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Biomedical subjects

R Wang

Publications and source records attributed to R Wang.

At least 523 records · Page 29Linked to original sources

Induction of protective polyclonal antibodies by immunization with a Plasmodium yoelii circumsporozoite protein multiple antigen peptide vaccine.

Monoclonal Abs against the repeat region of the circumsporozoite protein (CSP) completely protect mice against Plasmodium yoelii (Py), but synthetic peptide and recombinant protein vaccines designed to produce only Abs to the PyCSP repeat region have never been reported to consistently provide protection. This lack of protection in the rodent model system has predicted the poor protection achieved in humans after immunization with synthetic peptide and recombinant protein P. falciparum CSP vaccines and has raised serious questions regarding the capacity for vaccine-induced polyclonal Abs against the CSP to consistently protect humans. We now report immunization studies with a multiple Ag peptide vaccine designed to rely on "universal" T epitopes from tetanus toxin to produce T cell help for induction of protective Abs against the repeat region of the PyCSP. When delivered with a nonionic block co-polymer adjuvant, the vaccine protected 78 to 100% of three inbred strains of mice, and 100% of outbred mice against P. yoelii sporozoite challenge. Protection was associated with Ab titer, and passive transfer of purified IgG from immune mice protected naive recipients. Similar protection was achieved when the peptide was encapsulated in liposomes with lipid A and mixed with aluminum hydroxide. By demonstrating for the first time solid protection against P. yoelii by polyclonal Abs against the CSP, these data provide the rationale for assessment of a similarly constructed and formulated P. falciparum CSP multiple Ag peptide vaccine in humans.

Amino Acid Sequence↗

Ceruloplasmin: an endogenous depolarizing factor in neurons?

The biological effects of ceruloplasmin have been exclusively ascribed to its roles as a copper carrier and an antioxidant. Although neuronal involvement of ceruloplasmin is closely related to aging and certain neuronal disorders, neuronal effects of ceruloplasmin are unknown and the possible modulation of membrane potential and ion channels by ceruloplasmin has not been investigated. In the present study, the membrane electrical properties of neuroblastoma cells in the presence of ceruloplasmin were studied using the patch-clamp technique. Ceruloplasmin induced a rapid and sustained membrane depolarization. This capacity of ceruloplasmin was abolished either when the copper was removed from ceruloplasmin or when ceruloplasmin was heat-inactivated. The depolarizing effect of ceruloplasmin was not due to an enhanced Ca2+ or Na+ influx but it seemed to result from a reduced K+ efflux since ceruloplasmin significantly inhibited a TEA-sensitive delayed rectifier K+ channel. To our knowledge, this is the first report which indicates that ceruloplasmin is an endogenous neuronal depolarizing factor.

Calcium↗

Limited T cell antigen receptor repertoire in tumor-infiltrating lymphocyte and inhibition of experimental lung metastasis of murine melanoma by anti-TCR antibody.

We analyzed the variability of T cell Ag receptor in tumor-infiltrating lymphocytes in primary and metastatic melanomas. Using a very sensitive inverse/double step PCR, we found the preferential V alpha usage of TCR in tumor-infiltrating lymphocytes in which some TCR sequences were homogenous. However, the profile of TCR V alpha expression was different in primary and metastatic melanomas. V alpha 8+, V alpha 2+, V alpha 4+, and V alpha 3+ TCR were the most dominant repertoires in primary melanoma, whereas V alpha 3+ and V alpha 4+ TCR dominated metastatic melanoma. Depletion of V alpha 3 T cells by the injection of tumor-bearing mice with anti-V alpha 3 Ab resulted in protection against experimental lung metastasis, indicating that V alpha 3+ regulatory T cells exist in the tumor site and help metastatic tumor growth.

Amino Acid Sequence↗

Allosteric regulation of the ATP sulfurylase associated GTPase.

ATP sulfurylase catalyzes and chemically links the hydrolysis of GTP and the synthesis of activated sulfate (APS). Like many GTPases, its GTPase activity is allosterically regulated, in this case, by APS-forming reactants and their analogues. Using these activators, we have been able to mimic many of the complexes that form in the native reaction, including an E.AMP intermediate. The effects of each of these complexes on GTP hydrolysis are determined. The results of pre-steady-state and isotope trapping studies demonstrate that the binding of activator and substrate to the enzyme are near equilibrium and that the rate-determining step appears to be scission of the beta, gamma-bond of GTP. These properties of the system allow the energetic consequences of activator binding on the ground- and transition-state complexes to be evaluated. Activation occurs predominantly by transition-state stabilization, resulting in kcat increases. The values for kcat span a 180-fold range and vary with each activator. Km, or ground-state, effects are relatively small, approximately 3-fold, and are uniform throughout the activator series. These studies provide an in-depth view of the energetic interactions between the two active sites at each step of the APS-forming reaction.

Acid Anhydride Hydrolases↗

Dynamics surrounding Cys-34 in native, chemically denatured, and silica-adsorbed bovine serum albumin.

We report the steady-state and time-resolved fluorescence of 6-acryloyl(dimethylamino)naphthalene (acrylodan) covalently attached to Cys-34 in bovine serum albumin (BSA). For this conceptually simple system, complicated fluorescence intensity and anisotropy decay kinetics are observed. The steady-state and time-resolved results demonstrate the presence of an excited-state reaction for the BSA-acrylodan system. Additional analysis shows that dipolar relaxation of the environment surrounding acrylodan within BSA is responsible for most of the observed time-dependent evolution of the emission spectrum. The effects of temperature, chemical denaturation, and protein adsorption to a bare silica substrate are also investigated. These results demonstrate the complexity of the changes within a protein/biorecognition element that affect the signal from a single fluorescent reporter group.

2-Naphthylamine↗

Concerted evolution of mammalian cardiac myosin heavy chain genes.

We have recently determined the complete nucleotide sequences of the cardiac alpha- and beta-myosin heavy chain (MyHC) genes from both human and Syrian hamster. These genomic sequence data were used to study the molecular evolution of the cardiac MyHC genes. Between the alpha- and beta-MyHC genes, multiple gene conversion events were detected by (1) maximum parsimony tree analyses, (2) synonymous substitution analyses, and (3) detection of pairwise identity of intron sequences. Approximately half of the 40 cardiac MyHC exons have undergone concerted evolution through the process of gene conversion with the other half undergoing divergent evolution. Gene conversion occurred more often in exons encoding the alpha-helical myosin rod domain than in the globular head domain, and an apparent directional bias was also observed, with transfer of genetic material occurring more often from beta to alpha.

Animals↗

Allozyme differentiation among nine populations of the corn borer (Ostrinia) in China.

To test the hypothesis of the migration of the corn borer, the allozymes of nine populations of the corn borer (Ostrinia) in China were checked using vertical-slab polyacrylamide gel electrophoresis. Eight loci of six allozymes were analyzed. The mean of the genetic identities among the nine populations calculated from the allele frequencies was 0.99068, much closer than that of other species and geographical populations. The mean (0.97955) of the genetic identities between the XJYN population (Ostrinia nubilalis Hübner, collected from Yining, Xinjiang Autonomous Region) and each of the other eight populations (O. furnacalis Guenée) was significantly smaller than that between the pairs of the eight populations (0.99386; t test, P < 0.01). Although the population XJYN clearly deviates from the other eight populations in the dendrogram, the relationship of the two species of corn borer was very close. It is possible that the speciation of corn borer may have resulted from single-gene substitutions.

Animals↗

Characterization and structural organization of the cardiac beta-myosin heavy chain gene from Syrian hamster.

In order to perform comparative studies of the cardiac myosin heavy chain (MyHC) genes, we determined the sequence of the Syrian hamster beta-MyHC gene and its 5' flanking region. This 33,960 basepair (bp) sequence contains 12,196 bp of the 5' flanking region as well as 21,731 bp of the complete beta-MyHC gene, with its 3' end overlapping with the alpha-MyHC gene. All the exon/intron boundaries were determined and relative to the human beta-MyHC gene, an extra 5' untranslated exon was identified. The isolation and sequencing of the Syrian hamster beta-MyHC gene may further the understanding about the regulation and the evolution of the cardiac MyHC genes.

Amino Acid Sequence↗

Altered calcium homeostasis in tail artery endothelial cells from spontaneously hypertensive rats.

Using the fura-2 fluorescence technique, the hypothesis that calcium homeostasis may be altered in vascular endothelial cells of spontaneously hypertensive rats (SHR) was examined. Endothelial cells (EC) were isolated from rat tail arteries and subcultured for up to three passages. The resting intracellular calcium ion concentration ([Ca2+]i) in EC from tail arteries was found to be significantly lower in SHR than that in normotensive Wistar-Kyoto (WKY) rats. Bradykinin and endothelin induced a lesser increase in [Ca2+]i in both the peak increase and the total amount of calcium increase during a defined period of time in tail artery EC from SHR, compared with the respective EC from WKY rats. However, there was no significant difference in angiotensin II induced increase in [Ca2+]i in tail artery EC between SHR and WKY rats. It is suggested that a lower resting [Ca2+]i and a selectively impaired stimulation-induced increase in [Ca2+]i in EC may contribute to the altered endothelium function in spontaneously hypertensive rats.

Angiotensin II↗

Effect of continuous arteriovenous hemofiltration combined with systemic vasopressor therapy on depressed left ventricular contractility and tissue oxygen delivery in canine Escherichia coli sepsis.

BACKGROUND: In a previous study, we showed that continuous arteriovenous hemofiltration (CAVH) reversed the depression in left ventricular (LV) contractility in canine Escherichia coli sepsis by the removal of a circulating substance the molecular weight of which is less than 30,000. Despite the normalization of LV contractility, however, we were unable to demonstrate an improvement in systemic arterial blood pressure (BP), presumably because the mechanisms underlying the depression in LV contractility and the decrease in BP are different in sepsis. In the current study, we examined the effect of combined treatment with CAVH and the alpha-adrenergic agonist phenylephrine on LV mechanics and tissue oxygen delivery in our canine E. coli model. METHODS: Measurements were obtained at baseline (condition B), after 4 h of sepsis (condition S), and after 2 h of CAVH and phenylephrine (condition P) (total of 6 h of sepsis). During P, phenylephrine was infused to restore BP to that found at baseline. The slope of the end-systolic pressure-dimension relation was used as the index of LV contractility; LV anterior-posterior dimensions were measured by sonomicrometry. RESULTS: During combined CAVH and phenylephrine treatment, the decrease in the slope of the end-systolic pressure-dimension relation otherwise observed at S was reversed. The slope (mean +/- SD) was 57.5 +/- 32 mmHg/mm at B versus 22.2 +/- 8 mmHg/mm at S (P < 0.05, B vs. S) versus 62 +/- 37 mmHg at P (P < 0.05 S vs. P) (analysis of variance). Mean BP was restored to that found at B (123 +/- 19 mmHg versus 82 +/- 14 mmHg (P < 0.05 B vs. S) versus 116 +/- 27 mmHg (P < 0.05 S vs. P). Combination treatment with CAVH and phenylephrine also improved stroke volume (39.3 +/- 13.5 versus 32 +/- 8 versus 44 +/- 12 ml) and tissue oxygen delivery during P compared with results obtained when phenylephrine was given alone. CONCLUSIONS: Our study offers a rationale for the combined use of phenylephrine and CAVH in the reversal of cardiac depression and hypotension in sepsis.

Animals↗

A simple competitive account of some response properties of visual neurons in area MSTd.

A simple and biologically plausible model is proposed to simulate the optic flow computation taking place in the dorsal part of medial superior temporal (MSTd) area of the visual cortex in the primates' brain. The model is a neural network composed of competitive learning layers. The input layer of the network simulates the neurons in the middle temporal (MT) area that selectively respond to the visual stimuli of the input motion patterns with different local velocities. The output layer of the network simulates the MSTd neurons that selectively respond to different types of optic flow motion patterns including planar, circular, radial, and spiral motions. Simulation results obtained from this model show that the behaviors of the output nodes of the network resemble very closely the known responsive properties of the MSTd neurons found neurophysiologically, such as the existence of three types of MSTd neurons that respond, respectively, to one, two, or three types of the input motion patterns with different position dependences, and the continuum of response selectivity formed by the three types of neurons.

Animals↗

Ballistics and visual targeting in flea-beetles (Alticinae)

The kinematics of jumping was measured in seven species of flea-beetle (Alticinae). The accuracy of two species during targeted jumping was also investigated. Take-off accelerations ranged from 15 to 270 times gravity. Rotational energy accounted for 4&shy;21 % of the total translational energy. Two species were able to control jump direction and landing. When presented with a high-contrast optical grid, Chalcoides aurata exhibited two alternative jump modes. In mode 1 or wingless jumping, the body rotated continuously, the insect rarely landed on its feet and no discrimination was shown between landing on the black or white stripes of the grid. In mode 2 jumping, recruitment of the wings eliminated rotation and virtually ensured a feet-first landing; there was also a significant preference for jumping towards the black stripes. Aphthona atrocaerulea could alter take-off angle in order to strike targets at inclinations of 0&shy;90 &deg; to the horizontal. Targets consisting of a white illuminated cross on a black background were struck with equal accuracy, regardless of distance (within the normal jumping range). The beetle aimed specifically for the centre of the target and not for the high-contrast boundary. The distribution of hits about the target centre was radially symmetrical. Although take-off was wingless, rotation could be abolished in mid jump, within 10 ms, by extending the wings. This virtually guaranteed a feet-first landing. Targeting accuracy is discussed in the context of biomechanical steering mechanisms and visual control.

Journal Article↗

[Simplified enzyme-linked immunoadsorbent assays for myelin basic protein and antibodies to myelin basic protein].

Synchronous quantitative determination using simplified enzyme-linked immuno adsorbent assay has been developed for myelin basic protein (MBP) and antibodies to myelin basic protein (Anti-MBP). Antisera were prepared by immunizing rabbits with purified MBP from human white matter. Antibodies to MBP was conjugated with horseradish peroxidase (HRP) by using modified periodate oxidation method. Minimum detection amounts of MBP and Anti-MBP are 0.25 ng/ml and 0.20 ng/ml respectively. The activities of Anti-MBP-HRP conjugates are stable (stored at -30 degrees C) for at least 2 years. The detection procedure can be accomplished within 24 hours.

Animals↗