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Biomedical subjects

D Nguyen

Publications and source records attributed to D Nguyen.

At least 19 recordsLinked to original sources
PubMed2006

Optimization of cardiac cine in the rat on a clinical 1.5-T MR system.

OBJECT: The overall goal was to study cardiovascular function in small animals using a clinical 1.5-T MR scanner optimizing a fast gradient-echo cine sequence to obtain high spatial and temporal resolution. MATERIALS AND METHODS: Normal rat hearts (n = 9) were imaged using a 1.5-T MR scanner with a spiral fast gradient-echo (fast field echo for Philips scanners) sequence, three Cartesian fast gradient-echo (turbo field echo for Philips scanners) sequences with different in-plane resolution, and with and without flow compensation and half-Fourier acquisition. The hearts of four rats were then excised and left-ventricle mass was weighed. Inter- and intra-observer variability analysis was performed for magnetic resonance imaging (MRI) measurements. RESULTS: Half-Fourier acquisition with flow compensation gave the best sequence in terms of image quality, spatial as well as temporal resolution, and suppression of flow artifact. Ejection fraction was 71 +/- 4% with less than 5% inter- and intra-observer variability. A good correlation was found between MRI-calculated left-ventricular mass and wet weight. CONCLUSIONS: Using optimized sequences on a clinical 1.5-T MR scanner can provide accurate quantification of cardiac function in small animals and can promote cardiovascular research on small animals at 1.5-T.

Algorithms↗
PubMed2006

Developmental changes in Ca2+-regulated functions of early postnatal Purkinje neurons.

Ca(2+) influx through L-type Ca(2+) channels regulates several different cellular processes in developing Purkinje neurons, including activation of transcription factors and expression of cellular proteins. In the current studies, we examined the age dependence of these actions of Ca(2+) during the early developmental period. Purkinje neurons acutely isolated from postnatal day 4-8 rat pups were studied. We also examined the sensitivity of the Ca(2+)-regulated processes to a toxic environmental factor (ethanol) known to show age-dependent actions on developing Purkinje neurons. Results show that Ca(2+) activation of the transcription factor cAMP-responsive element binding protein (CREB) and Ca(2+)-induced alterations in the level of the apoptotic enzyme caspase 3 show both dose and age dependence in the early-developing Purkinje neurons. Interestingly, the age dependence was opposite for the two proteins. Ca(2+) regulation of calbindin, a Ca(2+) binding protein, was dose dependent but showed little age dependence. Exposure to ethanol altered Ca(2+) activation of pCREB in an age-dependent manner but did not alter Ca(2+) regulation of caspase 3 or calbindin levels. Taken together, these results show that the downstream effects of Ca(2+) signaling have age-dependent components during early Purkinje neuron development. This age dependence may play an important role in the normal developmental program and could contribute to the critical window of sensitivity observed for certain toxic agents during early development.

Age Factors↗
PubMed2004

Current status of cardiac MRI in small animals.

Cardiac magnetic resonance imaging (MRI) on small animals is possible but remains challenging and not well standardized. This publication aims to provide an overview of the current techniques, applications and challenges of cardiac MRI in small animals for researchers interested in moving into this field. Solutions have been developed to obtain a reliable cardiac trigger in both the rat and the mouse. Techniques to measure ventricular function and mass have been well validated and are used by several research groups. More advanced techniques like perfusion imaging, delayed enhancement or tag imaging are emerging. Regarding cardiac applications, not only coronary ischemic disease but several other pathologies or conditions including cardiopathies in transgenic animals have already benefited from these new developments. Therefore, cardiac MRI has a bright future for research in small animals.

Animals↗
PubMed2004

Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy.

This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical presentation than patients with mesial temporal sclerosis. Genetic studies of these mostly French Canadian families should help confirm the existence of a distinct syndrome.

Adolescent↗
PubMed2004

Daily rhythm and regulation of clock gene expression in the rat pineal gland.

Rhythms in pineal melatonin synthesis are controlled by the biological clock located in the suprachiasmatic nuclei. The endogenous clock oscillations rely upon genetic mechanisms involving clock genes coding for transcription factors working in negative and positive feedback loops. Most of these clock genes are expressed rhythmically in other tissues. Because of the peculiar role of the pineal gland in the photoneuroendocrine axis regulating biological rhythms, we studied whether clock genes are expressed in the rat pineal gland and how their expression is regulated.Per1, Per3, Cry2 and Cry1 clock genes are expressed in the pineal gland and their transcription is increased during the night. Analysis of the regulation of these pineal clock genes indicates that they may be categorized into two groups. Expression of Per1 and Cry2 genes shows the following features: (1) the 24 h rhythm persists, although damped, in constant darkness; (2) the nocturnal increase is abolished following light exposure or injection with a beta-adrenergic antagonist; and (3) the expression during daytime is stimulated by an injection with a beta-adrenergic agonist. In contrast, Per3 and Cry1 day and night mRNA levels are not responsive to adrenergic ligands (as previously reported for Per2) and daily expression of Per3 and Cry1 appears strongly damped or abolished in constant darkness. These data show that the expression of Per1 and Cry2 in the rat pineal gland is regulated by the clock-driven changes in norepinephrine, in a similar manner to the melatonin rhythm-generating enzyme arylalkylamine N-acetyltransferase. The expression of Per3 and Cry1 displays a daily rhythm not regulated by norepinephrine, suggesting the involvement of another day/night regulated transmitter(s).

Adrenergic beta-Agonists↗
PubMed2004

[Paroxysmal dyspnoea in a healthy individual: the spontaneous pneumothorax].

In a healthy individual, a dyspnoea of abrupt onset raises the suspicion of a spontaneous pneumothorax. The clinical examination and standard chest X-ray usually permit the correct diagnosis. The risk of reccurence can be assessed by the clinical history and examination. The functional consequences (which can be lethal) and the risk of recurrence will guide the short- and long-term therapy.

Diagnosis, Differential↗
PubMed2003

[Arrhythmias of primary hypertrophic cardiomyopathy].

Primary hypertrophic cardiomyopathy is a genetic disease causing sarcomere dysfunction. The structural and functional myocardial changes combine to produce cardiac arrhythmias related to reentry phenomena and to triggered automatic activity. The commonest arrhythmias are atrial fibrillation and ventricular arrhythmias; junctional tachycardias via the bundle of Kent are rare. Atrial fibrillation and the Wolff-Parkinson-White syndrome are more commonly associated with certain genetic mutations. Their treatment is mainly based on medication with amiodarone or on radiofrequency ablation in cases of junctional tachycardia. Ventricular arrhythmias are mainly isolated ventricular extrasystoles and non-sustained ventricular tachycardia. The prognostic significance of the latter has been subject of debate for many years but recent studies report a poor prognosis with non-sustained ventricular tachycardia especially in the young patients. Sustained ventricular tachycardia and ventricular fibrillation, though life-threatening complications of hypertrophic cardiomyopathy, are rarely documented and justify implantation of an automatic defibrillator as the risk of recurrence is high. The main objective of the cardiologist in cases of primary hypertrophic cardiomyopathy is to identify the patient at high risk of sudden death. This requires analysis of several parameters: clinical, anatomical, haemodynamic, rhythmic, functional and genetic. The presence of at least two risk factors for sudden death justifies preventive measures. The implantation of an automatic defibrillator is the most reliable form of treatment.

Arrhythmias, Cardiac↗
PubMed2002

[Chemoradiotherapy in locally advanced cancers of the uterine neck. Retrospective study of 92 patients treated at the Institute Curie between 1986 and 1998]].

PURPOSE: The prognosis of locally advanced cervix cancers is poor with metastatic and local recurrence risks. Recent publications reported that concurrent chemotherapy and pelvic radiation increased local control compared to radiotherapy alone. Chemotherapy could also decrease metastatic recurrences. We report 92 cases of patients with locally advanced cervix cancer treated between 1986 and 1998 at the Institut Curie. PATIENTS AND METHODS: Concurrent chemoradiation was exclusive in 51 cases and added to surgery in 41 cases. Chemotherapy with 5FU-Cisplatin-Mitomycin C-Vindesin (protocol A) was performed for 43% of patients and 57% of them received 5FU-Cisplatin alone (protocol B). RESULTS: Median follow-up was 64 months (6-149 months). Five-year disease-free survival rate was 47% and local control rate was 70%. Disease-free survival was correlated with therapeutic response. After exclusive chemoradiation, the good responsive patients had a better DFS (54% vs 26%, p = 0.018). In the surgery group, those patients with sterilized lymph nodes and tumours had also a higher DFS (76% vs 47%, p = 0.036). Toxicity was higher with protocol A. CONCLUSION: From our study, it appears that local control of advanced cervix cancers is better with combined chemoradiotherapy but disease-free survival stays low according to the metastatic evolution. Metastasis without local recurrence remained frequent in our study. 5FU-CDDP chemotherapy has a lower toxicity and is as effective as 5FU-CDDP-Mitomycin C-Vindesin protocol, in association with radiotherapy.

Adult↗
PubMed2002

Microevolution of the direct repeat region of Mycobacterium tuberculosis: implications for interpretation of spoligotyping data.

The direct repeat (DR) region has been determined to be an important chromosomal domain for studying the evolution of Mycobacterium tuberculosis. Despite this, very little is known about microevolutionary events associated with clonal expansion and how such events influence the interpretation of both restriction fragment length polymorphism (RFLP) and spoligotype data. This study examined the structure of the DR region in three independently evolving lineages of M. tuberculosis with a combination of DR-RFLP, spoligotyping, and partial DNA sequencing. The results show that the duplication of direct variable repeat (DVR) sequences and single-nucleotide polymorphisms is rare; conversely, the deletion of DVR sequences and IS6110-mediated mutation is observed frequently. Deletion of either single or contiguous DVR sequences was observed. The deletion of adjacent DVR sequences occurred in a dependent manner rather than as an accumulation of independent events. Insertion of IS6110 into either the direct repeat or spacer sequences influenced the spoligotype pattern, resulting in apparent deletion of DVR sequences. Homologous recombination between adjacent IS6110 elements led to extensive deletion in the DR region, again demonstrating a dependent evolutionary mechanism. Different isolates from the same strain family and isolates from different strain families were observed to converge to the same spoligotype pattern. In conclusion, the binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of M. tuberculosis. This has important implications for molecular epidemiologic strain tracking and for the application of spoligotype data to phylogenetic analysis of M. tuberculosis isolates.

Bacterial Typing Techniques↗
PubMed2001

Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor.

Immunotherapy targeting for the induction of a T-cell-mediated antitumor response in patients with renal cell carcinoma (RCC) appears to hold significant promise. Here we describe a novel RCC vaccine strategy that allows for the concomitant delivery of dual immune activators: G250, a widely expressed RCC associated antigen; and granulocyte/macrophage-colony stimulating factor (GM-CSF), an immunomodulatory factor for antigen-presenting cells. The G250-GM-CSF fusion gene was constructed and expressed in Sf9 cells using a baculovirus expression vector system. The Mr 66,000 fusion protein (FP) was subsequently purified through a 6xHis-Ni2+-NTA affinity column and SP Sepharose/fast protein liquid chromatography. The purified FP retains GM-CSF bioactivity, which is comparable, on a molar basis, to that of recombinant GM-CSF when tested in a GM-CSF-dependent cell line. When combined with interleukin 4 (IL-4; 1000 units/ml), FP (0.34 microg/ml) induces differentiation of monocytes (CD14+) into dendritic cells (DCs) expressing surface markers characteristic for antigen-presenting cells. Up-regulation of mature DCs (CD83+CD19-; 17% versus 6%) with enhanced expression of HLA class I and class II antigens was detected in FP-cultured DCs as compared with DCs cultured with recombinant GM-CSF. Treatment of peripheral blood mononuclear cells (PBMCs) with FP alone (2.7 microg/10(7) cells) augments both T-cell helper 1 (Th1) and Th2 cytokine mRNA expression (IL-2, IL-4, GM-CSF, IFN-gamma, and tumor necrosis factor-alpha). Comparison of various immune manipulation strategies in parallel, bulk PBMCs treated with FP (0.34 microg/ml) plus IL-4 (1000 units/ml) for 1 week and restimulated weekly with FP plus IL-2 (20 IU/ml) induced maximal growth expansion of active T cells expressing the T-cell receptor and specific anti-RCC cytotoxicity, which could be blocked by the addition of anti-HLA class I, anti-CD3, or anti-CD8 antibodies. In one tested patient, an augmented cytotoxicity against lymph node-derived RCC target was determined as compared with that against primary tumor targets, which corresponded to an 8-fold higher G250 mRNA expression in lymph node tumor as compared with primary tumor. The replacement of FP with recombinant GM-CSF as an immunostimulant completely abrogated the selection of RCC-specific killer cells in peripheral blood mononuclear cell cultures. All FP-modulated peripheral blood mononuclear cell cultures with antitumor activity showed an up-regulated CD3+CD4+ cell population. These results suggest that GM-CSF-G250 FP is a potent immunostimulant with the capacity for activating immunomodulatory DCs and inducing a T-helper cell-supported, G250-targeted, and CD8+-mediated antitumor response. These findings may have important implications for the use of GM-CSF-G250 FP as a tumor vaccine for the treatment of patients with advanced kidney cancer.

Animals↗
PubMed2001

Differential expression and tissue distribution of parkin isoforms during mouse development.

Mutations of the parkin gene are a cause of autosomal recessive juvenile parkinsonism. Although the parkin gene has been isolated from mouse, rat, and human, little is known about its expression in neural and nonneural tissues during development. In this study, we used a polyclonal antibody to a peptide downstream of the parkin ubiquitin domain to investigate (1) the differential expression of parkin isoforms in protein extracts from fetal and adult mouse tissues, and (2) the distribution of parkin in mouse fetal tissues at different developmental stages and in adult CNS tissues. By Western blot analyses, at least three isoforms of parkin of 22, 50, and 55 kDa were differentially expressed in mouse tissues. The p22 and p50 isoforms were found in fetal and adult mouse CNS tissues, while the p55 isoform was found only in adult tissues. The p50 isoform is the predominant form in both fetal and adult tissues. Immunolocalization in mouse fetuses showed that parkin was expressed only after neuronal differentiation. Although parkin was localized throughout the cytoplasm, the highest level of parkin was found in the neurites of both fetal and adult neurons.

Age Factors↗
PubMed2001

The fidelity of human DNA polymerase gamma with and without exonucleolytic proofreading and the p55 accessory subunit.

Mutations in human mitochondrial DNA influence aging, induce severe neuromuscular pathologies, cause maternally inherited metabolic diseases, and suppress apoptosis. Since the genetic stability of mitochondrial DNA depends on the accuracy of DNA polymerase gamma (pol gamma), we investigated the fidelity of DNA synthesis by human pol gamma. Comparison of the wild-type 140-kDa catalytic subunit to its exonuclease-deficient derivative indicates pol gamma has high base substitution fidelity that results from high nucleotide selectivity and exonucleolytic proofreading. pol gamma is also relatively accurate for single-base additions and deletions in non-iterated and short repetitive sequences. However, when copying homopolymeric sequences longer than four nucleotides, pol gamma has low frameshift fidelity and also generates base substitutions inferred to result from a primer dislocation mechanism. The ability of pol gamma both to make and to proofread dislocation intermediates is the first such evidence for a family A polymerase. Including the p55 accessory subunit, which confers processivity to the pol gamma catalytic subunit, decreases frameshift and base substitution fidelity. Kinetic analyses indicate that p55 promotes extension of mismatched termini to lower the fidelity. These data suggest that homopolymeric runs in mitochondrial DNA may be particularly prone to frameshift mutation in vivo due to replication errors by pol gamma.

Base Pair Mismatch↗
PubMed2001

Practical prevention of vaginal and rectal transmission of HIV by adapting the oral defense: use of commercial lubricants.

HIV is transmitted to 6.4 million human beings per year and the majority of these transmissions are sexual. Condoms are highly effective and are recommended as the primary preventive. However, the fact that there are millions of sexual transmissions each year indicates that many people do not use condoms and that additional preventives are needed. The mechanisms of natural prevention of oral transmission by saliva may be adaptable to the susceptible vagina and rectum. The objective of our study was to reduce the sexual transmission of HIV by mimicking saliva's targeting of the transmitting infected leukocytes and any cell-free HIV in seminal fluid. The previously recommended anti-HIV topical microbicide, nonoxynol-9, has not prevented HIV transmission in humans, probably because it causes mucosal irritation and attracts CD4(+) cells. To identify effective preparations that are nonirritating, we studied the anti-HIV activity of commercially available, over-the-counter (OTC) lubricants and vaginal preparations that are judged safest by the U.S. Food and Drug Administration (FDA), and are nonirritating. The effect of OTC preparations on both the production of HIV by infected leukocytes and cell-free HIV suspended in seminal fluid was measured under simulated in vivo conditions. We surveyed 22 OTC vaginal preparations and excluded those with low inhibitory activity and those that were inhibitory but likely to be irritating. Three included preparations are highly active against both HIV-infected leukocytes suspended in seminal fluid and active against cell-free HIV, under in vitro conditions that simulate in vivo conditions. Since the preparations identified here as anti-HIV substances have the advantages of being widely available, inexpensive, acceptable, in the safest U.S. FDA category, and may be used by recipient women or men, they should be tested in clinical trials to help prevent sexual transmission of HIV.

Anti-HIV Agents↗
PubMed2001

Mutator effects of overproducing DNA polymerase eta (Rad30) and its catalytically inactive variant in yeast.

DNA polymerase eta synthesizes DNA in vitro with low fidelity. Based on this, here we report the effects of deletion or increased expression of yeast RAD30 gene, encoding for polymerase eta (Pol eta), on spontaneous mutagenesis in vivo. Deletion of RAD30 did not affect spontaneous mutagenesis. Overproduction of Rad30p was slightly mutagenic in a wild-type yeast strain and moderately mutagenic in strains with inactive 3'-->5'-exonuclease of DNA polymerase epsilon or DNA mismatch repair. These data suggest that excess Rad30p reduces replication fidelity in vivo and that the induced errors may be corrected by exonucleolytic proofreading and DNA mismatch repair. However, the magnitude of mutator effect (only up to 10-fold) suggests that the replication fork is protected from inaccurate synthesis by Pol eta in the absence of DNA damage. Overproduction of catalytically inactive Rad30p was also mutagenic, suggesting that much of the mutator effect results from indirect perturbation of replication rather than from direct misincorporation by Pol eta. Moreover, while excess wild-type Pol eta primarily induced base substitutions in the msh6 and pms1 strains, excess inactive Rad30p induced both base substitutions and frameshifts. This suggests that more than one mutagenic mechanism is operating when RAD30 is overexpressed.

Base Sequence↗
PubMed2001

Expression of the chemokine receptors CXCR1 and CXCR2 in rat oligodendroglial cells.

Chemokines are small proteins that act as chemoattractants and activators in leukocytes during physiological and inflammatory processes. In the CNS chemokine receptors have been shown to be expressed on neurons, astrocytes and microglia but their function in the CNS is poorly understood. CXCR1 and CXCR2 are receptors for ELR-positive CXC chemokines which include growth-regulated oncogene alpha (GRO-alpha) and interleukin-8 (IL-8). GRO-alpha is considered to influence proliferation of cultured oligodendrocyte progenitors (OLPs). Using RT-PCR we show here that the oligodendrocyte precursor cell line CG-4 expresses both CXCR1 and CXCR2. Furthermore we demonstrate that both CG-4 cells and primary cultures of rat OLPs are immunoreactive for CXCR2, the potential receptor for GRO-alpha. This finding demonstrates that the chemokine/chemokine receptor system is probably also involved in the regulation of oligodendroglial cells during developmental processes and may even have implications for inflammatory demyelinating diseases like multiple sclerosis.

Animals↗