Search PubMed⌕ Search

Biomedical subjects

T T Nguyen

Publications and source records attributed to T T Nguyen.

At least 19 recordsLinked to original sources
PubMed2006

Thimet oligopeptidase (EC 3.4.24.15) activates CPI-0004Na, an extracellularly tumour-activated prodrug of doxorubicin.

CPI-0004Na is a tetrapeptidic extracellularly tumour-activated prodrug of doxorubicin. The tetrapeptide structure ensures blood stability and selective cleavage by unidentified peptidase(s) released by tumour cells. The purpose of this work was to identify the enzyme responsible for the first rate-limiting step of CPI-0004Na activation, initially attributed to a 70 kDa acidic (pI=5.2) metallopeptidase active at neutral pH that was subsequently purified from HeLa cell homogenates. Two electrophoretic bands were isolated and identified by matrix-assisted laser desorption ionisation-time of flight (MALDI-tof) and electrospray ionisation-quadrupole-time of flight (ESI-Q-tof) mass spectrometry as thimet oligopeptidase (TOP). The identity of the CPI-0004Na activating enzyme and TOP was further supported by the similar substrate specificity of the purified enzyme and recombinant TOP, by thiol stimulation of CPI-0004Na cleavage by cancer cell conditioned media (unique characteristic of TOP) and by the inhibition of CPI-0004Na activation by specific inhibitors or immunoprecipitation. Although other enzymes can be involved, TOP clearly appears to be a likely candidate for extracellular activation of the CPI-0004Na prodrug.

Antineoplastic Agents↗
PubMed2006

Continuum theory of retroviral capsids.

We present a self-assembly phase diagram for the shape of retroviral capsids, based on continuum elasticity theory. The spontaneous curvature of the capsid proteins drives a weakly first-order transition from spherical to spherocylindrical shapes. The conical capsid shape which characterizes the HIV-1 retrovirus is never stable under unconstrained energy minimization. Only under conditions of fixed volume and/or fixed spanning length can the conical shape be a minimum energy structure. Our results indicate that, unlike the capsids of small viruses, retrovirus capsids are not uniquely determined by the molecular structure of the constituent proteins but depend in an essential way on physical constraints present during assembly.

Animals↗
PubMed2006

Radiation hybrid mapping of 18 positional and physiological candidate genes for arthrogryposis multiplex congenita on porcine chromosome 5.

We report the chromosomal assignment of 18 porcine genes to human homologues using the INRA-Minnesota swine radiation hybrid panel (IMpRH). These genes (CACNA1C, COL2A1, CPNE8, C3F, C12ORF4, DDX11, GDF11, HOXC8, KCNA1, MDS028, TMEM106C, NR4A1, PHB2, PRICKLE1, Q6ZUQ4, SCN8A, TUBA8 and USP18) are located on porcine chromosome 5 (SSC5) and represent positional and functional candidates for arthrogryposis multiplex congenita (AMC), which maps to SSC5. CPNE8, PRICKLE1, Q6ZUQ4 and TUBA8 were mapped to the interval for pig AMC between microsatellites SW152 and SW904. Three SNPs in TUBA8 co-segregated with the AMC phenotype in 230 pigs of our research population without recombination and could be used as a genetic marker test for AMC. In addition, we provide evidence that a small chromosomal region of HSA22q11.2 evolutionarily corresponds to SSC5q12-q22 (and contains the human homologues of porcine SW152, Q6ZUQ4, TUBA8 and USP18), while the regions flanking HSA22q11.2 on SSC5 correspond to HSA12p13 and HSA12q12. We identified seven distinct chromosomal blocks, further supporting extensive rearrangements between genes on HSA12 and HSA22 in the AMC region on SSC5.

Animals↗
PubMed2005

Surface charge relaxation and the pearling instability of charged surfactant tubes.

The pearling instability of bilayer surfactant tubes was recently observed during the collapse of fluid monolayers of binary mixtures of Dimyristoylphosphocholine (DMPC): Palmitoyloleoylphosphoglycerol (POPG) and Dipalmitoylphosphocholine (DPPC):POPG surfactants. It can be explained by a Rayleigh-like instability under the action of the bilayer surface tension. The magnitude of surface tension is dictated by the electrostatic interaction between charged surfactants. Relaxation of charged molecules is proposed here as an additional mechanism driving the instability. We find the functional dependence of the electrostatic surface tension and relaxation energies on the screening length kappa(-1) explicitly. Relaxation lowers the cost of bending a tube into pearls making the cylindrical tube even more unstable. It is known that for the weak screening case in which the tube radius is smaller than the screening length of the solution, this effect is important. However, for the case of strong screening it is negligible. For the experiments mentioned, the situation is marginal. In this case, we show that the effect of relaxation remains small. It contributes about 20% to the total electrostatic energy.

Computer Simulation↗
PubMed2005

Elasticity theory and shape transitions of viral shells.

Recently, continuum elasticity theory has been applied to explain the shape transition of icosahedral viral capsids--single-protein-thick crystalline shells--from spherical to "buckled" or faceted as their radius increases through a critical value determined by the competition between stretching and bending energies of a closed two-dimensional (2D) elastic network. In the present work we generalize this approach to capsids with nonicosahedral symmetries, e.g., spherocylindrical and conical shells. One key additional physical ingredient is the role played by nonzero spontaneous curvature. Another is associated with the special way in which the energy of the 12 topologically required fivefold sites depends on the "background" local curvature of the shell in which they are embedded. Systematic evaluation of these contributions leads to a shape "phase" diagram in which transitions are observed from icosahedral to spherocylindrical capsids as a function of the ratio of stretching to bending energies and of the spontaneous curvature of the 2D protein network. We find that the transition from icosahedral to spherocylindrical symmetry is continuous or weakly first order near the onset of buckling, leading to extensive shape degeneracy. These results are discussed in the context of experimentally observed variations in the shapes of a variety of viral capsids.

Capsid↗
PubMed2005

Direct gene transfer in potato: a comparison of particle bombardment of leaf explants and PEG-mediated transformation of protoplasts.

Direct gene transfer methods in potato would facilitate the transfer of multiple genes and the manipulation of metabolic pathways in this species. In this study, up to 1.8 transformation events per shot (=0.5 per bombarded leaf) and 67.2 events per million protoplasts treated were obtained with particle bombardment and PEG-mediated direct DNA uptake, respectively. Limited disassociation of both HPT and GUS genes appeared to occur during the process of integration in only 19% of transformants. A large number of transformed potato plants with transgene expression at levels comparable to Agrobacterium-mediated transformation was obtained. High levels of GUS expression were only obtained in lines derived from PEG treatment. No correlation between the number of gene insertions and gene expression levels was found, suggesting that multiple insertions may have little or no effect on transgene expression.

Biolistics↗
PubMed2005

Application of bovine microsatellite markers for genetic diversity analysis of Swiss yak (Poephagus grunniens).

In order to assess the applicability of bovine microsatellite markers for population genetic studies in Swiss yak, 131 bovine microsatellite markers were tested on a panel of 10 animals. Efficient amplification was observed for 124 markers (94.6%) with a total of 476 alleles, of which 117 markers (94.3%) were polymorphic. The number of alleles per locus among the polymorphic markers ranged from two to nine. Seven loci (ILSTS005, BMS424B, BMS1825, BMS672, BM1314, ETH123 and BM6017) failed to amplify yak genomic DNA. Two cattle Y-chromosome specific microsatellite markers (INRA126 and BM861) amplified genomic DNA from both male and female yaks. However, two additional markers on cattle Y-chromosome (INRA124 and INRA189) amplified DNA from only males. Of the polymorphic markers, 24 microsatellites proposed by CaDBase for within- and cross-species comparisons and two additional highly polymorphic markers (MHCII and TGLA73) were used to investigate the genetic variability and the population structure of a Swiss yak herd that included 51 additional animals. The polymorphic information content ranged from 0.355 to 0.752, while observed heterozygosity (HO) ranged from 0.348 to 0.823. Furthermore, a set of 13 markers, organized into three multiplex polymerase chain reactions, was evaluated for routine parentage testing. This set provided an exclusion probability in a family of four yaks (both parents and two offspring) of 0.995. These microsatellites serve as useful tools for genetic characterization of the yak, which continues to be an important domestic livestock species.

Animals↗
PubMed2005

Application of bovine microsatellite markers on Saola (Pseudoryx nghetinhensis).

The aim of the present study was to assess the applicability of bovine microsatellite markers on Saola (Pseudoryx nghetinhensis). A total of 127 microsatellite markers were tested on a male and a young female Saola. An efficient amplification was observed for 123 markers (96.8%), 73 markers (59.3%) were polymorphic. Four loci (BM2304, BMS1928, BMS779 and ILSTS006) on cattle chromosomes 1, 4, 7 and 8, respectively, failed to amplify in Saola. Two cattle Y-chromosome-specific microsatellite markers (INRA126 and BM861) were successfully amplified from both sexes in Saola. However, two additional markers (INRA124 and INRA189) on Y-chromosome failed to amplify in the female animal. These results show that most of the bovine microsatellite markers are applicable in Saola and therefore they can be used to study the phylogenetic relationships and the genetic diversity of the Saola population.

Animals↗
PubMed2005

Characterization of G-banded chromosomes of a female saola (Pseudoryx nghetinhensis,2n = 50) and X chromosome i dentification by means of fluorescent in situ hybridization.

The saola (Pseudoryx nghetinhensis) is a newly discovered large mammal species, belongs to the subfamily Bovinae and is listed as being endangered. Due to the limitation of the material available, no cytogenetic studies have been carried out on this species. In the present study, preliminary cytogenetic analysis was undertaken on cultured female fibroblast cells to characterize the karyotype organization of saola. An examination of 120 Giemsa stained metaphases showed the diploid chromosome number of 2n = 50, including five bi-armed chromosome pairs. The distribution of constitutive heterochromatin in saola was studied. However, the variability in the size of C-bands was not significant on all the homologous chromosomes. The X chromosome pair, corresponding to the largest telocentric chromosomes, was identified by fluorescent in situ hybridization (FISH) using a bacterial artificial chromosome clone (BAC 0577G05, which maps to BTAXq25-->q33). In comparison to the standard karyotype of cattle (ISCNDB 2000), a G-banded ideogram of saola (about 390 band level) was presented. This work, therefore, provided a basic insight into the karyotype organization of this endangered species and will be particularly useful to improve the understanding of differences of genomes between related species.

Animals↗
PubMed2005

Laparoscopic esophagectomy.

Minimally invasive esophagectomy is emerging as an alternative option to open esophagectomy for benign and malignant esophageal diseases. This article provides a detailed review of the history of minimally invasive esophagectomy and an update on the currently accepted techniques for minimally invasive esophagectomy and its outcomes.

Esophagectomy↗
PubMed2004

A novel lipase/chaperone pair from Ralstonia sp. M1: analysis of the folding interaction and evidence for gene loss in R. solanacearum.

A microbial strain (referred to as M1) that produces an extracellular lipase was isolated from a soil sample in Vietnam, and identified as a Ralstonia species by partial sequencing of its 16S rDNA. A genomic library was constructed from Pst I fragments, and a colony showing lipase activity was selected for further analysis. Sequencing of the 4.7-kb insert in this clone (named M1-72) revealed one incomplete and three complete ORFs, predicted to encode a partial hypothetical glutaminyl tRNA synthetase (304 aa), a hypothetical transmembrane protein (500 aa), a lipase (328 aa) and a lipase chaperone (352 aa), respectively. Alignment of the insert sequence with the corresponding region of the genome of R. solanacearum GMI1000 (GenBank Accession No. AL646081) confirmed the presence in the latter of the genes for the hypothetical transmembrane protein and glutaminyl tRNA synthetase, which exhibited 89-91% identity to their counterparts in M1. However, R. solanacearum GMI1000 lacks the complete lipase-encoding gene and the major part of the chaperone-encoding gene, creating a so-called "black hole". The deduced amino acid sequences of the products of the lipase gene lipA and chaperone gene lipB from strain M1 shared 49.3-60.3% and 23.9-32.7% identity, respectively, with those of the Burkholderia lipase/chaperone subfamily I.2. lipB is located downstream of lipA, and separated from it by only 9 bp, and each gene has a putative ribosome binding site. The mature lipase LipA, a His-tagged derivative (LipAhis), the tagged full-length chaperone LipBhis and a truncated form (DeltaLipBhis) lacking the 56 N-terminal residues were expressed in Escherichia coli BL21. LipA, LipAhis and DeltaLipBhis could be expressed at high levels (70, 15 and 12 mg/g wet cells, respectively) and were easily purified. However, LipBhis was expressed at a much lower level which precluded purification. The specific activity of purified LipAhis, expressed on its own, was very low (<52 U/mg). However, after co-incubation with the purified DeltaLipBhis in vitro, the specific activity of the enzyme was markedly enhanced, indicating that the chaperone facilitated correct folding of the enzyme. A lipase:chaperone ratio of 1:10 was found to be optimal, yielding an enzyme preparation with a specific activity of 650 U/mg.

Amino Acid Sequence↗
PubMed2004

A method for matching the refractive index and kinematic viscosity of a blood analog for flow visualization in hydraulic cardiovascular models.

In this work, we propose a simple method to simultaneously match the refractive index and kinematic viscosity of a circulating blood analog in hydraulic models for optical flow measurement techniques (PIV, PMFV, LDA, and LIF). The method is based on the determination of the volumetric proportions and temperature at which two transparent miscible liquids should be mixed to reproduce the targeted fluid characteristics. The temperature dependence models are a linear relation for the refractive index and an Arrhenius relation for the dynamic viscosity of each liquid. Then the dynamic viscosity of the mixture is represented with a Grunberg-Nissan model of type 1. Experimental tests for acrylic and blood viscosity were found to be in very good agreement with the targeted values (measured refractive index of 1.486 and kinematic viscosity of 3.454 milli-m2/s with targeted values of 1.47 and 3.300 milli-m2/s).

Biomechanical Phenomena↗
PubMed2003

Profiling penciclovir susceptibility and prevalence of resistance of herpes simplex virus isolates across eleven clinical trials.

Asusceptibility testing program was established to determine the prevalence of resistance to penciclovir among herpes simplex virus isolates collected from patients participating in 11 world-wide clinical trials involving penciclovir (topical or intravenous formulations) or famciclovir, the oral prodrug of penciclovir. These trials represented nine randomised double blind, placebo or aciclovir-controlled studies and two open-label studies. Groups surveyed included immunocompetent or immunocompromised patients receiving 2 to 12 months chronic suppressive therapy for genital herpes, immunocompetent patients with recurrent herpes labialis treated for four days, and immunocompromised patients with mucocutaneous herpes simplex virus (HSV). Another subset of patients had been identified as non-responders to aciclovir or to valaciclovir. This program assessed the susceptibility profile for a total of 2145 herpes simplex virus isolates from 913 immunocompetent and 288 immunocompromised patients treated with penciclovir, famciclovir, aciclovir or placebo (depending on trial design). HSV isolates were tested for susceptibility to penciclovir using the plaque reduction assay (PRA) in MRC-5 cells. Resistance was defined as an IC(50)>or=2.0 microg/ml or an IC(50)> 10-fold above the wild type control virus IC(50) within that particular assay. Penciclovir-resistant HSV was isolated from 0.22% immunocompetent patients, and 2.1% of immunocompromised patients overall and therefore the frequency of penciclovir-resistant herpes simplex virus in the immunocompetent population approximates that of aciclovir-resistant herpesvirus reported previously. Penciclovir-resistant HSV isolates were more common in isolates from immunocompromised patients, consistent with aciclovir clinical experience. Treatment with penciclovir (intravenous formulation) was associated with the development of resistant HSV in only one severely immunocompromised patient (day 7 isolate IC(50) = 2.01 microg/ml), although treatment was effective and resulted in the complete clearance of the lesion by day 8. No patients receiving topical penciclovir developed treatment-associated penciclovir-resistant HSV, and a single immunocompromised patient developed resistant HSV upon treatment with oral famiciclovir.

Acyclovir↗
PubMed2003

Isolated intracranial infection with Mycobacterium avium complex.

UNLABELLED: Mycobacterium avium-M. complex (MAC) has been linked to devastating respiratory and systemic illnesses in patients, especially in those who are immunosuppressed. The purpose of this study is to describe a case of isolated central nervous system (CNS) infection with MAC. This is a single case report of a patient with isolated intracranial mycobacterial infection. SETTING: the patient was treated and the immunohistochemical investigations were undertaken at the National Institutes of Health in Bethesda, Maryland, USA. INTERVENTION: the patient initially was treated with a cocktail of antimycobacterial medications. However, because his disease was refractory, he underwent a suboccipital craniotomy and evacuation of his cerebellar mass. The patient was determined to have a low production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) when compared to normal values. Despite extensive radiographic imaging studies and biopsies, there was no evidence of another focus of MAC infection in this patient. We conclude that intracranial infectious lesions in patients such as ours should be treated with conventional systemic antibiotic regimens as the first-line of therapy. We suggest neurosurgical intervention in medically refractory cases of intracranial infections.

Adult↗
PubMed2002

Central venous catheter-related bacteremia due to Tsukamurella species in the immunocompromised host: a case series and review of the literature.

We report 6 cases of bacteremia due to Tsukamurella species, all of which were in immunosuppressed patients with indwelling central venous catheters (CVCs). Fewer than 20 cases of serious illness due to these gram-positive bacilli have been reported in the medical literature; these cases have mostly been ascribed to the species Tsukamurella paurometabola. Tsukamurella species are frequently misidentified as Rhodococcus or Corynebacterium species. We used high-performance liquid chromatography to identify these organisms to the genus level and 16S ribosomal RNA gene sequencing and DNA-DNA dot blots for species identification. Three of our isolates were identified as Tsukamurella pulmonis, 1 was identified as Tsukamurella tyrosinosolvans, and 1 was identified as a unique species. One isolate was not maintained long enough for species identification. All patients were successfully treated with antimicrobial therapy and CVC removal. Infection with this organism should be considered in the immunosuppressed patient with an indwelling CVC and gram-positive bacilli in the blood.

Actinomycetales↗
PubMed2002

Persistence length of a polyelectrolyte in salty water: Monte Carlo study.

We address the long standing problem of the dependence of the electrostatic persistence length l(e) of a flexible polyelectrolyte (PE) on the screening length r(s) of the solution within the linear Debye-Hückel theory. The standard Odijk, Skolnick, and Fixman (OSF) theory suggests l(e) proportional, variant r(2)s, while some variational theories and some computer simulations suggest l(e) proportional, variant r(s). In this paper, we use Monte Carlo simulations to study the conformation of a simple polyelectrolyte. Using four times longer PEs than in previous simulations and refined methods for the treatment of the simulation data, we show that the results are consistent with the OSF dependence l(e) proportional, variant r(2)s. The linear charge density of the PE, which enters in the coefficient of this dependence is properly renormalized to take into account local fluctuations.

Journal Article↗
PubMed2002

Model of inversion of DNA charge by a positive polymer: fractionalization of the polymer charge.

We model one strand of DNA by a one-dimensional lattice (ODL) of negative charges and consider the problem of inversion of its charge by a positive polyelectrolyte (PE). In the neutral state of the ODL-PE complex, each of the ODL charges is locally compensated by a PE charge. When an additional PE molecule is adsorbed by ODL, its charge gets fractionalized into monomer charges of defects (tails and arches) on the background of the perfectly neutralized ODL. Defects spread all over the ODL, eliminating the self-energy of PE. For DNA this fractionalization mechanism leads to a substantial inversion of charge, a phenomenon which is widely used for gene delivery.

DNA↗