Minh Nguyen - Academia.edu (original) (raw)
Papers by Minh Nguyen
Journal of Steroid Biochemistry and Molecular Biology, 2004
Lung maturation before birth includes type II pneumocyte differentiation with progressive disappe... more Lung maturation before birth includes type II pneumocyte differentiation with progressive disappearance of glycogen content and onset of surfactant synthesis.
Heart Lung and Circulation, 2010
Heart, Lung and Circulation Abstracts 2010;19S:S1-S268 death: 10 (38%); median (interquartile ran... more Heart, Lung and Circulation Abstracts 2010;19S:S1-S268 death: 10 (38%); median (interquartile range) PCI door to reperfusion time: 80 (50, 92) min. No predictors for CA death were identified. Age, shock and CA were independent predictors of death for the whole database on LR and CPH. PCI and reperfusion times were not correlates. The CPH hazard ratios (95% confidence interval) were: age 1.11 (1.01, 1.20), shock 98 (95, 100), CA 57 (55, 60). The mortality credible intervals of CA: No PCI 41 (13, 75)%, PCI: 38 (18, 60)%.
Heart Lung and Circulation, 2010
Heart, Lung and Circulation S123 2010;19S:S1-S268 Abstracts
Dynamics of subjective contour and Malach
The eag potas - sium channel binds and locally activates calcium/calmodulin - dependent protein kinase II
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the regulation of n... more Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the regulation of neuronal excitability in many systems. Recent studies suggest that local regulation of membrane potential can have important computational consequences for neuronal function. In Drosophila, CaMKII regulates the eag potassium channel, but if and how this regulation was spatially restricted was unknown. Using coimmunoprecipitation from head extracts and in vitro binding assays, we show that CaMKII and Eag form a stable complex and that association with Eag activates CaMKII independently of CaM and autophosphorylation. Ca(2+)/CaM is necessary to initiate binding of CaMKII to Eag but not to sustain association because binding persists when CaM is removed. The Eag CaMKII-binding domain has homology to the CaMKII autoregulatory region, and the constitutively active CaMKII mutant, T287D, binds Eag Ca(2+)-independently in vitro and in vivo. These results favor a model in which the CaMKII-binding domain of Eag displaces the CaMKII autoinhibitory region. Displacement results in autophosphorylation-independent activation of CaMKII which persists even when Ca(2+) levels have gone down. Activity-dependent binding to this potassium channel substrate allows CaMKII to remain locally active even when Ca(2+) levels have dropped, providing a novel mechanism by which CaMKII can regulate excitability locally over long time scales.
Substance P antagonists: the next breakthrough in treating depression?. REVIEW ARTICLE
Journal of Clinical Pharmacy and Therapeutics, 1999
Several lines of evidence implicate the neuropeptide substance P in depression, either in the pat... more Several lines of evidence implicate the neuropeptide substance P in depression, either in the pathogenesis or as a novel target for amelioration of symptoms. NK1 (substance P) receptor antagonists have been reported to have antidepressant-like actions in animal models. The first clinical trial of an NK1 antagonist showed promising results. A second trial, using a more potent compound, is underway. If the clinical trials show that NK1 (substance P) antagonism represents a well-tolerated, distinct mechanism for antidepressant activity, novel antidepressant agents will emerge as mono- or adjunct-therapy.
Enhanced mast cell activation in mice deficient in the A2b adenosine receptor
Journal of Experimental Medicine, 2007
Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity receptor for IgE ... more Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity receptor for IgE triggers a signaling cascade that results in the release of intracellular calcium stores, followed by an influx of extracellular calcium. The collective increase in intracellular calcium is critical to the release of the granular contents of the mast cell, which include the mediators of acute anaphylaxis. We show that the sensitivity of the mast cell to antigen-mediated degranulation through this pathway can be dramatically influenced by the A2b adenosine receptor. Loss of this Gs-coupled receptor on mouse bone marrow-derived mast cells results in decreased basal levels of cyclic AMP and an excessive influx of extracellular calcium through store-operated calcium channels following antigen activation. Mice lacking the A2b receptor display increased sensitivity to IgE-mediated anaphylaxis. Collectively, these findings show that the A2b adenosine receptor functions as a critical regulator of signaling pathways within the mast cell, which act in concert to limit the magnitude of mast cell responsiveness when antigen is encountered.
Antimicrobial Agents and Chemotherapy, 2010
RDEA806 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with potent in vitro act... more RDEA806 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with potent in vitro activity against wild-type and NNRTI-resistant HIV-1. A phase 2a randomized, double-blind, placebo-controlled, dose-escalating study evaluated the short-term antiviral activity, safety, and pharmacokinetics (PKs) of RDEA806 monotherapy in antiretroviral-naïve, HIV-1-infected subjects. The subjects were randomized to four cohorts comprising four dosage regimens and two formulations of RDEA806 or placebo in a 3:1 ratio within each cohort. The investigators were blinded to the results for each cohort. The subjects received RDEA806 or placebo for 7 days. The primary end point was the change in the HIV RNA load from the baseline to day 9 for each of the four RDEA806 dose regimens compared to that achieved with placebo. The RDEA806 PKs and the immune response to RDEA806 were evaluated along with the safety and tolerability of each dose. Of a total of 48 enrolled subjects, 36 subjects (9 in each cohort) were randomized to RDEA806 study drug, and 12 (3 in each cohort) took placebo. A statistically significant decrease in the viral load from the baseline to day 9 was observed for all RDEA806 treatment groups (P < 0.001). On day 9, the mean changes in the HIV RNA load from that at the baseline were ؊1.95 log 10 copies/ml (400 mg twice a day), ؊1.39 log 10 copies/ml (600 mg once a day [q.d.]), ؊1.62 log 10 copies/ml (800 mg q.d.), and ؊1.70 log 10 copies/ml (1,000 mg q.d.). The pharmacokinetics were linear and dose proportional. Treatment with RDEA806 was well tolerated, and there were no discontinuations due to adverse events. In conclusion, all doses of RDEA806 were safe and well tolerated and exhibited robust antiretroviral activity in this short-term monotherapy study with antiretroviral-naïve HIVinfected subjects. RDEA806 is a potent and promising novel NNRTI.
Journal of General Virology, 2005
Unconventional immune responses have been demonstrated in individuals who, despite repeated expos... more Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus-cell interactions, IgG to CD4-gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4-gp120 complex) were extremely significant predictors of HIV exposure (P<0?0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.
Mammalian Genome, 2002
IGF2 is the major candidate gene for a paternally expressed Quantitative Trait Locus (QTL) in the... more IGF2 is the major candidate gene for a paternally expressed Quantitative Trait Locus (QTL) in the pig primarily aecting muscle development. Here we report two sequence contigs together comprising almost 90 kb containing the INS± IGF2 and H19 genes. A comparative sequence analysis of the pig, human, and mouse genomic sequences was conducted to identify the exon/intron organization, all promoters, and other evolutionarily conserved elements. RT-PCR analysis showed that IGF2 transcripts originated from four dierent promoters and included various combinations of seven untranslated exons together with three coding exons, in agreement with previous ®ndings in other mammals. The observed sequence similarity in intronic and intragenic regions among the three species is remarkable and is most likely explained by the complicated regulation of imprinting and expression of these genes. The general trend was, as expected, a higher sequence similarity between human and pig than between these species and the mouse, but a few exceptions to this rule were noted. This genomic region exhibits several striking features, including a very high GC content, many CpG islands, and a low amount of interspersed repeats. The high GC and CpG content were more pronounced in the pig than in the two other species. The results will facilitate the further characterization of this important QTL in the pig.
Regulatory Peptides, 2004
Previous modeling (PDB 1cfk) of the catecholamine release-inhibitory “catestatin” region of chrom... more Previous modeling (PDB 1cfk) of the catecholamine release-inhibitory “catestatin” region of chromogranin A (CgA) suggested a β-strand/loop/β-strand active conformation, displaying an electropositive Arg-rich loop (R351AR353GYGFR358). To explore this possibility, we studied NMR structures of linear and cyclic synthetic catestatin, bovine (bCgA344–364) or human (hCgA352–372). By 2-D 1H-NMR, the structure of linear catestatin (hCgA352–372) exhibited the NOE pattern of a coiled loop (PDB 1lv4). We then constrained the structure, cyclizing the putative Arg-rich loop connecting the β-strands: cyclic bCgA350–362 ([C0]F350RARGYGFRGPGL362[C+14]). Favored conformations of cyclic bCgA350–362 were determined by 1H-NMR and 13C-NMR spectroscopy. Cyclic bCgA350–362 conformers (PDB 1n2y) adopted a “twisted-loop” conformation. Alignment between the homology model and the cyclic NMR structure showed that, while portions of the NMR structure's mid-molecule and carboxy-terminus were congruent with the homology model (RMSD, 1.61–1.91 Å), the amino-terminal “twisted loop” coiled inward and away from the model (RMSD, 3.36 Å). Constrained cyclic bCgA350–362 did not exert nicotinic cholinergic antagonist activity (IC50>10 μM), when compared to full-length linear (IC50∼0.42–0.56 μM), or cyclic (IC50∼0.74 μM) catestatin. Thus, loss of activity in the small, constrained peptide did not result from either [Cys]-extension or cyclization, per se. While linear catestatin displays coiled character, a small cyclic derivative lost biological activity, perhaps because its amino-terminal domain deviated sharply from the predicted active conformation. These results refine the relationship between structure and function in catestatin, and suggest goals in future peptidomimetic syntheses, in particular attempts to constrain the correct amino-terminal shape for biological activity.
We characterized 18 genes from Caenorhabditis elegans that, when mutated, confer recessive resist... more We characterized 18 genes from Caenorhabditis elegans that, when mutated, confer recessive resistance to inhibitors of acetylcholinesterase. These include previously described genes as well as newly identified genes; they encode essential as well as nonessential functions. In the absence of acetylcholinesterase inhibitors, the different mutants display a wide range of behavioral deficits, from mild uncoordination to almost complete paralysis. Measurements of acetylcholine levels in these mutants suggest that some of the genes are involved in presynaptic functions Corresponding 'These studies were begun while A.A, C.DJ., and J.B.R. were affiliated with the Department of Zoology, University of Wisconsin-Madison.
Alpha7 nicotinic receptor subunits are not necessary for hippocampal - dependent learning or sensorimotor gating: a behavioral characterization of Acra7 - deficient mice
The alpha7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippoc... more The alpha7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of alpha7 nAChR and in sensorimotor gating impairments. To examine the role of alpha7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally, Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of alpha7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of alpha7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments.
Revue Du Rhumatisme, 2009
Prévalence et évaluation de l'impact du psoriasis sur l'évolution naturelle de la coxarthrose. Ré... more Prévalence et évaluation de l'impact du psoriasis sur l'évolution naturelle de la coxarthrose. Résultats d'un suivi sur dix ans de 507 patients (étude Echodiah) ଝ Self-reported prevalence of psoriasis and evaluation of the impact on the natural history of hip osteoarthritis. Results of a 10 years follow-up study of 507 patients (Echodiah study) Accepté le 10 octobre 2008 Disponible sur Internet le 21 juin 2009
Immuno-analyse & Biologie Specialisee, 2002
International Journal of Radiation Oncology Biology Physics, 2005
Purpose/Objective: Three-dimensional external beam radiation therapy has been used for patients w... more Purpose/Objective: Three-dimensional external beam radiation therapy has been used for patients with unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC) with encouraging results. Prospective studies have demonstrated that doses of 48 -72.6 Gy (fraction size 1.5-1.65 Gy bid) can be given, achieving hepatic control rates of 50%. In addition, 3-dimensional treatment planning for liver metastases has allowed the safe irradiation of 2/3 of the normal liver to 48 -52.4 Gy and 1/3 of the liver to 66 -72.6 Gy (fraction size 1.5-1.65 Gy bid).
International Journal of Biochemistry & Cell Biology, 2000
Gelatinase A, a member of the matrix metalloproteinase (MMP) family, plays an important role duri... more Gelatinase A, a member of the matrix metalloproteinase (MMP) family, plays an important role during angiogenesis. It is constitutively expressed by human endothelial cells as a latent enzyme and requires activation. Thrombin is the only described physiological inducer of gelatinase A in human endothelial cells. In this study, we investigated the mechanisms of gelatinase A activation by another physiological inducer, collagen. Endothelial cells were cultured on various ECM components for 24 h and the conditioned media were assessed for gelatinase A activity using gelatin zymography. The results demonstrated that type I collagen matrix specifically activates gelatinase A after 24 h in human umbilical vein and 48 h in neonatal foreskin endothelial cells. In contrast, thrombin activated gelatinase A after only 2 h. Activation by collagen was sustained over long periods of time in culture (96 h). Unlike thrombin-induced activation, collagen required active membrane type 1-MMP (MT1-MMP) on the endothelial cell surface to activate gelatinase A. In addition, collagen-induced activation of gelatinase A was inhibited by antibodies to the integrin receptor, α2β1, but not α3β1. Our findings, that collagen can provide long-term activation of gelatinase A are likely to be relevant to endothelial cell invasion during angiogenesis.
A Nationally-Representative Epidemiological and Risk Factor Assessment of Child Mental Health in Vietnam
International perspectives in psychology : research, practice, consultation, 2014
As part of the global mental health…
Cancer immunology, immunotherapy : CII, 2010
A critical factor in clinical development of cancer immunotherapies is the identification of tumo... more A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing [8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte-macrophage colony-stimulating factor (GM-CSF)secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P B 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.
Order Book Commonalities and Bond Return Predictability
SSRN Electronic Journal, 2000
Page 1. Electronic copy available at: http://ssrn.com/abstract=1664945 Order Book Commonalities a... more Page 1. Electronic copy available at: http://ssrn.com/abstract=1664945 Order Book Commonalities and Bond Return Predictability Alfonso Dufour 1 and Minh Nguyen 2 3 June 15, 2010 1ICMA Centre, Henley Business School ...
Journal of Steroid Biochemistry and Molecular Biology, 2004
Lung maturation before birth includes type II pneumocyte differentiation with progressive disappe... more Lung maturation before birth includes type II pneumocyte differentiation with progressive disappearance of glycogen content and onset of surfactant synthesis.
Heart Lung and Circulation, 2010
Heart, Lung and Circulation Abstracts 2010;19S:S1-S268 death: 10 (38%); median (interquartile ran... more Heart, Lung and Circulation Abstracts 2010;19S:S1-S268 death: 10 (38%); median (interquartile range) PCI door to reperfusion time: 80 (50, 92) min. No predictors for CA death were identified. Age, shock and CA were independent predictors of death for the whole database on LR and CPH. PCI and reperfusion times were not correlates. The CPH hazard ratios (95% confidence interval) were: age 1.11 (1.01, 1.20), shock 98 (95, 100), CA 57 (55, 60). The mortality credible intervals of CA: No PCI 41 (13, 75)%, PCI: 38 (18, 60)%.
Heart Lung and Circulation, 2010
Heart, Lung and Circulation S123 2010;19S:S1-S268 Abstracts
Dynamics of subjective contour and Malach
The eag potas - sium channel binds and locally activates calcium/calmodulin - dependent protein kinase II
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the regulation of n... more Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the regulation of neuronal excitability in many systems. Recent studies suggest that local regulation of membrane potential can have important computational consequences for neuronal function. In Drosophila, CaMKII regulates the eag potassium channel, but if and how this regulation was spatially restricted was unknown. Using coimmunoprecipitation from head extracts and in vitro binding assays, we show that CaMKII and Eag form a stable complex and that association with Eag activates CaMKII independently of CaM and autophosphorylation. Ca(2+)/CaM is necessary to initiate binding of CaMKII to Eag but not to sustain association because binding persists when CaM is removed. The Eag CaMKII-binding domain has homology to the CaMKII autoregulatory region, and the constitutively active CaMKII mutant, T287D, binds Eag Ca(2+)-independently in vitro and in vivo. These results favor a model in which the CaMKII-binding domain of Eag displaces the CaMKII autoinhibitory region. Displacement results in autophosphorylation-independent activation of CaMKII which persists even when Ca(2+) levels have gone down. Activity-dependent binding to this potassium channel substrate allows CaMKII to remain locally active even when Ca(2+) levels have dropped, providing a novel mechanism by which CaMKII can regulate excitability locally over long time scales.
Substance P antagonists: the next breakthrough in treating depression?. REVIEW ARTICLE
Journal of Clinical Pharmacy and Therapeutics, 1999
Several lines of evidence implicate the neuropeptide substance P in depression, either in the pat... more Several lines of evidence implicate the neuropeptide substance P in depression, either in the pathogenesis or as a novel target for amelioration of symptoms. NK1 (substance P) receptor antagonists have been reported to have antidepressant-like actions in animal models. The first clinical trial of an NK1 antagonist showed promising results. A second trial, using a more potent compound, is underway. If the clinical trials show that NK1 (substance P) antagonism represents a well-tolerated, distinct mechanism for antidepressant activity, novel antidepressant agents will emerge as mono- or adjunct-therapy.
Enhanced mast cell activation in mice deficient in the A2b adenosine receptor
Journal of Experimental Medicine, 2007
Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity receptor for IgE ... more Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity receptor for IgE triggers a signaling cascade that results in the release of intracellular calcium stores, followed by an influx of extracellular calcium. The collective increase in intracellular calcium is critical to the release of the granular contents of the mast cell, which include the mediators of acute anaphylaxis. We show that the sensitivity of the mast cell to antigen-mediated degranulation through this pathway can be dramatically influenced by the A2b adenosine receptor. Loss of this Gs-coupled receptor on mouse bone marrow-derived mast cells results in decreased basal levels of cyclic AMP and an excessive influx of extracellular calcium through store-operated calcium channels following antigen activation. Mice lacking the A2b receptor display increased sensitivity to IgE-mediated anaphylaxis. Collectively, these findings show that the A2b adenosine receptor functions as a critical regulator of signaling pathways within the mast cell, which act in concert to limit the magnitude of mast cell responsiveness when antigen is encountered.
Antimicrobial Agents and Chemotherapy, 2010
RDEA806 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with potent in vitro act... more RDEA806 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with potent in vitro activity against wild-type and NNRTI-resistant HIV-1. A phase 2a randomized, double-blind, placebo-controlled, dose-escalating study evaluated the short-term antiviral activity, safety, and pharmacokinetics (PKs) of RDEA806 monotherapy in antiretroviral-naïve, HIV-1-infected subjects. The subjects were randomized to four cohorts comprising four dosage regimens and two formulations of RDEA806 or placebo in a 3:1 ratio within each cohort. The investigators were blinded to the results for each cohort. The subjects received RDEA806 or placebo for 7 days. The primary end point was the change in the HIV RNA load from the baseline to day 9 for each of the four RDEA806 dose regimens compared to that achieved with placebo. The RDEA806 PKs and the immune response to RDEA806 were evaluated along with the safety and tolerability of each dose. Of a total of 48 enrolled subjects, 36 subjects (9 in each cohort) were randomized to RDEA806 study drug, and 12 (3 in each cohort) took placebo. A statistically significant decrease in the viral load from the baseline to day 9 was observed for all RDEA806 treatment groups (P < 0.001). On day 9, the mean changes in the HIV RNA load from that at the baseline were ؊1.95 log 10 copies/ml (400 mg twice a day), ؊1.39 log 10 copies/ml (600 mg once a day [q.d.]), ؊1.62 log 10 copies/ml (800 mg q.d.), and ؊1.70 log 10 copies/ml (1,000 mg q.d.). The pharmacokinetics were linear and dose proportional. Treatment with RDEA806 was well tolerated, and there were no discontinuations due to adverse events. In conclusion, all doses of RDEA806 were safe and well tolerated and exhibited robust antiretroviral activity in this short-term monotherapy study with antiretroviral-naïve HIVinfected subjects. RDEA806 is a potent and promising novel NNRTI.
Journal of General Virology, 2005
Unconventional immune responses have been demonstrated in individuals who, despite repeated expos... more Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus-cell interactions, IgG to CD4-gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4-gp120 complex) were extremely significant predictors of HIV exposure (P<0?0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.
Mammalian Genome, 2002
IGF2 is the major candidate gene for a paternally expressed Quantitative Trait Locus (QTL) in the... more IGF2 is the major candidate gene for a paternally expressed Quantitative Trait Locus (QTL) in the pig primarily aecting muscle development. Here we report two sequence contigs together comprising almost 90 kb containing the INS± IGF2 and H19 genes. A comparative sequence analysis of the pig, human, and mouse genomic sequences was conducted to identify the exon/intron organization, all promoters, and other evolutionarily conserved elements. RT-PCR analysis showed that IGF2 transcripts originated from four dierent promoters and included various combinations of seven untranslated exons together with three coding exons, in agreement with previous ®ndings in other mammals. The observed sequence similarity in intronic and intragenic regions among the three species is remarkable and is most likely explained by the complicated regulation of imprinting and expression of these genes. The general trend was, as expected, a higher sequence similarity between human and pig than between these species and the mouse, but a few exceptions to this rule were noted. This genomic region exhibits several striking features, including a very high GC content, many CpG islands, and a low amount of interspersed repeats. The high GC and CpG content were more pronounced in the pig than in the two other species. The results will facilitate the further characterization of this important QTL in the pig.
Regulatory Peptides, 2004
Previous modeling (PDB 1cfk) of the catecholamine release-inhibitory “catestatin” region of chrom... more Previous modeling (PDB 1cfk) of the catecholamine release-inhibitory “catestatin” region of chromogranin A (CgA) suggested a β-strand/loop/β-strand active conformation, displaying an electropositive Arg-rich loop (R351AR353GYGFR358). To explore this possibility, we studied NMR structures of linear and cyclic synthetic catestatin, bovine (bCgA344–364) or human (hCgA352–372). By 2-D 1H-NMR, the structure of linear catestatin (hCgA352–372) exhibited the NOE pattern of a coiled loop (PDB 1lv4). We then constrained the structure, cyclizing the putative Arg-rich loop connecting the β-strands: cyclic bCgA350–362 ([C0]F350RARGYGFRGPGL362[C+14]). Favored conformations of cyclic bCgA350–362 were determined by 1H-NMR and 13C-NMR spectroscopy. Cyclic bCgA350–362 conformers (PDB 1n2y) adopted a “twisted-loop” conformation. Alignment between the homology model and the cyclic NMR structure showed that, while portions of the NMR structure's mid-molecule and carboxy-terminus were congruent with the homology model (RMSD, 1.61–1.91 Å), the amino-terminal “twisted loop” coiled inward and away from the model (RMSD, 3.36 Å). Constrained cyclic bCgA350–362 did not exert nicotinic cholinergic antagonist activity (IC50>10 μM), when compared to full-length linear (IC50∼0.42–0.56 μM), or cyclic (IC50∼0.74 μM) catestatin. Thus, loss of activity in the small, constrained peptide did not result from either [Cys]-extension or cyclization, per se. While linear catestatin displays coiled character, a small cyclic derivative lost biological activity, perhaps because its amino-terminal domain deviated sharply from the predicted active conformation. These results refine the relationship between structure and function in catestatin, and suggest goals in future peptidomimetic syntheses, in particular attempts to constrain the correct amino-terminal shape for biological activity.
We characterized 18 genes from Caenorhabditis elegans that, when mutated, confer recessive resist... more We characterized 18 genes from Caenorhabditis elegans that, when mutated, confer recessive resistance to inhibitors of acetylcholinesterase. These include previously described genes as well as newly identified genes; they encode essential as well as nonessential functions. In the absence of acetylcholinesterase inhibitors, the different mutants display a wide range of behavioral deficits, from mild uncoordination to almost complete paralysis. Measurements of acetylcholine levels in these mutants suggest that some of the genes are involved in presynaptic functions Corresponding 'These studies were begun while A.A, C.DJ., and J.B.R. were affiliated with the Department of Zoology, University of Wisconsin-Madison.
Alpha7 nicotinic receptor subunits are not necessary for hippocampal - dependent learning or sensorimotor gating: a behavioral characterization of Acra7 - deficient mice
The alpha7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippoc... more The alpha7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of alpha7 nAChR and in sensorimotor gating impairments. To examine the role of alpha7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally, Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of alpha7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of alpha7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments.
Revue Du Rhumatisme, 2009
Prévalence et évaluation de l'impact du psoriasis sur l'évolution naturelle de la coxarthrose. Ré... more Prévalence et évaluation de l'impact du psoriasis sur l'évolution naturelle de la coxarthrose. Résultats d'un suivi sur dix ans de 507 patients (étude Echodiah) ଝ Self-reported prevalence of psoriasis and evaluation of the impact on the natural history of hip osteoarthritis. Results of a 10 years follow-up study of 507 patients (Echodiah study) Accepté le 10 octobre 2008 Disponible sur Internet le 21 juin 2009
Immuno-analyse & Biologie Specialisee, 2002
International Journal of Radiation Oncology Biology Physics, 2005
Purpose/Objective: Three-dimensional external beam radiation therapy has been used for patients w... more Purpose/Objective: Three-dimensional external beam radiation therapy has been used for patients with unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC) with encouraging results. Prospective studies have demonstrated that doses of 48 -72.6 Gy (fraction size 1.5-1.65 Gy bid) can be given, achieving hepatic control rates of 50%. In addition, 3-dimensional treatment planning for liver metastases has allowed the safe irradiation of 2/3 of the normal liver to 48 -52.4 Gy and 1/3 of the liver to 66 -72.6 Gy (fraction size 1.5-1.65 Gy bid).
International Journal of Biochemistry & Cell Biology, 2000
Gelatinase A, a member of the matrix metalloproteinase (MMP) family, plays an important role duri... more Gelatinase A, a member of the matrix metalloproteinase (MMP) family, plays an important role during angiogenesis. It is constitutively expressed by human endothelial cells as a latent enzyme and requires activation. Thrombin is the only described physiological inducer of gelatinase A in human endothelial cells. In this study, we investigated the mechanisms of gelatinase A activation by another physiological inducer, collagen. Endothelial cells were cultured on various ECM components for 24 h and the conditioned media were assessed for gelatinase A activity using gelatin zymography. The results demonstrated that type I collagen matrix specifically activates gelatinase A after 24 h in human umbilical vein and 48 h in neonatal foreskin endothelial cells. In contrast, thrombin activated gelatinase A after only 2 h. Activation by collagen was sustained over long periods of time in culture (96 h). Unlike thrombin-induced activation, collagen required active membrane type 1-MMP (MT1-MMP) on the endothelial cell surface to activate gelatinase A. In addition, collagen-induced activation of gelatinase A was inhibited by antibodies to the integrin receptor, α2β1, but not α3β1. Our findings, that collagen can provide long-term activation of gelatinase A are likely to be relevant to endothelial cell invasion during angiogenesis.
A Nationally-Representative Epidemiological and Risk Factor Assessment of Child Mental Health in Vietnam
International perspectives in psychology : research, practice, consultation, 2014
As part of the global mental health…
Cancer immunology, immunotherapy : CII, 2010
A critical factor in clinical development of cancer immunotherapies is the identification of tumo... more A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing [8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte-macrophage colony-stimulating factor (GM-CSF)secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P B 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.
Order Book Commonalities and Bond Return Predictability
SSRN Electronic Journal, 2000
Page 1. Electronic copy available at: http://ssrn.com/abstract=1664945 Order Book Commonalities a... more Page 1. Electronic copy available at: http://ssrn.com/abstract=1664945 Order Book Commonalities and Bond Return Predictability Alfonso Dufour 1 and Minh Nguyen 2 3 June 15, 2010 1ICMA Centre, Henley Business School ...