intestinal IgA levels and had a normalizing effect on Th2-type IgA-stimulating cytokines.

Animals↗
PubMedDate not supplied

Virginiamycin metabolism in cattle rumen fluid.

The antibiotic virginiamycin (VM) was extensively metabolized in cattle rumen fluid in vitro. The antimicrobial activity of VM decreased rapidly with an initial half-life of approximately 8 hr. In contrast, in buffer at near neutral pH, VM maintained its full activity for at least 24 hr. Four metabolites were isolated and identified using a combination of spectral techniques including FAB MS-MS, LC-MS, and 500 MHz NMR. The metabolites were all derived from reduction of the major component of virginiamycin, factor M. The minor component, factor S, was not metabolized in cattle rumen fluid. The metabolic pathways involved included C = C and C = O reduction as well as dehydroxylation. All metabolites were found to have less antimicrobial activity than the parent factor M. In addition to the metabolites, two factor M decomposition products were isolated after incubation of VM in buffer alone. These two products resulted from the dehydration of factor M and were shown to interconvert at room temperature.

Animals↗