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Biomedical subjects

T D Nguyen

Publications and source records attributed to T D Nguyen.

At least 19 recordsLinked to original sources

Comparative analytical sensitivities of six rapid influenza A antigen detection test kits for detection of influenza A subtypes H1N1, H3N2 and H5N1.

BACKGROUND: Rapid and simple methods for diagnosing human influenza A (H5N1) disease urgently needed. The limited data so far suggest that the currently available rapid antigen detection kits have poor clinical sensitivity for diagnosis of human H5N1 disease. OBJECTIVES: To compare the analytical sensitivity of six commercially available rapid antigen detection kits for the detection of "human" (subtypes H1N1, H3N2) and "avian" (subtype H5N1) influenza A viruses. STUDY DESIGN: Six commercially available test kits for the detection of influenza A were investigated. Analytic sensitivity for the detection of two contemporary H1N1, two H3N2 and three H5N1 viruses was determined using virus culture as a reference method. RESULTS AND CONCLUSIONS: Each test kit detected the H5N1 virus subtypes as efficiently as they detected conventional human viruses of subtypes H1N1 or H3N2. However, limits of detection of influenza viruses of all subtypes by antigen detection kits were >1000-fold lower than virus isolation. Thus, the reportedly poor clinical sensitivity of these antigen detection kits for diagnosis of patients with H5N1 disease is not due to a difference of sensitivity for detecting avian influenza H5N1 compared to human influenza viruses.

Animals↗

Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam.

Highly pathogenic avian influenza virus H5N1 is endemic in poultry in East and Southeast Asia with disease outbreaks recently spreading to parts of central Asia, Europe and Africa. Continued interspecies transmission to humans has been reported in Vietnam, Thailand, Cambodia, Indonesia and China, causing pandemic concern. Here, we genetically characterize 82 H5N1 viruses isolated from poultry throughout Indonesia and Vietnam and 11 human isolates from southern Vietnam together with sequence data available in public databases to address questions relevant to virus introduction, endemicity and evolution. Phylogenetic analysis shows that all viruses from Indonesia form a distinct sublineage of H5N1 genotype Z viruses suggesting this outbreak likely originated from a single introduction that spread throughout the country during the past two years. Continued virus activities in Indonesia were attributed to transmission via poultry movement within the country rather than through repeated introductions by bird migration. Within Indonesia and Vietnam, H5N1 viruses have evolved over time into geographically distinct groups within each country. Molecular analysis of the H5N1 genotype Z genome shows that only the M2 and PB1-F2 genes were under positive selection, suggesting that these genes might be involved in adaptation of this virus to new hosts following interspecies transmission. At the amino acid level 12 residues were under positive selection in those genotype Z viruses, in the HA and PB1-F2 proteins. Some of these residues were more frequently observed in human isolates than in avian isolates and are related to viral antigenicity and receptor binding. Our study provides insight into the ongoing evolution of H5N1 influenza viruses that are transmitting in diverse avian species and at the interface between avian and human hosts.

Animals↗

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control.

Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.

Animals↗

The contribution of germline rearrangements to the spectrum of BRCA2 mutations.

BACKGROUND: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. OBJECTIVE: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.

Exons↗

[Postoperative radiotherapy in N0 laryngeal cancer].

PURPOSE: A retrospective study to re-assess the indications for postoperative radiation therapy in squamous cell carcinoma of the larynx staged N0 after gross resection. PATIENTS AND METHODS: Between January 1975 and December 2000, 166 patients with squamous cell carcinoma of the larynx were treated by total laryngectomy with or without neck dissection. Surgery was completed by external radiotherapy delivering 45 to 65 Gy to the tumour bed and 45 to 50 Gy to cervical lymphatic chains. Minimal follow-up was 36 months and median follow-up was 98 months. RESULTS: The rate of nodal recurrence was 6% (median time for relapse was 9 months). The survival rates at 1, 2, 3 and 5 years were 93.5, 84, 80 and 69% respectively, with a 8 year 3 month median survival. The univariate analysis showed 4 parameters, which significantly increased the risk of local recurrence: the medical necessity for immediate tracheotomy, the subglottic involvement, the involvement of the whole larynx and the presence of lymphatic embols in the neck dissection. There was no statistically significant difference between the patients with or without a neck dissection. Fifty-nine secondary cancers were observed, 15 of them occurring in the head and neck area. The late complications consisted of cervical subcutaneous fibrosis (7%), oesophageal stricture (4%), oeso-tracheal fistula (l%), hypothyroidism (3%), bone necrosis (1%). CONCLUSION: Prophylactic cervical radiotherapy in laryngeal cancers resulted in 6% cervical node recurrence rate. This value may represent the maximal rate to accept if one would favour new therapeutic strategies based on restricted indications for radiotherapy.

Adult↗

Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia.

Wild waterfowl, including ducks, are natural hosts of influenza A viruses. These viruses rarely caused disease in ducks until 2002, when some H5N1 strains became highly pathogenic. Here we show that these H5N1 viruses are reverting to nonpathogenicity in ducks. Ducks experimentally infected with viruses isolated between 2003 and 2004 shed virus for an extended time (up to 17 days), during which variant viruses with low pathogenicity were selected. These results suggest that the duck has become the "Trojan horse" of Asian H5N1 influenza viruses. The ducks that are unaffected by infection with these viruses continue to circulate these viruses, presenting a pandemic threat.

Animals↗

Are ducks contributing to the endemicity of highly pathogenic H5N1 influenza virus in Asia?

Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1 outbreaks in Asia have resulted in mortality among waterfowl in recreational parks, domestic flocks, and wild migratory birds. The evolutionary stasis between influenza virus and its natural host may have been disrupted, prompting us to ask whether waterfowl are resistant to H5N1 influenza virus disease and whether they can still act as a reservoir for these viruses. To better understand the biology of H5N1 viruses in ducks and attempt to answer this question, we inoculated juvenile mallards with 23 different H5N1 influenza viruses isolated in Asia between 2003 and 2004. All virus isolates replicated efficiently in inoculated ducks, and 22 were transmitted to susceptible contacts. Viruses replicated to higher levels in the trachea than in the cloaca of both inoculated and contact birds, suggesting that the digestive tract is not the main site of H5N1 influenza virus replication in ducks and that the fecal-oral route may no longer be the main transmission path. The virus isolates' pathogenicities varied from completely nonpathogenic to highly lethal and were positively correlated with tracheal virus titers. Nevertheless, the eight virus isolates that were nonpathogenic in ducks replicated and transmitted efficiently to naïve contacts, suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease in ducks can propagate silently and efficiently among domestic and wild ducks in Asia and that they represent a serious threat to human and veterinary public health.

Animals↗

Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia.

A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2-4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.

Animals↗

Virulent Toxoplasma gondii strain RH promotes T-cell-independent overproduction of proinflammatory cytokines IL12 and gamma-interferon.

The aim of this study was the analysis of the cytokine response in BALB/c mice infected with the highly virulent RH or the weakly virulent Beverley strains of Toxoplasma gondii. Analysis of cytokine messages showed increased expression of IL12, IFN-gamma and TNF-alpha, but not IL4 mRNAs in spleen cells after infection with the T. gondii strains RH and Beverley. High levels of circulating IL12 and IFN-gamma were detected in the serum of mice infected with strain RH, although TNF-alpha levels remained low. In contrast, the same cytokines were detected at only low levels in the serum of mice infected with the Beverley strain. Administration of antibody against IL12 or IFN-gamma significantly delayed time to death of mice infected with strain RH compared to controls. T-Cell-deficient as well as normal mice were equally infected by strain RH, suggesting that T lymphocytes do not contribute to the response. Depletion of natural killer cells from the splenocyte population abolished the in vitro production of IFN-gamma. Together, our data suggest that the virulent strain RH induces in BALB/c mice a type 1 cytokine pattern with T-cell-independent overproduction of IL12 and IFN-gamma that may be involved in the pathogenesis of this micro-organism.

Animals↗

Regional frequency analysis of extreme rainfalls.

This study proposes two alternative methods for estimating the distribution of extreme rainfalls for sites where rainfall data are available (gaged sites) and for locations without data (ungaged sites). The first method deals with the estimation of short-duration rainfall extremes from available rainfall data for longer durations using the "scale-invariance" concept to account for the relationship between statistical properties of extreme rainfall processes for different time scales. The second method is concerned with the estimation of extreme rainfalls for ungaged sites. This method relies on a new definition of homogeneous sites. Results of the numerical application using data from a network of 10 recording rain gauges in Quebec (Canada) indicate that the proposed methods are able to provide extreme rainfall estimates that are comparable with those based on observed at-site rainfall data.

Calibration↗

Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors.

Tumor promoters are non-mutagenic chemicals which increase the probability of cancer by accelerating the clonal expansion of cells transformed during tumor initiation. Phenobarbital (PB) is an antiepileptic drug which promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like diethylnitrosamine (DEN). Here we have investigated the prevalence and patterns of mutations in two genes, Ha-ras and beta-catenin, both known mutational targets in mouse hepatocarcinogenesis. Liver tumors were generated by a single administration of DEN to 6 week old mice followed by feeding of PB (0.05%) containing or control diet for 39 weeks. Mutations at Ha-ras codon 61 were screened by allele-specific oligonucleotide hybridization; beta-catenin mutations were detected by direct sequencing of PCR products spanning exon 2. In tumors from mice treated with DEN alone, the prevalence of Ha-ras mutations was approximately 30% (6/20), while no beta-catenin mutations (0/13) were detectable in tumors of this treatment group. By contrast, Ha-ras mutations were undetectable in tumors from mice treated with DEN/PB (0/32), while approximately 80% (37/46) of tumors from this group showed beta-catenin mutations. These results demonstrate that PB strongly affects the prevalence of mutations in the two cancer-related genes, presumably by positive and negative selection for cells harboring the respective mutation.

Animals↗

Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages.

Focal cerebral ischemia elicits a strong inflammatory response which readily participates in lipid oxygenation, edema formation, apoptotic cell death and tissue remodeling. Within these conditions, cytokines are key players of cell activation and are crucial for delayed mechanisms of ischemic damage. Mature IL-16 is an immunomodulatory cytokine, exerting CD4 dependent and independent effects and is characterized by chemotactic activity, induction of early gene phosphorylation, stimulation of pro-inflammatory IL-1beta, IL-6, TNFalpha expression in monocytic cells and also modulates apoptosis. We have now analyzed expression of IL-16 in 20 brains of patients following focal cerebral infarctions (FCI, n=20). Compared to normal control brains (n=3), IL-16 was expressed by infiltrating immune cells such as neutrophils, CD8+ lymphocytes and activated CD68+ microglia/macrophages accumulating in lesion associated reactive zones and in peri-vascular regions. IL-16+ cells accumulated significantly (P<0.0001) in the necrotic lesion and at bordering peri-lesional areas at day 1-2 reaching maximum levels at day 3-4 (P<0.0001). Also, peri-vascular IL-16+ cells reached maximum levels at day 3-4 (P<0.0001) following infarction and decreased after several weeks. During the early microglial activation period, IL-16+ microglia/macrophages coexpress the activation antigen MRP-8. The accumulation of IL-16+ granulocytes, IL-16+, CD8+ lymphocytes and activated IL-16+, CD68+, CD4- microglia/macrophages, early after infarction suggest a CD4 independent, paracrine role of IL-16 in the postinjury inflammatory response, such as recruitment and activation of immune cells leading to microvessel clustering and blood-brain barrier disturbance resulting in secondary damage.

Aged↗

k-Space weighted least-squares algorithm for accurate and fast motion extraction from magnetic resonance navigator echoes.

Navigator echoes provide an effective method to monitor physiological motion, allowing motion artifacts to be suppressed by modifying the data acquisition accordingly. The displacement can be measured directly from the navigator phase using an algorithm suggested by Ahn and Cho (IEEE Trans Med Imaging 1987;MI-6:32-36). Although computationally efficient, it is susceptible to noise, particularly contributions from points at the edges of k-space. A k-space weighted least-squares (kLS) algorithm is proposed which fits a straight line to the motion-induced phase shift. The linear fit is weighted strongly to high SNR points near the k-space center and only weakly to the poor SNR points at the edges of k-space. This algorithm was found to be as efficient as Ahn's algorithm but more robust against noise.

Algorithms↗

Differential activation of microglial cells in local and remote areas of IRBP1169-1191-induced rat uveitis.

Using a Lewis rat model of interphotoreceptor retinoid binding protein (IRBP)-induced experimental autoimmune uveitis (EAU) we examined cellular reactions in the optic pathway (retina, choroid, optic nerve, optic tract, colliculus superior, and visual cortex). Two to six animals were studied at days 0, 7, 9, 11, 12, 13, 14, 18 and 22 after immunization by immunohistochemistry with monoclonal antibodies against ED , ED2, OX6, OX22, EMAP II, AIF-1 and W3/13. In the retina, choroid and distal optic nerve increased immunoreactivity to ED1, OX6, OX22, EMAP II, AIF-1 and W3/13 was initially observed at day 9, peaked at days 13-14 and diminished rapidly from day 18 onwards. No changes were seen in the density of ED2-positive resident macrophages. In the optic tract, ED1 and OX6 expression was induced in microglial cells beginning with day 11 and persisted until day 22. AIF-1, EMAP II and ED2 expression was not visibly up-regulated and no lymphocytic infiltrates (OX22-, W3/13-positive cells) were observed. In the central projection fields, no cellular reaction could be found. Thus, cellular response in IRBP-induced rat uveoretinitis is not restricted to the eye. Microglial activation is also seen in the distal optic nerve and optic tract. This remote microglial activation, however, differs in intensity, time course and expression of activation markers, thus indicating different activation cascades. The mild remote microglial activation is probably due to neuronal-microglial interactions resulting from neuronal damage in the retinal ganglion cell layer and nerve fiber layer with consecutive axonal degeneration and not from an inflammatory reaction as seen in the eye.

Animals↗

Optimization of view ordering for motion artifact suppression.

Motion artifacts in MRI may be reduced by optimized view ordering. Extensive simulations of view-ordering techniques were performed on high-resolution phantom images to determine the best strategy for distributing motion in k-space. Although not exhaustive, simulation results indicate that minimizing motion at the center of k-space is critical to overall image quality. For 2D imaging, using edge-center-edge view order and setting the readout direction parallel to the direction of the motion produces the sharpest point spread function and the lowest image energy error. For 3D imaging, using an edge-center-edge view order proves to be the optimum choice in general. Given these observations, several important issues regarding the measurement of motion effects are discussed.

Algorithms↗

Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a highly prevalent optic neuropathy and a major cause of irreversible blindness, with elevation of intraocular pressure (IOP) being a primary risk factor. The trabecular meshwork-inducible glucocorticoid response (TIGR)/MYOCILIN (MYOC) gene coding region is mutated in 3-4% of POAG patients. Here, in a retrospective study of 142 POAG patients, we evaluated the influence on glaucoma phenotype of a novel biallelic polymorphism (-1000C/G) located in the upstream region of the MYOC gene. Allele frequencies were similar among patients and controls. However, the G allele (frequency 17.6%), also designated as MYOC.mt1, was associated with an increased IOP (+4.9 mmHg, p=0.0004) and a more damaged visual field (p=0.02). Both effects were predominant in females. Moreover, whereas IOP in MYOC.mt1 noncarriers decreased very markedly to the normal range between diagnosis and inclusion in the study (p=3 x 10(-5) in both males and females), reflecting successful therapy, it decreased less noticeably in MYOC.mt1+ male patients (p=0.005) and not at all in MYOC.mt1+ female patients. MYOC.mt1 appears therefore to be an indicator of poor IOP control and greater visual field damage in diagnosed POAG patients, potentially due to a lack of response to therapeutic intervention. Its typing might help in the selection of treatment paradigms for the management of POAG patients.

Alleles↗

Posterior petrous face meningiomas.

OBJECTIVE: To define the clinical presentation, treatment options, and outcomes for a subset of meningiomas of the posterior fossa skull base that arise from the posterior petrous face between the region of the porus acousticus and the sigmoid sinus. STUDY DESIGN AND SETTING: A retrospective chart review from a large skull base surgery practice at a tertiary care institution. RESULTS: This cohort of patients presented with minimal symptoms, yet large tumors, averaging 3.8 cms and causing significant cerebellar compression. Retrosigmoid craniotomies afforded excellent exposure. CONCLUSION AND SIGNIFICANCE: Patients with large tumors emanating from the posterior fossa aspect of the temporal bone should be evaluated on the basis of their site of origin. Patients with tumors emanating from the anterior or ventral portion of the temporal bone have greater symptoms and greater operative complications than those emanating from the posterior petrous face, between the porus acousticus and sigmoid sinus.

Adult↗