Biomedical subjects

A Nguyen

Publications and source records attributed to A Nguyen.

At least 19 recordsLinked to original sources

PubMed2006

The expression of apolipoprotein B epitopes is normal in LDL of diabetic and end-stage renal disease patients.

AIMS/HYPOTHESIS: When LDLs are exposed to glucose in vitro, glycation of apolipoprotein B100 (apoB) leads to a loss in its affinity for the LDL receptor and reproducible alterations in the immunoreactivity of specific apoB epitopes, including several epitopes close to the LDL receptor binding site. The aim of this work was to determine if similar immunological changes are observed in vivo in LDLs of diabetic and end-stage renal disease (ESRD) patients. SUBJECTS, MATERIALS AND METHODS: The immunoreactivity of LDLs isolated from 14 diabetic patients with normal renal function and 13 patients with ESRD was studied with a panel of 25 well-characterised anti-apoB monoclonal antibodies. RESULTS: Although diabetic and ESRD LDLs showed evidence of glycation modification, none of the changes in the apoB immunoreactivity induced by glucose in vitro was observed in vivo, including those for epitopes close to the LDL receptor binding domain. CONCLUSIONS/INTERPRETATION: These results suggest that in vivo glycation of LDLs is a complex process that is not mimicked by in vitro exposure of LDLs to high concentrations of glucose. This questions the clinical significance of the in vitro glycation studies used to understand the pathophysiological consequences of LDL glycation in diabetes and ESRD.

Apolipoproteins B↗

PubMed2005

Exhaled breath condensate pH assays are not influenced by oral ammonia.

BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) is robust and simple. Acidic source fluid (airway lining fluid) traps bases while volatilising acids, leading to EBC acidification in many lung diseases. Lower airway ammonia is one determinant of airway lining fluid pH, raising the concern that addition of the base ammonia by contamination from the mouth might confound EBC pH assays. METHODS: Three discrete methods were used to limit oral ammonia contamination of EBC collections: endotracheal intubation, oral rinsing, and -40 degrees C condenser temperatures. Separately, ammonia was removed from collected EBC samples by lyophilisation and resuspension. Intraweek and intraday variability of ammonia concentration was determined in 76 subjects, and ammonia and pH from a further 235 samples were graphically compared. Ammonia was assayed spectrophotometrically and pH was assessed after deaeration. RESULTS: Data from 1091 samples are presented. Ammonia was reduced in EBC by all methods. Endotracheal intubation decreased EBC ammonia from a mean (SD) of 619 (124) microM to 80 (24) microM (p<0.001, n=32). Oral rinsing before collection also led to a decline in EBC ammonia from 573 (307) microM to 224 (80) microM (p=0.016, n=7). The colder the condensation temperature used, the less ammonia was trapped in the EBC. Lyophilisation removed 99.4 (1.9)% of ammonia. Most importantly, the pH of EBC never decreased after removal of ammonia by any of these methods. Intraweek and intraday coefficients of variation for ammonia were 64 (27)% and 60 (32)%, which is substantially more variable than EBC pH assays. CONCLUSIONS: Although ammonia and pH appear to correlate in EBC, the oral ammonia concentration is not an important determinant of EBC pH. No precautions need to be taken to exclude oral ammonia when EBC pH is of interest. The low pH and low ammonia found in EBC from patients with lung diseases appear to be independent effects of volatile compounds arising from the airway.

Adult↗

PubMed2004

Characteristics of women who deliver with no prenatal care.

OBJECTIVE: To compare the characteristics, morbidities and pregnancy outcomes of women with no prenatal care and women receiving some care. METHODS: Medical records were abstracted for demographic variables as well as information concerning substance abuse, sexually transmitted diseases and perinatal outcome. Bivariate associations of descriptive data were tested using odds ratios or Fisher's exact test. Multivariate analysis determined adjusted odds ratios. Significance was set at alpha=0.05. RESULTS: Women who received no prenatal care were more likely to be multiparous, living with at least one child, less educated, uninsured, smoke, use cocaine and have a prior history of substance abuse. Preterm labor, preterm delivery, low birth weight and stillbirth were more common. Syphilis and HIV were found in nearly 5% of women without care. CONCLUSION: Intensive interventions are needed for women who fail to receive prenatal care so as to link these high-risk women to needed services.

Adult↗

PubMed2004

Suppurative rhinitis associated with Haemophilus species infection in a cat.

A young cat with signs of chronic rhinitis was evaluated for underlying anatomical, inflammatory, or infectious disease. Initial diagnostics were significant for the isolation of an unusual pathogen, Haemophilus species. Isolation using a human RapID NH system erroneously identified the isolate as H. segnis, a human pathogen. No database of veterinary pathogens (Haemophilus) are included in the system and animal pathogens will either be erroneously identified or yield a unique biocode not listed. Because of the unique nature of the pathogen we explored the possibility of immunosuppression as a contributory factor to infection. A variety of laboratory tests were employed to evaluate immune function. The clinical indications and utility of immune function testing are discussed. No immune dysfunction was identified.

Animals↗

PubMed2002

Dalitz plot analysis of the decay D(+)-->K(-)pi(+)pi(+) and indication of a low-mass scalar Kpi resonance.

We study the Dalitz plot of the decay D(+)-->K(-)pi(+)pi(+) with a sample of 15090 events from Fermilab experiment E791. Modeling the decay amplitude as the coherent sum of known Kpi resonances and a uniform nonresonant term, we do not obtain an acceptable fit. If we allow the mass and width of the K(*)(0)(1430) to float, we obtain values consistent with those from PDG but the chi(2) per degree of freedom of the fit is still unsatisfactory. A good fit is found when we allow for the presence of an additional scalar resonance, with mass 797+/-19+/-43 MeV/c(2) and width 410+/-43+/-87 MeV/c(2). The mass and width of the K(*)(0)(1430) become 1459+/-7+/-5 MeV/c(2) and 175+/-12+/-12 MeV/c(2), respectively. Our results provide new information on the scalar sector in hadron spectroscopy.

Journal Article↗

PubMed2002

Concurrent measurement of the survival of two populations of rabbit platelets labeled with either two PKH lipophilic dyes or two concentrations of biotin.

BACKGROUND: To avoid radioisotopic labeling and permit comparison of the survival of two platelet populations concurrently in one animal, we compared simultaneous recoveries and survival times of homologous rabbit platelets labeled in vitro with the lipophilic dyes PKH26 (red fluorescing) and PKH67 (green fluorescing) and with two levels of biotin (low, 1 microg/ml; high, 10 microg/ml). METHODS: Blood samples were drawn up to 96 h postinfusion and analyzed by flow cytometry. Biotin-labeled samples were incubated with phycoerythrin-streptavidin before analysis. RESULTS: Recovery of PKH26-labeled platelets at 1 h was lower (37.5%) than that of PKH67-labeled platelets (47.3%; P < 0.001). Platelet survival times were 62.4 and 61.9 h. Recoveries at 1 h of platelets labeled with two levels of biotin were similar (86.6% and 84.6%) and greater than those of PKH-labeled platelets (P < 0.001). Survival of platelets labeled with biotin did not differ (low, 83.3 h; high, 85.2 h) and was longer than for PKH-labeled platelets (P < 0.01). Labeling methods did not activate platelets (measured by P-selectin expression), nor did they affect platelet responses to adenosine diphosphate (ADP), collagen, or thrombin. CONCLUSIONS: Labeling with two levels of biotin is superior to labeling with PKH dyes, and is useful for measuring concurrently the survival of two differing platelet populations.

Adenosine Diphosphate↗

PubMed2002

Synthetic neuromelanin is toxic to dopaminergic cell cultures.

In the present study, primary cultures of mesencephalic dopaminergic cells were exposed to synthetic dopamine neuromelanin (NM) for 48 hrs at concentrations of 0, 1, 10, 20, 50 and 100 microg NM/ml medium. Differently prepared synthetic NM with or without incorporated iron and NM oxidatively damaged by hydrogen peroxide were used. All NMs affected cellular structures e.g. as swelling of neural processes, rounding of cells, and occasional inclusion of neuromelanin particles. Cell numbers were uniformly and dose dependently reduced. Exposure to MPP(+) and ferric iron led to cytotoxic changes which could be further aggravated by oxidatively damaged NM, suggesting cytotoxicity of soluble compounds of NM in predamaged neurons.

1-Methyl-4-phenylpyridinium↗

PubMed2001

Direct measurement of the pion valence-quark momentum distribution, the pion light-cone wave function squared.

We present the first direct measurements of the pion valence-quark momentum distribution which is related to the square of the pion light-cone wave function. The measurements were carried out using data on diffractive dissociation of 500 GeV/c pi(-) into dijets from a platinum target at Fermilab experiment E791. The results show that the /q&q> light-cone asymptotic wave function describes the data well for Q2 approximately 10 (GeV/c)(2) or more. We also measured the transverse momentum distribution of the diffractive dijets.

Journal Article↗

PubMed2001

Observation of color-transparency in diffractive dissociation of pions.

We have studied the diffractive dissociation into dijets of 500 GeV/c pions scattering coherently from carbon and platinum targets. Extrapolating to asymptotically high energies (where t(min)-->0), we find that when the per-nucleus cross section for this process is parametrized as sigma = sigma0Aalpha, alpha has values near 1.6, the exact result depending on jet transverse momentum. These values are in agreement with those predicted by theoretical calculations of color-transparency.

Journal Article↗

PubMed2001

Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeast.

Multicellular organisms must have means of preserving their genomic integrity or face catastrophic consequences such as uncontrolled cell proliferation or massive cell death. One response is a modification of nuclear proteins by the addition and removal of polymers of ADP-ribose that modulate the properties of DNA-binding proteins involved in DNA repair and metabolism. These ADP-ribose units are added by poly(ADP-ribose) polymerase (PARP) and removed by poly(ADP-ribose) glycohydrolase. Although budding yeast Saccharomyces cerevisiae does not possess proteins with significant sequence similarity to the human PARP family of proteins, we identified novel small molecule inhibitors against two family members, PARP1 and PARP2, using a cell-based assay in yeast. The assay was based on the reversal of growth inhibition caused by the heterologous expression of either PARP1 or PARP2. Validation of the assay was achieved by showing that the growth inhibition was relieved by a mutation in a single residue in the catalytic site of PARP1 or PARP2 or exposure of yeast to a known PARP1 inhibitor, 6(5H)-phenanthridinone. In separate experiments, when a putative protein regulator of PARP activity, human poly(ADP-ribose) glycohydrolase, was coexpressed with PARP1 or PARP2, yeast growth was restored. Finally, the inhibitors identified by screening the yeast assay are active in a mammalian PARP biochemical assay and inhibit PARP1 and PARP2 activity in yeast cell extracts. Thus, our data reflect the strength of using yeast to identify small molecule inhibitors of therapeutically relevant gene families, including those that are not found in yeast, such as PARP. The resultant inhibitors have two critical uses (a) as leads for drug development and (b) as tools to dissect cellular function.

ATP-Binding Cassette Transporters↗

PubMed2001

Search for rare and forbidden Charm Meson decays D0 --> Vl+l- and hhll.

We report results of a search for flavor-changing neutral current (FCNC), lepton flavor, and lepton-number violating decays of the D0 (and its antiparticle) into three and four bodies. Using data from Fermilab charm hadroproduction experiment E791, we examine modes with two leptons (muons or electrons) and a rho(0), K( *0), or straight phi vector meson or a nonresonant pi(pi), Kpi, or KK pair of pseudoscalar mesons. No evidence for any of these decays is found. Therefore, we present branching-fraction upper limits at 90% confidence level for the 27 decay modes examined (18 new).

Journal Article↗

PubMed2001

Study of the D(+)(s)-->pi(-)pi(+)pi(+) decay and measurement of f(0) masses and widths.

From a sample of 848+/-44 D(+)(s)-->pi(-)pi(+)pi(+) decays, we find gamma(D(+)(s)-->pi(-)pi(+)pi(+))/gamma(D(+)(s)-->straight phipi(+)) = 0.245+/-0.028(+0.019)(-0.012). Using a Dalitz plot analysis of this three body decay, we find significant contributions from the channels rho(0)(770)pi(+), rho(0)(1450)pi(+), f(0)(980)pi(+), f(2)(1270)pi(+), and f(0)(1370)pi(+). We also present the values obtained for masses and widths of the resonances f(0)(980) and f(0)(1370).

Journal Article↗

PubMed2001

Experimental evidence for a light and broad scalar resonance in D(+) --> pi(-)pi(+)pi(+) decay.

From a sample of 1172 +/- 61 D(+)-->pi(-)pi(+)pi(+) decays, we find gamma(D(+)-->pi(-)pi(+)pi(+))/gamma(D(+)-->K-pi(+)pi(+)) = 0.0311 +/- 0.0018(+0.0016)(-0.0026). Using a coherent amplitude analysis to fit the Dalitz plot of these decays, we find strong evidence that a scalar resonance of mass 478(+24)(-23) +/- 17 MeV/c(2) and width 324(+42)(-40) +/- 21 MeV/c(2) accounts for approximately half of all decays.

Journal Article↗

PubMed2001

Scalp nerve blocks decrease the severity of pain after craniotomy.

UNLABELLED: Up to 80% of patients report moderate to severe pain after craniotomy. In this study, we assessed the efficacy of scalp block for decreasing postoperative pain in brain surgery. Thirty patients scheduled for supratentorial craniotomy were enrolled. They were randomly divided into two groups: Ropivacaine (scalp block with 20 mL of ropivacaine 0.75%) and Saline (scalp block with 20 mL of saline 0.9%). Anesthesia was standardized. The scalp block was performed after skin closure and before awakening. Postoperative pain was assessed at 4, 8, 12, 16, 20, 24, and 48 h by using a 10-cm visual analog scale. Analgesia was provided with sub- cutaneous codeine as requested by the patient. Average visual analog scale scores were higher in the Saline group as compared with Ropivacaine (3.7 +/- 2.4 vs 2.0 +/- 1.6; P = 0.036). The total dose of codeine did not differ, nor did the duration of time before the first dose of codeine was required in the Ropivacaine (571 +/- 765 min) versus Saline (319 +/- 409 min; P = 0.17) group. In conclusion, we found that postoperative scalp block decreases the severity of pain after craniotomy and that this effect is long lasting, possibly through a preemptive mechanism. IMPLICATIONS: Up to 80% of patients report moderate to severe pain after craniotomy. This randomized double-blinded study demonstrated that ropivacaine scalp block decreases the severity of pain after supratentorial craniotomy.

Adolescent↗

PubMed2001

A streamlined process to phenotypically profile heterologous cDNAs in parallel using yeast cell-based assays.

To meet the demands of developing lead drugs for the profusion of human genes being sequenced as part of the human genome project, we developed a high-throughput assay construction method in yeast. A set of optimized techniques allows us to rapidly transfer large numbers of heterologous cDNAs from nonyeast plasmids into yeast expression vectors. These high- or low-copy yeast expression plasmids are then converted quickly into integration-competent vectors for phenotypic profiling of the heterologous gene products. The process was validated first by testing proteins of diverse function, such as p38, poly(ADP-ribose) polymerase-1, and PI 3-kinase, by making active-site mutations and using existing small molecule inhibitors of these proteins. For less well-characterized genes, a novel random mutagenesis scheme was developed that allows a combination selection/screen for mutations that retain full-length expression and yet reverse a growth phenotype in yeast. A broad range of proteins in different functional classes has been profiled, with an average yield for growth interference phenotypes of approximately 30%. The ease of manipulation of the yeast genome affords us the opportunity to approach drug discovery and exploratory biology on a genomic scale and shortens assay development time significantly.

Amino Acid Sequence↗

PubMed2001

SNP genotyping by multiplexed solid-phase amplification and fluorescent minisequencing.

The emerging role of single-nucleotide polymorphisms (SNPs) in clinical association and pharmacogenetic studies has created a need for high-throughput genotyping technologies. We describe a novel method for multiplexed genotyping of SNPs that employs PCR amplification on microspheres. Oligonucleotide PCR primers were designed for each polymorphic locus such that one of the primers contained a recognition site for BbvI (a type IIS restriction enzyme), followed by 11 nucleotides of locus-specific sequence, which reside immediately upstream of the polymorphic site. Following amplification, this configuration allows for any SNP to be exposed by BbvI digestion and interrogated via primer extension, four-color minisequencing. Primers containing 5' acrylamide groups were attached covalently to the solid support through copolymerization into acrylamide beads. Highly multiplexed solid-phase amplification using human genomic DNA was demonstrated with 57 beads in a single reaction. Multiplexed amplification and minisequencing reactions using bead sets representing eight polymorphic loci were carried out with genomic DNA from eight individuals. Sixty-three of 64 genotypes were accurately determined by this method when compared to genotypes determined by restriction-enzyme digestion of PCR products. This method provides an accurate, robust approach toward multiplexed genotyping that may facilitate the use of SNPs in such diverse applications as pharmacogenetics and genome-wide association studies for complex genetic diseases.

DNA↗

PubMed2001

Spirohydantoins from D-ribose as new potent enzymatic inhibitors.

Anomeric spirohydantoin derivatives from monosaccharides are known for various biological properties. We describe herein the synthesis of the 3-spirohydantoin derivatives of D-allose and D-ribose. The key step is the stereoselective glyco-alpha-aminonitrile formation from ulose derivatives of D-glucose and D-xylose using titanium tetra-isopropoxide as a mild and efficient catalyst. Target compounds were synthesized from these intermediates. The glucidic moiety was partially or totally deprotected under acidic conditions. These new heterocyclic monosaccharidic derivatives are potent glycogen phosphorylase inhibitors.

Enzyme Inhibitors↗

PubMed2001

Variable effects of transgenic c-Maf on autoimmune diabetes.

Autoimmune diabetes is associated with T helper 1 polarization, but protection from disease can be provided by the application of T helper 2 (Th2) cytokines. To test whether genetic manipulation of T-cells can provide protective Th2 responses, we developed transgenic mice in which T-cells express the interleukin-4-specific transcription factor c-Maf. When crossed with a transgenic model that combines a class II restricted T-cell receptor specific for influenza hemagglutinin with islet beta-cell expression of hemagglutinin, the c-Maf transgene provided significant protection from spontaneous autoimmunity but not from adoptively transferred diabetes. In a second transgenic model in which islet cells express the lymphocytic choriomeningitis virus nucleoprotein, the virus infection triggers autoimmune diabetes within a few weeks involving both CD4 and CD8 T-cells; here too transgenic c-Maf provided significant protection. Surprisingly, when the c-Maf transgene was backcrossed with the NOD model of spontaneous disease, no protection was evident. Thus, transgenic c-Maf can strongly influence autoimmune disease development in some models, but additional factors, such as background genetic differences, can influence the potency of its effect.

Animals↗