Dietary lutein and zeaxanthin: authors' response.
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Diet↗
Biomedical subjects
H Vu
Publications and source records attributed to H Vu.
How to assess the prevalence of trachoma.
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Child↗
On the role of the starved codon and the takeoff site in ribosome bypassing in Escherichia coli.
Translating ribosomes can skip over stretches of messenger RNA and resume protein chain elongation after a "bypassed" region. We have previously shown that limitation for isoleucyl-tRNA can initiate a ribosome bypass when an AUA codon is in the ribosomal A-site. We have now generalized this effect to other "hungry" codons calling for four different limiting aminoacyl-tRNA species, suggesting that a pause at any A-site will have this effect. We have assessed bypassing in a large family of reporters with nearly every different triplet in the "takeoff site", i.e. the P-site on the 5' side of the hungry codon, and an identical "landing site" codon 16 nucleotides downstream. The different takeoff sites vary over a factor of 50 in bypassing proficiency. At least part of this variation appears to reflect stability of the codon Colon, two colons anticodon interaction at the takeoff site, as indicated by the following: (a) the bypassing proficiency of different tRNAs shows a rough correlation with the frequency of A Colon, two colons U as opposed to G Colon, two colons C pairs in the codon Colon, two colons anticodon association; (b) specific tRNAs bypass more frequently from codons ending in U than from their synonym ending in C; (c) an arginine tRNA with Inosine in the wobble position which reads CGU, CGC, and CGA bypasses much more frequently from the last codon than the first two synonyms.
Amino Acid Sequence↗
Recombinant prostate specific antigen inhibits angiogenesis in vitro and in vivo.
BACKGROUND: Prostate specific antigen (PSA) is a kallikrein family member with serine protease activity commonly used as a diagnostic marker for prostate cancer. We recently described anti-angiogenic properties of PSA [Fortier et al.: JNCI 91:1635-1640]. METHODS: Two forms of PSA were cloned and expressed in Pichia pastoris: one, an intact PSA with an N-terminus of IVGGVS em leader; the second, an N-1 PSA variant. The recombinant proteins were tested for serine protease activity and for anti-angiogenic activity in vitro and in vivo. RESULTS: The rate of substrate hydrolysis by the intact recombinant PSA was similar to that of PSA isolated and purified from human seminal plasma. In contrast, the N-1 PSA variant lacked serine protease activity. In an endothelial cell migration assay, the concentration that resulted in 50% inhibition (IC(50)) was: 0.5 microM for native PSA, 0.5 microM for intact recombinant protein, and 0.1 microM for the N-1 variant PSA. Both the intact recombinant and the N-1 recombinant PSA inhibited angiogenesis in vivo. CONCLUSIONS: Purified recombinant PSA inhibits angiogenesis, proving the concept that PSA is an anti-angiogenic, and serine protease activity, as determined by synthetic substrate hydrolysis, is distinct from the anti-angiogenic properties of PSA.
Angiogenesis Inhibitors↗
Reduced pulmonary function and its associations in type 2 diabetes: the Fremantle Diabetes Study.
To determine whether diabetes is associated with reduced lung function, we studied 421 Anglo-Celt/European subjects, representing 20.5% of all patients with type 2 diabetes identified in an urban Australian catchment area of 120097 people. In addition to collection of detailed demographic and diabetes-specific data, spirometry was performed and forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC) and peak expiratory flow (PEF) measured. When expressed as a percentage of those predicted (%pred) for age, sex and height, the means of all spirometric measures were reduced by > or =9.5%. After controlling for smoking, age and gender in a linear regression model, HbA(1c) was not associated with any measure of lung function (P>0.13) but diabetes duration was significantly associated with FEV1(%pred) and PEF(%pred) (P< or =0.04) and had borderline associations with FVC(%pred) and VC(%pred) (P< or =0.064). In separate analyses controlling for smoking alone, age, body mass index (BMI), coronary heart disease (CHD) and retinopathy were independently and inversely associated with FVC(%pred), FEV1(%pred) and VC(%pred) (P<0.05). In sub-group analyses, these three spirometric measures were associated with BMI, CHD and diabetes duration in males, and age and BMI in females. Pulmonary function is reduced in type 2 diabetes. Diabetes duration seems a more important influence than glycaemic control, but obesity and vascular disease may also contribute.
Adult↗
The influence of global discourse on lexical ambiguity resolution.
The influence of global discourse on the resolution of lexical ambiguity was examined in a series of naming experiments. Two-sentence passages were constructed to bias either the dominant or the subordinate meaning of a homonym that was embedded in a locally ambiguous sentence. The results provided evidence for the immediate (0-msec interstimulus interval) resolution of lexical ambiguity and were subsequently replicated in Experiment 2, in which an 80-msec stimulus onset asynchrony exposure duration was employed for the homonyms. Strong dominant and subordinate biased discourse contexts activated only the contextually appropriate sense of a homonym. In Experiment 3, each sentence of the discourse was presented in isolation. The pattern of activation obtained in Experiments 1 and 2 was found to be contingent on the integration of the two sentences to construct an overall global discourse representation of the text. The results support a context-sensitive model of lexical ambiguity resolution.
Cognition↗
Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations.
BACKGROUND: Acylation stimulating protein (ASP) is a potent stimulator of TG synthesis in human adipocytes. DESIGN: In the present study, we have analysed plasma ASP and adipsin levels and their relationships to plasma lipids in non-obese and obese groups. RESULTS: The results show that the frequency distribution of ASP is skewed but that of adipsin is normal in both groups. In the non-obese population, the mean levels of plasma ASP and adipsin were 20.2 nmol L-1 (median) and 66.6 +/- 19 nmol L-1 (mean) respectively. No difference was observed between men and women for each of the parameters. In the obese population, the median plasma ASP was increased by 246% (69.9 nmol L-1) and adipsin by 31% (87.0 +/- 22.7 nmol L-1) above that of the control group. Although the levels for men and women were not statistically different for adipsin, the median ASP plasma concentration was 1.9-fold higher in obese women than in obese men (71.8 nmol L-1 vs. 37.6 nmol L-1, P < 0.05). Best subset regression analysis provided a model with variables that best predict plasma ASP [r2 = 0.160, P < 0.008 for body mass index (BMI), P < 0.05 for triacylglycerol (TG), P < 0.03 for free fatty acid (FFA)] and plasma adipsin (r2 = 0.057, P < 0.017 for BMI) in a non-obese population. In obese subjects, the model was different for plasma ASP (P = NS for any of the variables) and plasma adipsin (r2 = 0.356, P < 0.008 for FFA, P < 0.0002 for BMI, P < 0.02 for age). There was no correlation between ASP and adipsin in either the non-obese or the obese group. CONCLUSION: The present data suggest involvement of the ASP/adipsin pathway in the pathogenesis of obesity.
Adult↗
Strength of discourse context as a determinant of the subordinate bias effect.
Two experiments examined the influence of strength of discourse bias on lexical ambiguity resolution. Short passages were constructed to bias polarized ambiguous words (homonymous) strongly or weakly toward the dominant or subordinate meanings. Using a self-paced reading task in Experiment 1, it was demonstrated that in strongly biased discourse, reading times for homonyms in dominant discourse did not differ from those in subordinate discourse. However, when the discourse was weakly biased, homonyms were read faster in dominant discourse than in subordinate discourse. Experiment 2 combined the reading paradigm with a naming task in order to provide an assessment of specific word-meaning activation. Reading times on ambiguous words replicated the results of Experiment 1. In addition, naming latencies for probe words revealed that only the contextually appropriate sense of a homonym was activated in strongly biased discourse. In contrast, both contextually appropriate and inappropriate senses were activated following a weakly biased subordinate discourse, whereas only the dominant sense was activated following weakly biased dominant discourse. The results demonstrate (1) an immediate influence of prior discourse information on lexical processing; and (2) that the strength of discourse constraints can play a governing role in lexical ambiguity resolution. The results were interpreted within the framework of a context-sensitive model of lexical ambiguity resolution.
Humans↗
Comparative performance of the RapID Yeast Plus System and the API 20C AUX Clinical Yeast System.
The performance of the RapID Yeast Plus System (Innovative Diagnostic Systems, Norcross, Ga.), a 4-h micropanel using single-substrate enzymatic test reactions, was compared with that of the API 20C AUX Clinical Yeast System (bioMerieux Vitek, Hazelwood, Mo.), a 48- to 72-h carbohydrate assimilation panel. Two hundred twenty-five yeasts, yeast-like fungi, and algae, comprising 28 species and including 30 isolates of Cryptococcus neoformans, an important pathogen not tested in appreciable numbers in other comparisons, were tested by both methods. On initial testing, 196 (87.1%) and 215 (95.6%) isolates were correctly identified by the RapID and API systems, respectively. Upon repeat testing, the number of correctly identified isolates increased to 220 (97.8%) for the RapID system and 223 (99.1%) for the API system. Reducing the turbidity of the test inoculum to that of a no. 3 McFarland turbidity standard, which is below that recommended by the manufacturer, resulted in the correct identification of most of the isolates initially misidentified by the RapID system, including 10 of 30 C. neoformans isolates. Concordance between the RapID and API results after repeat testing was 97.3%.
Fungi↗
Strength of context does modulate the subordinate bias effect: a reply to Binder and Rayner.
Using a self-paced reading task, Kellas, Martin, Yehling, Herman, and Vu (1995) demonstrated that strength of context can modulate the effects of meaning frequency. Binder and Rayner (1998) initially replicated the results, using eye-tracking methodology. On further examination of the stimuli, Binder and Rayner eliminated 43% of the stimulus set and found that context strength failed to modulate meaning frequency. Binder and Rayner's initial replication of Kellas et al. and the convergence of results between their two main experiments established the validity of self-paced reading as a measure of on-line reading, when compared with eye-tracking methodology. However, their central conclusion, that context strength cannot modulate the subordinate bias effect, is open to question. In this commentary, we examine the criteria adopted to exclude items from our homonym set and discuss the issue of local versus published norms. We also discuss the issue of context strength, as related to the specific rating procedures employed. Finally, we conclude that strong context can, in fact, eliminate the subordinate bias effect and that the context-sensitive model can more fully account for the available data on lexical ambiguity resolution.
Cognition↗
Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor.
A cDNA encoding a thyrotropin-releasing hormone (TRH) receptor expressed in the pituitary was previously cloned (De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) Biochem. J. 284, 891-899; De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) J. Biol. Chem. 267, 25703-25708; Duthie, S. M., Taylor, P. L., Anderson, J., Cook, J., and Eidne, K. A. (1993) Mol. Cell Endocrinol. 95, R11-R15). We now describe the isolation of a rat cDNA encoding a novel subtype of TRH receptor (termed TRHR2) displaying an overall homology of 50% to the pituitary TRH receptor. Introduction of TRHR2 cDNA in HEK-293 cells resulted in expression of high affinity TRH binding with a different pharmacological profile than the pituitary TRH receptor. De novo expressed receptors were functional and resulted in stimulation of calcium transient as assessed by fluorometric imaging plate reader analysis. The message for TRHR2 was exclusive to central nervous system tissues as judged by Northern blot analysis. Studies of the expression of TRHR-2 message by in situ hybridization revealed a pattern of expression remarkably distinct (present in spinothalamic tract, spinal cord dorsal horn) from that of the pituitary TRH receptor (present in hypothalamus, and ventral horn of the spinal cord, anterior pituitary). Therefore, we have identified a novel, pharmacologically distinct receptor for thyrotropin-releasing hormone that appears to be more restricted to the central nervous system particularly to the sensory neurons of spinothalamic tract and spinal cord dorsal horn, which may account for the sensory antinociceptive actions of TRH.
Amino Acid Sequence↗
The superoxide synthases of rose cells . Comparison Of assays
In an effort to identify the enzymatic mechanism responsible for the synthesis of reactive oxygen species produced during the hypersensitive response, preparations of rose (Rosa damascena) cell plasma membranes, partially solubilized plasma membrane protein, and cytosol were assayed for the NADH- and NADPH-dependent synthesis of superoxide using assays for the reduction of cytochrome c (Cyt c), assays for the reduction of nitroblue tetrazolium, and assays for the chemiluminescence of N,N'-dimethyl-9,9'-biacridium dinitrate (lucigenin). Each assay ascribed the highest activity to a different preparation: the Cyt c assay to cytosol, the nitroblue tetrazolium assay to plasma membrane, and the lucigenin assay to the partially solubilized plasma membrane protein (with NADH). This suggests that no two assays measure the same set of enzymes and that none of the assays is suitable for comparisons of superoxide synthesis among different cell fractions. With the plasma membrane preparation, the presence of large amounts of superoxide-dismutase-insensitive Cyt c reductase confounded attempts to use Cyt c to measure superoxide synthesis. With the partially solubilized membrane protein, direct reduction of lucigenin probably contributed to the chemiluminescence. Superoxide synthesis detected with lucigenin should be confirmed by superoxide-dismutase-sensitive Cyt c reduction.
Journal Article↗
Sources of sentence constraint on lexical ambiguity resolution.
Results from a series of naming experiments demonstrated that major lexical categories of simple sentences can provide sources of constraint on the interpretation of ambiguous words (homonyms). Manipulation of verb (Experiment 1) or subject noun (Experiment 2) specificity produced contexts that were empirically rated as being strongly biased or ambiguous. Priming was demonstrated for target words related to both senses of a homonym following ambiguous sentences, but only contextually appropriate target words were primed following strongly biased dominant or subordinate sentences. Experiment 3 showed an increase in the magnitude of priming when multiple constraints on activation converged. Experiments 4 and 5 eliminated combinatorial intralexical priming as an alternative explanation. Instead, it was demonstrated that each constraint was influential only insofar as it contributed to the overall semantic representation of the sentence. When the multiple sources of constraint were retained but the sentence-level representation was changed (Experiment 4) or eliminated (Experiment 5), the results of Experiments 1, 2, and 3 and were not replicated. Experiment 6 examined the issue of homonym exposure duration by using an 80-msec stimulus onset asynchrony. The results replicated the previous experiments. The overall evidence indicates that a sentence context can be made strongly and immediately constraining by the inclusion of specific fillers for salient lexical categories. The results are discussed within a constraint-based, context-sensitive model of lexical ambiguity resolution.
Analysis of Variance↗
Characterization and modulation of LP(a) in human hepatoma HEPG2 cells.
HepG2 cells have been widely used to study factors which affect the secretion of apoB100 lipoprotein particles. The objectives of this study were to determine if Lp(a) particles were present in conditioned medium from HepG2 cells and if so, was this accumulation affected by factors which alter apoB100 lipoprotein metabolism. The data demonstrate that Lp(a) accumulated in the medium in a time dependent manner over a 48 h incubation period. Ultracentrifugation fractionation and Western blot analysis demonstrated that lipoprotein particles containing apo(a) in complex with apoB100 were present at a density consistent with human plasma Lp(a). Incubation of the HepG2 cells with LDL or VLDL caused increases in Lp(a) accumulation in the medium (+33% +/- 14%, P NS and 56% +/- 21%, P < 0.05, respectively). In contrast, apo(a) mRNA decreased (-17% +/- 3%, P < 0.01 for both LDL and VLDL incubation). Increasing concentrations of amino acids in the medium resulted in progressively less Lp(a) and apoB100 in the medium, the effect being greater on apoB100. ApoB100 mRNA levels decreased with incubation of HepG2 cells with amino acids (-22% +/- 10%, P < 0.06) whereas apo(a) mRNA levels increased significantly (+47% +/- 14%, P < 0.005). Taken together, our data show that HepG2 cells express mRNA for apo(a), and accumulate Lp(a) in the medium. The close correlation of medium Lp(a) levels with medium apoB100 levels, and not with apo(a) mRNA levels, suggests that medium Lp(a) accumulation may be a function of lipoprotein synthesis and secretion and is consistent with extracellular assembly of Lp(a) lipoprotein particles.
Amino Acids↗
A risk index for pregnancy during anesthesia.
STUDY OBJECTIVE: To determine the validity of limiting pregnancy testing only to females older than 14 years, hypothesizing that (1) if this recommendation were valid, we would find no incidence of pregnant patients receiving anesthesia in our department under age 15, and (2) by identifying all patients receiving anesthesia while pregnant versus those who are not pregnant might allow calculation of a relative risk index for pregnancy per age group. DESIGN: A retrospective chart review. SETTING: Department of Anesthesiology at Louisiana State University Medical Center in Shreveport. MEASUREMENTS AND MAIN RESULTS: The relative numbers and ages of 1) all male versus female patients treated, 2) females presenting with viable pregnancy receiving anesthetic care, and 3) ages of conception in the youngest females were quantified to 4) correlate relative rates for pregnancy/anesthetic at each age. Of 16,033 anesthetics administered, 1,849 pregnant patients ages 13 to 44 years received 1,968 anesthetics (12.5% of total). One patient conceived at the age of 12. The rates of pregnant 13 (n = 4) and 14 (n = 24) year-olds in our anesthetized population equaled rates found with patients in the third and fourth decades of life, respectively. CONCLUSIONS: Louisiana State University Medical Center's current departmental guideline to preoperatively test all patients aged 12 to 44 years is supported by the desire to identify pregnancy prior to anesthesia and the encountered pregnancy distribution and incidence. Although radiation is a known danger to fetal development, our radiology department tests only females who "fail to confirm in writing a nonpregnant state." While females younger than 15 years deserve the same consideration as 30- and 40-year-old patients, multiple ethical, pragmatic, economic, and theoretical considerations may mitigate the need for mandatory testing of all patients.
Adolescent↗
A proposal for minimum detectable compartment in MIRD dosimetry modelling.
The accuracy of radiation dose estimates from radiopharmaceutical administrations has recently become more important for three main reasons: (i) clinical providers are demanding more information on diagnostic procedures; (ii) regulatory groups are scrutinizing dosimetry for research subjects; and (iii) accurate organ doses are crucial in therapeutic administrations. These dose estimates are a sensitive function of the residence times. Because most clinical data acquisition protocols are limited to the first 24 h after dose administration, the area under the remainder of the time-activity curve (TAC) must be estimated. Estimation methods range from assuming physical decay only (overly conservative) to extrapolating end point physiological kinetics (overly liberal). This study demonstrates how much the results from these two methods vary and develops an alternative method which more accurately estimates this remainder term. A method, called the minimum detectable compartment (MDC), is constructed so that an accurate dose estimate can be made with a realistic measure of the remainder term. The method for determining MDC uses standard hypothesis testing. Using an analogue of the traditional minimal detectable activity calculation, a model with and without constant compartments is fitted to the TAC. The size of the constant compartment is varied until the relative likelihood of the two models meets the desired measure of power and sensitivity. Computer simulations of a simple mono-exponential are used to demonstrate the MDC as a function of the model, the number of data points, the range of the data and the noise in the data. The MDC is a very sensitive function of the data range. It falls by more than 50% when the data range is increased from two to three half-lives. In addition, the MDC is moderately sensitive to the noise in the data and relatively insensitive to the number of data points. These findings suggest that the MDC method can also be uses a priori to indicate what type of data collection regimen is necessary to achieve a certain accuracy.
Humans↗
The role of interleukin-2, interleukin-12, and dendritic cells in cancer therapy.
PURPOSE: Recombinant interleukin-2 (rIL-2) administration can mediate regression of solid tumors in patients with melanoma and renal cell carcinoma. A better understanding of the mechanisms of rIL-2-mediated antitumor effects has led to the investigation of novel immunotherapeutic approaches. Two approaches that appear promising include administration of antigen-pulsed dendritic cells (DC) and administration of DC or genetically engineered fibroblasts expressing human interleukin-12 (IL-12). The rationale for these immunotherapeutic approaches and preliminary clinical studies are presented. PATIENTS AND METHODS: We have conducted a pilot study to evaluate the feasibility of treating melanoma patients with peptide-pulsed DC. Six melanoma patients received 1 to 3 x 10(6) DC pulsed with synthetic melanoma antigenic peptides. The peptide-pulsed DC were infused weekly for 4 weeks. We have also treated 32 patients in a phase I/II trial with IL-12-producing fibroblasts. Patients received escalating doses of cells weekly for 4 weeks, which produced quantities of IL-12 ranging from 10 ng to 9 micrograms/24 hours. RESULTS: Infusion of melanoma peptide-pulsed DC produced a complete response in one patient, and significant T-cell and DC infiltration of melanoma lesions was observed. Lesional and regional responses have been observed in patients with melanoma, head and neck carcinoma, and breast cancer who received intralesional injections of IL-12-producing fibroblasts. Phase II studies of this approach are planned and will be initiated in the next few months. CONCLUSIONS: These studies confirm the feasibility of these novel immunotherapeutic approaches and demonstrate their potential antitumor activity. These approaches may be effective in patients with metastatic melanoma and other solid tumors, and they may ultimately be used to improve the efficacy of rIL-2-based immunotherapy.
Carcinoma, Renal Cell↗
The effect of individual amino acids on ApoB100 and Lp(a) secretion by HepG2 cells.
The rate at which HepG2 cells secrete apoB100 lipoproteins is inversely related to the concentration of amino acids in the medium (Zhang, Z., Sniderman, A. D., Kalant, D., Vu, H., Monge, J. C., Tao, Y., and Cianflone, K. (1993) J. Biol. Chem. 268, 26920-26926). The purpose of the present study was to determine the effect of individual amino acids on apoB100 and lipoprotein secretion. Asparagine was associated with modestly increased secretion. The branched chain amino acids (leucine, isoleucine, and valine) and lysine had minor inhibitory effects. The other amino acids, by contrast, decreased apoB secretion, although the magnitude of the effect varied considerably, the most potent being tyrosine, cysteine, phenylalanine, tryptophan, methionine, and glutamine. Although the effect on Lp(a) generally paralleled that on apoB100, it was usually much less pronounced. No amino acid caused a marked decrease in albumin, apoAI, or total protein secreted from the HepG2 cells. The amino acid effect on apoB was paralleled by similar decreases in secreted cholesterol ester (CE) primarily in the low density lipoprotein density range (d < 1.006-1.063 g/ml), although there was no significant change in intracellular CE. Neither intracellular nor secreted triglycerides (TG) or free cholesterol changed, resulting in a slightly larger TG-enriched particle being secreted. The effect was confirmed in cultured primary hamster hepatocytes, where a mixture of amino acids also caused a decrease in apoB secretion (up to 40%). ApoAI appeared to increase as with the HepG2 cells. Secreted CE paralleled apoB . There was no change in intracellular or secreted TG or free cholesterol, resulting in a substantially larger TG-rich particle being secreted. mRNA for apoB100 increased with asparagine, decreased moderately with branched chain amino acids, and decreased further with glutamine, as shown by dot blot and Northern blotting. Pulse-chase studies indicated that there was no change in apoB secretion efficiency under any condition. These results extend our previous observations by demonstrating specificity of the amino acid effect on apoB100 secretion. Although an effect on transcription is the likely mechanism, the exact basis for this remains to be determined.
Amino Acids↗