Browse Health
Radiologist
19 years of experience

Education ?

Medical School Score
The University of Texas at Galveston (1991)
  • Currently 2 of 4 apples

Awards & Distinctions ?

Associations
American Board of Radiology

Affiliations ?

Dr. Nguyen is affiliated with 6 hospitals.

Hospital Affilations

Score

Rankings

  • Harris Methodist H E B
    1600 Hospital Pkwy, Bedford, TX 76022
    • Currently 4 of 4 crosses
    Top 25%
  • Medical Center Of Plano
    3901 W 15th St, Plano, TX 75075
    • Currently 2 of 4 crosses
  • St. Mary Medical Center
  • Texas Health Fort Worth
  • Pacific Hospital of Long Beach
  • Long Beach Memorial Medical Center
  • Publications & Research

    Dr. Nguyen has contributed to 55 publications.
    Title Vascular Endothelial Growth Factor and Platelet Derived Growth Factor Modulates the Glial Response to a Cortical Stab Injury.
    Date January 2012
    Journal Neuroscience
    Excerpt

    Traumatic injury to the brain initiates an increase in astrocyte and microglial infiltration as part of an inflammatory response to injury. Increased astrogliosis around the injury impedes regeneration of axons through the injury, while activated microglia release inflammatory mediators. The persistent inflammatory response can lead to local progressive cell death. Modulating the astrocyte and microglial response to traumatic injury therefore has potential therapeutic benefit in brain repair. We examine the modulatory effect of a single bolus of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) in combination on astrocytes and microglia to acute cerebral injury. A combination of VEGF and PDGF (20 pg) was injected into the striatum of adult male Sprague-Dawley rats. The effects of treatment were assessed by quantitative immunofluorescence microscopy analyzing astrocytes and microglia across the stab injury over time. Treatment delayed the onset of astrogliosis in the centre and edge of the stab injury up to day 5; however, increased astrogliosis at areas remote to the stab injury up to day 5 was observed. A persistent astrocytic response was observed in the centre and edge of the stab injury up to day 60. Treatment altered microglia cell morphology and numbers across the stab injury, with a decrease in ramified microglia, but an increase in activated and phagocytic microglia up to day 5 after stab injury. The increased microglial response from 10 until day 60 was comprised of the ramified morphology. Thus, VEGF and PDGF applied at the same time as a stab injury to the brain initially delayed the inflammatory response up to day 5 but evoked a persistent astrogliosis and microglial response up to 60 days.

    Title Click--topology-independent Comparison of Biomolecular 3d Structures.
    Date November 2011
    Journal Nucleic Acids Research
    Excerpt

    Our server, CLICK: http://mspc.bii.a-star.edu.sg/click, is capable of superimposing the 3D structures of any pair of biomolecules (proteins, DNA, RNA, etc.). The server makes use of the Cartesian coordinates of the molecules with the option of using other structural features such as secondary structure, solvent accessible surface area and residue depth to guide the alignment. CLICK first looks for cliques of points (3-7 residues) that are structurally similar in the pair of structures to be aligned. Using these local similarities, a one-to-one equivalence is charted between the residues of the two structures. A least square fit then superimposes the two structures. Our method is especially powerful in establishing protein relationships by detecting similarities in structural subdomains, domains and topological variants. CLICK has been extensively benchmarked and compared with other popular methods for protein and RNA structural alignments. In most cases, CLICK alignments were statistically significantly better in terms of structure overlap. The method also recognizes conformational changes that may have occurred in structural domains or subdomains in one structure with respect to the other. For this purpose, the server produces complementary alignments to maximize the extent of detectable similarity. Various examples showcase the utility of our web server.

    Title Biological Insights from Topology Independent Comparison of Protein 3d Structures.
    Date October 2011
    Journal Nucleic Acids Research
    Excerpt

    Comparing and classifying the three-dimensional (3D) structures of proteins is of crucial importance to molecular biology, from helping to determine the function of a protein to determining its evolutionary relationships. Traditionally, 3D structures are classified into groups of families that closely resemble the grouping according to their primary sequence. However, significant structural similarities exist at multiple levels between proteins that belong to these different structural families. In this study, we propose a new algorithm, CLICK, to capture such similarities. The method optimally superimposes a pair of protein structures independent of topology. Amino acid residues are represented by the Cartesian coordinates of a representative point (usually the C(α) atom), side chain solvent accessibility, and secondary structure. Structural comparison is effected by matching cliques of points. CLICK was extensively benchmarked for alignment accuracy on four different sets: (i) 9537 pair-wise alignments between two structures with the same topology; (ii) 64 alignments from set (i) that were considered to constitute difficult alignment cases; (iii) 199 pair-wise alignments between proteins with similar structure but different topology; and (iv) 1275 pair-wise alignments of RNA structures. The accuracy of CLICK alignments was measured by the average structure overlap score and compared with other alignment methods, including HOMSTRAD, MUSTANG, Geometric Hashing, SALIGN, DALI, GANGSTA(+), FATCAT, ARTS and SARA. On average, CLICK produces pair-wise alignments that are either comparable or statistically significantly more accurate than all of these other methods. We have used CLICK to uncover relationships between (previously) unrelated proteins. These new biological insights include: (i) detecting hinge regions in proteins where domain or sub-domains show flexibility; (ii) discovering similar small molecule binding sites from proteins of different folds and (iii) discovering topological variants of known structural/sequence motifs. Our method can generally be applied to compare any pair of molecular structures represented in Cartesian coordinates as exemplified by the RNA structure superimposition benchmark.

    Title Toward Better Understanding of Protein Secondary Structure: Extracting Prediction Rules.
    Date August 2011
    Journal Ieee/acm Transactions on Computational Biology and Bioinformatics / Ieee, Acm
    Excerpt

    Although numerous computational techniques have been applied to predict protein secondary structure (PSS), only limited studies have dealt with discovery of logic rules underlying the prediction itself. Such rules offer interesting links between the prediction model and the underlying biology. In addition, they enhance interpretability of PSS prediction by providing a degree of transparency to the predicting model usually regarded as a black box. In this paper, we explore the generation and use of C4.5 decision trees to extract relevant rules from PSS predictions modeled with two-stage support vector machines (TS-SVM). The proposed rules were derived on the RS126 data set of 126 nonhomologous globular proteins and on the PSIPRED data set of 1,923 protein sequences. Our approach has produced sets of comprehensible, and often interpretable, rules underlying the PSS predictions. Moreover, many of the rules seem to be strongly supported by biological evidence. Further, our approach resulted in good prediction accuracy, few and usually compact rules, and rules that are generally of higher confidence levels than those generated by other rule extraction techniques.

    Title Multiple Perspectives on the Accessibility of E-learning in Canadian Colleges and Universities.
    Date March 2011
    Journal Assistive Technology : the Official Journal of Resna
    Excerpt

    An exploratory study identified and compared the views of 77 campus disability service providers, 38 professors, and 45 e-learning professionals from Canadian colleges and universities regarding their experiences with e-learning and its accessibility to students with disabilities. Findings indicate that all groups saw benefit in having someone who makes e-learning accessible to students with disabilities on campus and that problems related to e-learning accessibility were most likely to go to campus disability service providers and least likely to e-learning professionals. Only half of the participants indicated that professors are taught about e-learning accessibility, that there is someone on campus who makes e-learning accessible, that accessibility is a criterion for selecting new types of e-learning, and that their school has e-learning accessibility guidelines or policies. These findings suggest that important e-learning accessibility problems remain. Recommendations for colleges and universities on how to increase e-learning accessibility are provided.

    Title Progressive Loss of Dopaminergic Neurons Induced by Unilateral Rotenone Infusion into the Medial Forebrain Bundle.
    Date February 2011
    Journal Brain Research
    Excerpt

    Rotenone, a mitochondrial complex 1 inhibitor, causes oxidative damage via production of reactive oxygen species. We examined the pathophysiology of neuronal and glial cells of the nigrostriatal pathway following unilateral infusion of varying doses of rotenone into the substantia nigra or medial forebrain bundle of adult male Sprague-Dawley rats, sacrificed 14 and 60 days after infusion. Immunofluorescence techniques were used to qualitatively and quantitatively assay dopaminergic neurons, their projections, glial cells, synapses, and oxidative stress. Rotenone infusion into the substantia nigra at all concentrations caused extensive damage and tissue necrosis, therefore of limited relevance for producing a Parkinson disease model. Infusion of 0.5μg of rotenone targeting the medial forebrain bundle induced oxidative stress in dopaminergic neurons causing ongoing cell stress as defined by an elevation of stress granule and oxidative stress markers. This treatment resulted in the loss of tyrosine hydroxylase immunoreactive cells in the substantia nigra (p≤0.01) and loss of tyrosine hydroxylase immunoreactive nerve fibres and synaptic specialisations in the striatum (p≤0.01). The infusion of 0.5μg of rotenone also caused an increase in astrocytes and microglial cells in the substantia nigra in comparison to control (p≤0.01). We examined the time-dependent reduction of tyrosine hydroxylase-positive nerve fibres and cell bodies in the striatum and substantia nigra respectively, with a progressive reduction evident 60days after infusion (p≤0.01, p≤0.05). Dopaminergic axons exposed to low-dose rotenone undergo oxidative stress, with a resultant ongoing loss of dopaminergic neurons, providing an animal model relevant to Parkinson disease.

    Title Products of Vitamin D3 or 7-dehydrocholesterol Metabolism by Cytochrome P450scc Show Anti-leukemia Effects, Having Low or Absent Calcemic Activity.
    Date January 2011
    Journal Plos One
    Excerpt

    Cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,23(OH)(2)D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3 (1,20(OH)(2)D3). It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed to 20(OH)7DHP. UVB induces transformation of the steroidal 5,7-dienes to pregnacalciferol (pD) and a lumisterol-like compounds (pL).

    Title Purified Mouse Cyp27b1 Can Hydroxylate 20,23-dihydroxyvitamin D3, Producing 1alpha,20,23-trihydroxyvitamin D3, Which Has Altered Biological Activity.
    Date January 2011
    Journal Drug Metabolism and Disposition: the Biological Fate of Chemicals
    Excerpt

    20,23-Dihydroxyvitamin D(3) [20,23(OH)(2)D(3)] is a biologically active metabolite produced by the action of cytochrome P450scc (CYP11A1) on vitamin D(3). It inhibits keratinocyte proliferation, stimulates differentiation, and inhibits nuclear factor-kappaB activity, working as a vitamin D receptor agonist. We have tested the ability of purified mouse 25-hydroxyvitamin D(3) 1alpha-hydroxylase (CYP27B1) to add a 1alpha-hydroxyl group to this vitamin D analog and determined whether this altered its biological activity. 20,23(OH)(2)D(3) incorporated into phospholipid vesicles was converted to a single product by CYP27B1, confirmed to be 1alpha,20,23-trihydroxyvitamin D(3) [1,20,23(OH)(3)D(3)] by mass spectrometry and NMR. The 20,23(OH)(2)D(3) was a relatively poor substrate for CYP27B1 compared with the normal substrate, 25-hydroxyvitamin D(3), displaying a 5-fold higher K(m) and 8-fold lower k(cat) value. Both 20,23(OH)(2)D(3) and 1,20,23(OH)(3)D(3) decreased neonatal human epidermal keratinocyte proliferation, showing significant effects at a lower concentration (0.1 nM) than that seen for 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] at 24 h of treatment. Both compounds also decreased cell biomass relative to that of control cells, measured by staining with sulforhodamine B. They caused little stimulation of the expression of the vitamin D receptor at the mRNA level compared with the 30-fold induction observed with the same concentration (100 nM) of 1,25(OH)(2)D(3) at 24 h. Addition of a 1alpha-hydroxyl group to 20,23(OH)(2)D(3) greatly enhanced its ability to stimulate the expression of the CYP24 gene but not to the extent seen with 1,25(OH)(2)D(3). This study shows that purified CYP27B1 can add a 1alpha-hydroxyl group to 20,23(OH)(2)D(3) with the product showing altered biological activity, especially for the stimulation of CYP24 gene expression.

    Title Fuzzy Cmac With Incremental Bayesian Ying-yang Learning and Dynamic Rule Construction.
    Date October 2010
    Journal Ieee Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the Ieee Systems, Man, and Cybernetics Society
    Excerpt

    Inspired by the philosophy of ancient Chinese Taoism, Xu's Bayesian ying-yang (BYY) learning technique performs clustering by harmonizing the training data (yang) with the solution (ying). In our previous work, the BYY learning technique was applied to a fuzzy cerebellar model articulation controller (FCMAC) to find the optimal fuzzy sets; however, this is not suitable for time series data analysis. To address this problem, we propose an incremental BYY learning technique in this paper, with the idea of sliding window and rule structure dynamic algorithms. Three contributions are made as a result of this research. First, an online expectation-maximization algorithm incorporated with the sliding window is proposed for the fuzzification phase. Second, the memory requirement is greatly reduced since the entire data set no longer needs to be obtained during the prediction process. Third, the rule structure dynamic algorithm with dynamically initializing, recruiting, and pruning rules relieves the "curse of dimensionality" problem that is inherent in the FCMAC. Because of these features, the experimental results of the benchmark data sets of currency exchange rates and Mackey-Glass show that the proposed model is more suitable for real-time streaming data analysis.

    Title Metabolism of Substrates Incorporated into Phospholipid Vesicles by Mouse 25-hydroxyvitamin D3 1alpha-hydroxylase (cyp27b1).
    Date April 2010
    Journal The Journal of Steroid Biochemistry and Molecular Biology
    Excerpt

    CYP27B1 catalyzes the 1alpha-hydroxylation of 25-hydroxyvitamin D3 to 1alpha,25-dihydroxyvitamin D3, the hormonally active form of vitamin D3. To further characterize mouse CYP27B1, it was expressed in Escherichia coli, purified and its activity measured on substrates incorporated into phospholipid vesicles, which served as a model of the inner mitochondrial membrane. 25-Hydroxyvitamin D3 and 25-hydroxyvitamin D2 in vesicles underwent 1alpha-hydroxylation with similar kinetics, the catalytic rate constants (k(cat)) were 41 and 48mol/min/mol P450, respectively, while K(m) values were 5.9 and 4.6mmol/mol phospholipid, respectively. CYP27B1 showed inhibition when substrate concentrations in the membrane were greater than 4 times K(m), more pronounced with 25-hydroxyvitamin D3 than 25-hydroxyvitamin D2. Higher catalytic efficiency was seen in vesicles prepared from dioleoyl phosphatidylcholine and cardiolipin than for dimyristoyl phosphatidylcholine vesicles. CYP27B1 also catalyzed 1alpha-hydroxylation of vesicle-associated 24R,25-dihydroxyvitamin D3 and 20-hydroxyvitamin D3, and 25-hydroxylation of 1alpha-hydroxyvitamin D3 and 1alpha-hydroxyvitamin D2, but with much lower efficiency than for 25(OH)D3. This study shows that CYP27B1 can hydroxylate 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 associated with phospholipid membranes with the highest activity yet reported for the enzyme. The expressed enzyme has low activity at higher concentrations of 25-hydroxyvitamin D in membranes, revealing that substrate inhibition may contribute to the regulation of the activity of this enzyme.

    Title Effects of Atorvastatin and N-3 Fatty Acid Supplementation on Vldl Apolipoprotein C-iii Kinetics in Men with Abdominal Obesity.
    Date April 2010
    Journal The American Journal of Clinical Nutrition
    Excerpt

    Disturbed apolipoprotein (apo) C-III metabolism in obese subjects may account for hypertriglyceridemia and increased risk of cardiovascular disease. Atorvastatin and fish oils decrease plasma triglycerides and VLDL concentrations, but the underlying mechanisms are not fully understood.

    Title 20,23-dihydroxyvitamin D3, Novel P450scc Product, Stimulates Differentiation and Inhibits Proliferation and Nf-kappab Activity in Human Keratinocytes.
    Date March 2010
    Journal Journal of Cellular Physiology
    Excerpt

    We have examined effects of the 20,23-dihydroxyvitamin D3 (20,23(OH)2D3), on differentiation and proliferation of human keratinocytes and the anti-inflammatory potential of 20,23(OH)2D3 from its action on nuclear factor-kappaB (NF-kappaB). 20,23(OH)2D3 inhibited growth of keratinocytes with a potency comparable to that for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Cell cycle analysis showed that this inhibition was associated with G1/G0 and G2/M arrests. 20,23(OH)2D3 stimulated production of involucrin mRNA and inhibited production of cytokeratin 14 mRNA in a manner similar to that seen for 1,25(OH)2D3. Flow cytometry showed that these effects were accompanied by increased involucrin protein expression, and an increase in the cell size and granularity. Silencing of the vitamin D receptor (VDR) by corresponding siRNA abolished the stimulatory effect on involucrin gene expression demonstrating an involvement of VDR in 20,23(OH)2D3 action. This mode of action was further substantiated by stimulation of CYP24 gene expression and stimulation of the CYP24 promoter-driven reporter gene activity. 20,23(OH)2D3 displayed several fold lower potency for induction of CYP24 gene expression than 1,25(OH)2D3. Finally, 20,23(OH)2D3 inhibited the transcriptional activity of NF-kappaB in keratinocytes as demonstrated by EMSA, NF-kappaB-driven reporter gene activity assays and measurements of translocation of p65 from the cytoplasm to the nucleus. These inhibitory effects were connected with stimulation of the expression of IkappaBalpha with subsequent sequestration of NF-kappaB in the cytoplasm and consequent attenuation of transcriptional activity. In summary, we have characterized 20,23(OH)2D3 as a novel secosteroidal regulator of keratinocytes proliferation and differentiation and a modifier of their immune activity.

    Title 20-hydroxycholecalciferol, Product of Vitamin D3 Hydroxylation by P450scc, Decreases Nf-kappab Activity by Increasing Ikappab Alpha Levels in Human Keratinocytes.
    Date November 2009
    Journal Plos One
    Excerpt

    The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1) to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB) plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol) as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR), 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

    Title Di-codon Usage for Classification of Genes.
    Date November 2009
    Journal Bio Systems
    Excerpt

    Genes are often classified into biologically related groups so that inferences on their functions can be made. This paper demonstrates that the di-codon usage is a useful feature for gene classification and gives better classification accuracy than the codon usage. Our experiments with different classifiers show that support vector machines performs better than other classifiers in classifying genes by using di-codon usage as features. The method is illustrated on 1841 HLA sequences which are classified into two major classes, HLA-I and HLA-II, and further classified into the subclasses of major classes. By using both codon and di-codon features, we show near perfect accuracies in the classification of HLA molecules into major classes and their sub-classes.

    Title Protein-functionalized Hairy Diamond Nanoparticles.
    Date November 2009
    Journal Langmuir : the Acs Journal of Surfaces and Colloids
    Excerpt

    Diazonium salt chemistry and atom transfer radical polymerization (ATRP) were combined in view of preparing new bioactive hairy diamond nanoparticles containing, or potentially containing, nitrogen-vacancy (NV) fluorescent centers (fluorescent nanodiamonds, or fNDs). fNDs were modified by ATRP initiators using the electroless reduction of the diazonium salt BF(4)(-),(+)N(2)-C(6)H(4)-CH(CH(3))-Br. The strongly bound aryl groups -C(6)H(4)-CH(CH(3))-Br efficiently initiated the ATRP of tert-butyl methacrylate (tBMA) at the surface of the nanodiamonds, which resulted in obtaining ND-PtBMA hybrids. The grafted chain thickness, estimated from X-ray photoelectron spectroscopy (XPS), was found to increase linearly with respect to time before reaching a plateau value of ca. 2 nm. These nanoobjects were further hydrolyzed into ND-PMAA (where PMAA is the poly(methacrylic acid) graft) and further decorated by bovine serum albumin through the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling procedure.

    Title Quebec Breast Cancer Screening Program: a Study of the Perceptions of Physicians in Laval, Que.
    Date August 2009
    Journal Canadian Family Physician Médecin De Famille Canadien
    Excerpt

    To identify physicians' perceptions of breast cancer prevention in order to generate strategies to increase women's participation in the Quebec breast cancer screening program (QBCSP).

    Title Gene Classification Using Codon Usage and Support Vector Machines.
    Date August 2009
    Journal Ieee/acm Transactions on Computational Biology and Bioinformatics / Ieee, Acm
    Excerpt

    A novel approach for gene classification, which adopts codon usage bias as input feature vector for classification by support vector machines (SVM) is proposed. The DNA sequence is first converted to a 59-dimensional feature vector where each element corresponds to the relative synonymous usage frequency of a codon. As the input to the classifier is independent of sequence length and variance, our approach is useful when the sequences to be classified are of different lengths, a condition that homology-based methods tend to fail. The method is demonstrated by using 1,841 Human Leukocyte Antigen (HLA) sequences which are classified into two major classes: HLA-I and HLA-II; each major class is further subdivided into sub-groups of HLA-I and HLA-II molecules. Using codon usage frequencies, binary SVM achieved accuracy rate of 99.3% for HLA major class classification and multi-class SVM achieved accuracy rates of 99.73% and 98.38% for sub-class classification of HLA-I and HLA-II molecules, respectively. The results show that gene classification based on codon usage bias is consistent with the molecular structures and biological functions of HLA molecules.

    Title Metabolism of Vitamin D2 to 17,20,24-trihydroxyvitamin D2 by Cytochrome P450scc (cyp11a1).
    Date July 2009
    Journal Drug Metabolism and Disposition: the Biological Fate of Chemicals
    Excerpt

    As well as catalyzing the conversion of cholesterol to pregnenolone for steroid synthesis, cytochrome P450scc (P450scc) can also metabolize vitamins D2 (D2) and D3 (D3). Two products of D2 metabolism by P450scc, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2, have been identified and shown to exert biological activity on cultured keratinocytes. The aim of this study was to fully characterize the metabolism of D2 by P450scc, including identifying additional products and determining the kinetics of D2 metabolism. Two new products were isolated by reverse-phase high-performance liquid chromatography: a dihydroxy metabolite with a hydroxyl group at C20 plus another unidentified position, and a trihydroxy metabolite identified by NMR as 17,20,24-trihydroxyvitamin D2. Kinetics of D2 metabolism was determined with substrate solubilized by 2-hydroxypropyl-beta-cyclodextrin or incorporated into phospholipid vesicles. In 2-hydroxypropyl-beta-cyclodextrin, D2 was hydroxylated at C20 with a k(cat)/K(m) 5-fold lower than that for cholesterol metabolism. 20-Hydroxyvitamin D2 was hydroxylated with a similar k(cat)/K(m) to D2, whereas 17,20-dihydroxyvitamin D2 was hydroxylated with a lower k(cat)/K(m) than that for D2 in 2-hydroxypropyl-beta-cyclodextrin. In vesicles, D2 displayed a high K(m) relative to that for cholesterol, but hydroxylation resulted in products that could be further hydroxylated with relatively low K(m) values. We conclude that P450scc catalyzes three sequential hydroxylations of D2 producing 20-hydroxyvitamin D2, 17,20-dihydroxyvitamin D2, and 17,20,24-trihydroxyvitamin D2, which dissociate from the active site of P450scc and accumulate in the reaction mixture. D2 metabolism occurs with lower efficiency (k(cat)/K(m)) than that observed for both cholesterol and D3 metabolism by P450scc.

    Title Metabolism of 1alpha-hydroxyvitamin D3 by Cytochrome P450scc to Biologically Active 1alpha,20-dihydroxyvitamin D3.
    Date March 2009
    Journal The Journal of Steroid Biochemistry and Molecular Biology
    Excerpt

    Cytochrome P450scc (CYP11A1) metabolizes vitamin D3 to 20-hydroxyvitamin D3 as the major product, with subsequent production of dihydroxy and trihydroxy derivatives. The aim of this study was to determine whether cytochrome P450scc could metabolize 1alpha-hydroxyvitamin D3 and whether products were biologically active. The major product of 1alpha-hydroxyvitamin D3 metabolism by P450scc was identified by mass spectrometry and NMR as 1alpha,20-dihydroxyvitamin D3. Mass spectrometry of minor metabolites revealed the production of another dihydroxyvitamin D3 derivative, two trihydroxy-metabolites made via 1alpha,20-dihydroxyvitamin D3 and a tetrahydroxyvitamin D3 derivative. The Km for 1alpha-hydroxyvitamin D3 determined for P450scc incorporated into phospholipid vesicles was 1.4 mol substrate/mol phospholipid, half that observed for vitamin D3. The kcat was 3.0 mol/min/mol P450scc, 6-fold lower than that for vitamin D3. 1alpha,20-Dihydroxyvitamin D3 inhibited DNA synthesis by human epidermal HaCaT keratinocytes propagated in culture, in a time- and dose-dependent fashion, with a potency similar to that of 1alpha,25-dihydroxyvitamin D3. 1alpha,20-Dihydroxyvitamin D3 (10 microM) enhanced CYP24 mRNA levels in HaCaT keratinocytes but the potency was much lower than that reported for 1alpha,25-dihydroxyvitamin D3. We conclude that the presence of the 1-hydroxyl group in vitamin D3 does not alter the major site of hydroxylation by P450scc which, as for vitamin D3, is at C20. The major product, 1alpha,20-dihydroxyvitamin D3, displays biological activity on keratinocytes and therefore might be useful pharmacologically.

    Title Rational Design and Synthesis of 4-((1r,2r)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (pf-998425), a Novel, Nonsteroidal Androgen Receptor Antagonist Devoid of Phototoxicity for Dermatological Indications.
    Date November 2008
    Journal Journal of Medicinal Chemistry
    Excerpt

    4-((1 R,2 R)-2-Hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile [PF-0998425, (-)- 6a] is a novel, nonsteroidal androgen receptor antagonist for sebum control and treatment of androgenetic alopecia. It is potent, selective, and active in vivo. The compound is rapidly metabolized systemically, thereby reducing the risk of unwanted systemic side effects due to its primary pharmacology. (-)- 6a was tested negative in the 3T3 NRU assay, validating our rationale that reduction of conjugation might reduce potential phototoxicity.

    Title Muscarinic Receptor Knockout Mice Confirm Involvement of M3 Receptor in Endothelium-dependent Vasodilatation in Mouse Arteries.
    Date November 2008
    Journal Journal of Cardiovascular Pharmacology
    Excerpt

    The aim of the study was to determine which cholinergic muscarinic receptor subtype is responsible for the endothelium-dependent vasodilatation evoked by acetylcholine (ACh) in mouse arteries. Endothelium-dependent relaxations were evaluated using isometric tension measurement of ring from femoral and aortic artery of M1, M2, and M3 knockout (KO) mice. Rings of femoral and aortic artery from M3 KO mice did not exhibit relaxation at the opposite of rings from M1+M2 KO and wild-type (WT) mice, which were relaxed by ACh. The proportion of endothelial cells responsive to ACh, as manifested by an increase in cytosolic free calcium ([Ca]i), was also observed on the intima of aorta wall in vitro by using laser line confocal microscopy. Of the cells from M3 KO mice and M1+M2 KO mice, 4% and 23%, respectively, responded to ACh in comparison with 20 % in WT mice. These results show that in the endothelium from femoral and aortic artery, the larger proportion of cells that express M3 receptor is responsible for the specificity of the M3 receptor subtype for endothelium-dependent relaxation caused by ACh.

    Title Kinetics of Vitamin D3 Metabolism by Cytochrome P450scc (cyp11a1) in Phospholipid Vesicles and Cyclodextrin.
    Date October 2008
    Journal The International Journal of Biochemistry & Cell Biology
    Excerpt

    Vitamin D3 can be hydroxylated sequentially by cytochrome P450scc (CYP11A1) producing 20-hydroxyvitamin D3, 20,23-dihydroxyvitamin D3 and 17,20,23-trihydroxyvitamin D3. The aim of this study was to characterize the ability of vitamin D3 to associate with phospholipid vesicles and to determine the kinetics of metabolism of vitamin D3 by P450scc in vesicles and in 2-hydroxypropyl-beta-cyclodextrin (cyclodextrin). Gel filtration of phospholipid vesicles showed that the vitamin D3 remained quantitatively associated with the phospholipid membrane. Vitamin D3 exchanged between vesicles at a rate 3.8-fold higher than for cholesterol exchange and was stimulated by N-62 StAR protein. The Km of P450scc for vitamin D3 in vesicles was 3.3 mol vitamin D3/mol phospholipid and the rate of conversion of vitamin D3 to 20-hydroxyvitamin D3 was first order with respect to the vitamin D3 concentration for the range of concentrations of vitamin D3 that could be incorporated into the vesicle membrane. 20-Hydroxyvitamin D3 was further hydroxylated by P450scc in vesicles, producing primarily 20,23-dihydroxyvitamin D3, with Km and kcat values 22- and 6-fold lower than those for vitamin D3, respectively. 20,23-dihydroxyvitamin D3 was converted to 17,20,23-trihydroxyvitamin D3 with even lower Km and kcat values. Vitamin D3 and cholesterol were metabolized with comparable efficiencies in cyclodextrin, but the Km for both showed a strong dependence on the cyclodextrin concentration, decreasing with decreasing cyclodextrin. This study shows that vitamin D3 quantitatively associates with phospholipid vesicles, can exchange between membranes, and can be hydroxylated by membrane-associated P450scc but with lower efficiency than for cholesterol hydroxylation. The kcat values for metabolism of vitamin D3 in vesicles and 0.45% cyclodextrin are similar, but the ability to solubilize vitamin D3 at a concentration higher than its Km makes the cyclodextrin system more efficient for producing the hydroxyvitamin D3 metabolites for further characterization.

    Title 20-hydroxyvitamin D3, a Product of Vitamin D3 Hydroxylation by Cytochrome P450scc, Stimulates Keratinocyte Differentiation.
    Date September 2008
    Journal The Journal of Investigative Dermatology
    Excerpt

    It has been shown that mammalian cytochrome P450scc can metabolize vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,22(OH)2D3. To define the biological significance of this pathway, we tested the effects of 20(OH)D3 on the differentiation program of keratinocytes and on the expression of enzymes engaged in vitamin D3 metabolism. Immortalized HaCaT and adult human epidermal keratinocytes were used as a model and the effects of 20(OH)D3 were compared with those of 25(OH)D3 and 1,25(OH)2D3. 20(OH)D3 inhibited proliferation and caused G2/M arrest. 20(OH)D3 stimulated involucrin and inhibited cytokeratin 14 expression. The potency of 20(OH)D3 was comparable to that of 1,25(OH)2D3. 20(OH)D3 decreased the expression of cytochrome P450 enzyme (CYP)27A1 and CYP27B1, however, having only slight effect on CYP24. The effect of 20(OH)D3 was dependent on the vitamin D receptor (VDR). As shown by electrophoretic mobility shift assay, 20(OH)D3 stimulated the binding of nuclear proteins to the VDRE. Transfection of cells with VDR-specific siRNA decreased 20(OH)D3-stimulated transcriptional activity of the VDRE promoter and the expression of involucrin and CYP24 mRNA. Therefore, the above studies identify 20(OH)D3 as a biologically active secosteroid that induces keratinocyte differentiation. These data imply that the previously unreported pathway of vitamin D3 metabolism by P450scc may have wider biological implications depending, for example, on the extent of adrenal gland or cutaneous metabolism.

    Title Pathways and Products for the Metabolism of Vitamin D3 by Cytochrome P450scc.
    Date July 2008
    Journal The Febs Journal
    Excerpt

    Cytochrome P450scc (CYP11A1) can hydroxylate vitamin D3 to produce 20-hydroxyvitamin D3 and other poorly characterized hydroxylated products. The present study aimed to identify all the products of vitamin D3 metabolism by P450scc, as well as the pathways leading to their formation. Besides 20-hydroxyvitamin D3, other major metabolites of vitamin D3 were a dihydroxyvitamin D3 and a trihydroxyvitamin D3 product. The dihydroxyvitamin D3 was clearly identified as 20,23-dihydroxyvitamin D3 by NMR, in contrast to previous reports that postulated hydroxyl groups in positions 20 and 22. NMR of the trihydroxy product identified it as 17alpha,20,23-trihydroxyvitamin D3. This product could be directly produced by P450scc acting on 20,23-dihydroxyvitamin D3, confirming that hydroxyl groups are present at positions 20 and 23. Three minor products of D3 metabolism by P450scc were identified by MS and by examining their subsequent metabolism by P450scc. These products were 23-hydroxyvitamin D3, 17alpha-hydroxyvitamin D3 and 17alpha,20-dihydroxyvitamin D3 and arise from the three P450scc-catalysed hydroxylations occurring in a different order. We conclude that the major pathway of vitamin D3 metabolism by P450scc is: vitamin D3 --> 20-hydroxyvitamin D3 --> 20,23-dihydroxyvitamin D3 --> 17alpha,20,23-trihydroxyvitamin D3. The major products dissociate from the P450scc active site and accumulate at a concentration well above the P450scc concentration. Our new identification of the major dihydroxyvitamin D3 product as 20,23-dihydroxyvitamin D3, rather than 20,22-dihydroxyvitamin D3, explains why there is no cleavage of the vitamin D3 side chain, unlike the metabolism of cholesterol by P450scc.

    Title Why and According to What Consultation Profiles Do Female Sex Workers Consult Health Care Professionals? A Study Conducted in Laval, Québec.
    Date June 2008
    Journal Health Care for Women International
    Excerpt

    We carried out a study to understand help-seeking behavior among female sex workers in order to bring adequate health care and services to this population at risk for sexually transmitted infection (STI) and human immunodeficiency virus (HIV) transmissions. Data were collected by means of questionnaires, focus groups, and in-depth individual interviews. Analysis reveals that the respondents are familiar with and have access to the health care system. Over 80% claimed to have consulted a health professional during the preceding 12 months. Gynecological, psychosocial, respiratory, digestive, and drug addiction problems were the most frequent. Only a third of the respondents received care and services related to STIs. Data are displayed as three consultation profiles, one of which only tends to foster continuity and comprehensive health care, including screening and treatment of STIs.

    Title Prediction of Protein Secondary Structure with Two-stage Multi-class Svms.
    Date May 2008
    Journal International Journal of Data Mining and Bioinformatics
    Excerpt

    Bioinformatics techniques to Protein Secondary Structure (PSS) prediction mostly depend on the information available in amino acid sequences. In this paper, we propose a two-stage Multi-class Support Vector Machine (MSVM) approach, where the second MSVM predictor is introduced at the output of the first stage MSVM to capture the contextual relationship among secondary structure elements in order to minimise the generalisation error in the prediction. By using position-specific scoring matrices generated by PSI-BLAST, the two-stage MSVM approach achieves Q3 accuracies of 78.0% and 76.3% on the RS126 dataset of 126 non-homologous globular proteins and the CB396 dataset of 396 non-homologous proteins, respectively, which are better than the scores reported on both datasets to date. By using MSVM, the present prediction scheme significantly achieves 2-6% and 3-15% of improvement in Q3 and Sov accuracies, respectively, on the two datasets. On larger blind-test datasets from PSIPRED, CASP4 and EVA datasets, two-stage MSVM approach achieves Q3 accuracies from 77.0% to 79.5%.

    Title Plasma Apolipoprotein C-iii Transport in Centrally Obese Men: Associations with Very Low-density Lipoprotein Apolipoprotein B and High-density Lipoprotein Apolipoprotein A-i Metabolism.
    Date April 2008
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    Apolipoprotein (apo) C-III is associated with hypertriglyceridemia and progression of cardiovascular disease. Plasma apoC-III is elevated in centrally obese men, and we hypothesized that the kinetics of apoC-III are disturbed in these subjects.

    Title Fcmac-byy: Fuzzy Cmac Using Bayesian Ying-yang Learning.
    Date November 2006
    Journal Ieee Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the Ieee Systems, Man, and Cybernetics Society
    Excerpt

    As an associative memory neural network model, the cerebellar model articulation controller (CMAC) has attractive properties of fast learning and simple computation, but its rigid structure makes it difficult to approximate certain functions. This research attempts to construct a novel neural fuzzy CMAC, in which Bayesian Ying-Yang (BYY) learning is introduced to determine the optimal fuzzy sets, and a truth-value restriction inference scheme is subsequently employed to derive the truth values of the rule weights of implication rules. The BYY is motivated from the famous Chinese ancient Ying-Yang philosophy: everything in the universe can be viewed as a product of a constant conflict between opposites-Ying and Yang, a perfect status is reached when Ying and Yang achieve harmony. The proposed fuzzy CMAC (FCMAC)-BYY enjoys the following advantages. First, it has a higher generalization ability because the fuzzy rule sets are systematically optimized by BYY; second, it reduces the memory requirement of the network by a significant degree as compared to the original CMAC; and third, it provides an intuitive fuzzy logic reasoning and has clear semantic meanings. The experimental results on some benchmark datasets show that the proposed FCMAC-BYY outperforms the existing representative techniques in the research literature.

    Title Factorial Study of the Effect of N-3 Fatty Acid Supplementation and Atorvastatin on the Kinetics of Hdl Apolipoproteins A-i and A-ii in Men with Abdominal Obesity.
    Date August 2006
    Journal The American Journal of Clinical Nutrition
    Excerpt

    Disturbed HDL metabolism in insulin-resistant, obese subjects may account for an increased risk of cardiovascular disease. Fish oils and atorvastatin increase plasma HDL cholesterol, but the underlying mechanisms responsible for this change are not fully understood.

    Title Two-stage Support Vector Regression Approach for Predicting Accessible Surface Areas of Amino Acids.
    Date August 2006
    Journal Proteins
    Excerpt

    We address the problem of predicting solvent accessible surface area (ASA) of amino acid residues in protein sequences, without classifying them into buried and exposed types. A two-stage support vector regression (SVR) approach is proposed to predict real values of ASA from the position-specific scoring matrices generated from PSI-BLAST profiles. By adding SVR as the second stage to capture the influences on the ASA value of a residue by those of its neighbors, the two-stage SVR approach achieves improvements of mean absolute errors up to 3.3%, and correlation coefficients of 0.66, 0.68, and 0.67 on the Manesh dataset of 215 proteins, the Barton dataset of 502 nonhomologous proteins, and the Carugo dataset of 338 proteins, respectively, which are better than the scores published earlier on these datasets. A Web server for protein ASA prediction by using a two-stage SVR method has been developed and is available (http://birc.ntu.edu.sg/~ pas0186457/asa.html).

    Title Use of Intralipid for Kinetic Analysis of Hdl Apoc-iii: Evidence for a Homogeneous Kinetic Pool of Apoc-iii in Plasma.
    Date July 2006
    Journal Journal of Lipid Research
    Excerpt

    Apolipoprotein C-III (apoC-III) is an important regulator of lipoprotein metabolism. Radioisotope and stable isotope kinetic studies show differing results in relation to the kinetics of apoC-III in HDL. Kinetic analysis of HDL apoC-III may be difficult because of its low concentration, as well as the presence of other apoproteins at higher concentration, in the HDL fraction. We used Intralipid(R) (IL), known to preferentially extract apoC proteins from plasma, as a means of extracting apoC-III from HDL before apoprotein separation by isoelectric focusing gel electrophoresis for the measurement of tracer enrichment. Protein purity was assessed by an isoleucine-to-leucine (Ile/Leu) ratio, as apoC-III contains no isoleucine. We compared apoC-III kinetics in 14 men using a bolus infusion of deuterated leucine. The Ile/Leu ratio for IL-extracted HDL (IL-HDL) apoC-III (3.0 +/- 0.7%) was not different from that of VLDL apoC-III (2.6 +/- 0.6%) but was significantly lower than that of untreated HDL apoC-III (9.0 +/- 2.9%) (P < 0.001). The isotopic enrichment curves and fractional catabolic rates (FCRs) for IL-HDL apoC-III were not different from those of VLDL apoC-III. In contrast, HDL apoC-III had significantly lower isotopic enrichments and FCRs than IL-HDL apoC-III (P < 0.001). In conclusion, this simple IL method can be used to isolate apoC-III from HDL with minimal interference from other HDL apoproteins, and it demonstrates that the kinetics of apoC-III in VLDL and HDL are similar, supporting the concept of a single kinetically homogeneous pool of apoC-III in plasma.

    Title Apolipoproteins C-iii and A-v As Predictors of Very-low-density Lipoprotein Triglyceride and Apolipoprotein B-100 Kinetics.
    Date May 2006
    Journal Arteriosclerosis, Thrombosis, and Vascular Biology
    Excerpt

    We investigated the associations between plasma very-low-density lipoprotein (VLDL)-apolipoprotein (apo)C-III and apoA-V concentrations and the kinetics of VLDL-apoB-100 and VLDL triglycerides in 15 men. We also explored the relationship between these parameters of VLDL metabolism and VLDL-apoC-III kinetics.

    Title Convergent, Parallel Synthesis of a Series of Beta-substituted 1,2,4-oxadiazole Butanoic Acids As Potent and Selective Alpha(v)beta3 Receptor Antagonists.
    Date April 2006
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the integrin alpha(v)beta3 and, in addition, show selectivity relative to the other beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6.

    Title Prediction of Protein Relative Solvent Accessibility with a Two-stage Svm Approach.
    Date March 2006
    Journal Proteins
    Excerpt

    Information on relative solvent accessibility (RSA) of amino acid residues in proteins provides valuable clues to the prediction of protein structure and function. A two-stage approach with support vector machines (SVMs) is proposed, where an SVM predictor is introduced to the output of the single-stage SVM approach to take into account the contextual relationships among solvent accessibilities for the prediction. By using the position-specific scoring matrices (PSSMs) generated by PSI-BLAST, the two-stage SVM approach achieves accuracies up to 90.4% and 90.2% on the Manesh data set of 215 protein structures and the RS126 data set of 126 nonhomologous globular proteins, respectively, which are better than the highest published scores on both data sets to date. A Web server for protein RSA prediction using a two-stage SVM method has been developed and is available (http://birc.ntu.edu.sg/~pas0186457/rsa.html).

    Title Two-stage Multi-class Support Vector Machines to Protein Secondary Structure Prediction.
    Date April 2005
    Journal Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
    Excerpt

    Bioinformatics techniques to protein secondary structure (PSS) prediction are mostly single-stage approaches in the sense that they predict secondary structures of proteins by taking into account only the contextual information in amino acid sequences. In this paper, we propose two-stage Multi-class Support Vector Machine (MSVM) approach where a MSVM predictor is introduced to the output of the first stage MSVM to capture the sequential relationship among secondary structure elements for the prediction. By using position specific scoring matrices, generated by PSI-BLAST, the two-stage MSVM approach achieves Q3 accuracies of 78.0% and 76.3% on the RS126 dataset of 126 nonhomologous globular proteins and the CB396 dataset of 396 nonhomologous proteins, respectively, which are better than the highest scores published on both datasets to date.

    Title Multi-class Support Vector Machines for Protein Secondary Structure Prediction.
    Date March 2005
    Journal Genome Informatics. International Conference on Genome Informatics
    Excerpt

    The solution of binary classification problems using the Support Vector Machine (SVM) method has been well developed. Though multi-class classification is typically solved by combining several binary classifiers, recently, several multi-class methods that consider all classes at once have been proposed. However, these methods require resolving a much larger optimization problem and are applicable to small datasets. Three methods based on binary classifications: one-against-all (OAA), one-against-one (OAO), and directed acyclic graph (DAG), and two approaches for multi-class problem by solving one single optimization problem, are implemented to predict protein secondary structure. Our experiments indicate that multi-class SVM methods are more suitable for protein secondary structure (PSS) prediction than the other methods, including binary SVMs, because their capacity to solve an optimization problem in one step. Furthermore, in this paper, we argue that it is feasible to extend the prediction accuracy by adding a second-stage multi-class SVM to capture the contextual information among secondary structural elements and thereby further improving the accuracies. We demonstrate that two-stage SVMs perform better than single-stage SVM techniques for PSS prediction using two datasets and report a maximum accuracy of 79.5%.

    Title Validation of an Hplc Method on Short Columns to Assay Ketoconazole and Formaldehyde in Shampoo.
    Date January 2004
    Journal Journal of Pharmaceutical and Biomedical Analysis
    Excerpt

    An HPLC method to determine simultaneously ketoconazole and formaldehyde in an anti-dandruff shampoo, originally developed on a long column, was transferred to two short columns with similar stationary phase properties, but with a length of at the most 30% of the initial one. Using the conventional column as reference, the fast HPLC methods on the short columns were validated. The validation characteristics consisted of selectivity, linearity range, precision (repeatability and time-different intermediate precision), bias and robustness. For the ketoconazole assay, linearity for peak area was found in the concentration range up to 0.20 mg/ml. For formaldehyde, two calibration ranges (0-10 x 10(-5) and 0-10 x 10(-4)%) were linear, both for peak area and height. The assays for both ketoconazole and formaldehyde in these ranges showed no bias and an acceptable precision, although the precision found with the short columns was slightly worse than with the long one. The robustness tests were performed applying a Plackett-Burman design. For the ketoconazole assay, 6 factors were examined in a 12 experiments design and for formaldehyde, 11 factors in 16 experiments. The methods were found to be robust. Despite the somewhat less good precision the transfer seems to be successful and the obtained assays on the short columns are applicable for fast routine analysis.

    Title Evaluating the Fabreville Heart Health Program in Laval, Canada: a Dialogue Between Two Paradigms, Positivism and Constructivism.
    Date September 2003
    Journal Health Promotion International
    Excerpt

    As part of the Canadian Federal-Provincial Initiative in Heart Health, the goal of the Fabreville Heart Health Program was to sensitize a district of Laval, Quebec's second most populous city, to heart-healthy behaviours. The program was planned and implemented by a committee composed of Fabreville community leaders and professionals from the Public Health Department. Between 1992 and 1994, intervention objectives were defined by the department in terms of changing individual behaviours associated with cardiovascular risk factors, namely diet, sedentariness and smoking, as well as adapting physical and social environments to facilitate these changes. However, from 1994 to its conclusion in 1997, the program was re-oriented to engage the population in mobilizing their own community and taking charge of interventions themselves. Actions then became dependent on the interests and motivation of Fabreville residents to transform their lifestyles and aspects of their physical environment. The initial evaluation process, based on the positivist paradigm, was designed to measure changes in individual behaviours and certain physical environments, such as an increase in designated non-smoking areas. However, following the re-orientation towards community mobilization, it was decided that evaluation should go beyond the professional production of data to include a process of the collective construction of knowledge. Evaluation methodology then became based on the constructivist paradigm. Yet field constraints such as lack of community involvement in both leadership and process evaluation, and the need to ensure evaluation standards and fulfil sponsor obligations, compelled the Public Health Department to return to using a certain number of positivist methods. The ensuing inter-paradigm dialogue helped broaden the scope of evaluation and contributed to gaining a more in-depth understanding of the processes and outcomes of community mobilization.

    Title Extremely Low Vertical-emittance Beam in the Accelerator Test Facility at Kek.
    Date July 2002
    Journal Physical Review Letters
    Excerpt

    Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

    Title [the Habits and Perceptions of Participants in Water and Other Outdoor Activities in Terms of Risk Behaviors].
    Date June 2002
    Journal Canadian Journal of Public Health. Revue Canadienne De Santé Publique
    Excerpt

    The objective of this study was to explore the habits and perceptions of participants in water and other outdoor activities in terms of health risk behaviours.

    Title [behavior and Beliefs in Amateur Open Water Activities. Study of Beliefs and Attitudes with Respect to Health Risks].
    Date June 2002
    Journal Canadian Journal of Public Health. Revue Canadienne De Santé Publique
    Excerpt

    The objective of this study was to explore beliefs, attitudes and suggestions concerning effective interventions to promote the use of sun protection, the use of personal flotation devices (PFDs) and the avoidance of contact with water unfit for swimming.

    Title An Improved Gc/ms-based Procedure for the Quantitation of the Isoprostane 15-f2t-isop in Rat Plasma.
    Date December 2001
    Journal Molecular Biotechnology
    Excerpt

    This article describes a procedure for the quantitation of the isoprostane 15-F2t-IsoP (9a,11a,15S-trihydroxy-(8b)-prosta-5Z,13E-dien-1-oic acid [CAS#27415-26-5] formerly known as 8-epi-PGF2a or 8-iso-PGF2a, and also as iPF2a-III). We have combined features from several earlier methods for 15-F2t-IsoP and prostaglandins, and identified and modified those steps that may lead to poor recoveries. The resulting protocol is precise and reliable, and was validated by a blind time-course study of plasma levels in rats treated with 120 and 1200 mg CCl4/kg body weight. Plasma levels of 15-F2t-IsoP, as measured according to the procedure described above, are good indicators of acute oxidative stress as induced by CCl4. The precision of the measurements allows detection of elevated plasma 15-F2t-IsoP levels as long as 16 h after an acute exposure of 120 mg CCl4/kg body weight, and 2 h after an exposure of 1 mg CCl4/kg body weight. The results of this low-dose, pilot study suggest that this method has sufficient analytical precision to allow the detection of the small changes in plasma isoprostane levels, which result from chronic and/or lower-level exposures to agents causing oxidative stress.

    Title Exo1-dependent Mutator Mutations: Model System for Studying Functional Interactions in Mismatch Repair.
    Date August 2001
    Journal Molecular and Cellular Biology
    Excerpt

    EXO1 interacts with MSH2 and MLH1 and has been proposed to be a redundant exonuclease that functions in mismatch repair (MMR). To better understand the role of EXO1 in mismatch repair, a genetic screen was performed to identify mutations that increase the mutation rates caused by weak mutator mutations such as exo1Delta and pms1-A130V mutations. In a screen starting with an exo1 mutation, exo1-dependent mutator mutations were obtained in MLH1, PMS1, MSH2, MSH3, POL30 (PCNA), POL32, and RNR1, whereas starting with the weak pms1 allele pms1-A130V, pms1-dependent mutator mutations were identified in MLH1, MSH2, MSH3, MSH6, and EXO1. These mutations only cause weak MMR defects as single mutants but cause strong MMR defects when combined with each other. Most of the mutations obtained caused amino acid substitutions in MLH1 or PMS1, and these clustered in either the ATP-binding region or the MLH1-PMS1 interaction regions of these proteins. The mutations showed two other types of interactions: specific pairs of mutations showed unlinked noncomplementation in diploid strains, and the defect caused by pairs of mutations could be suppressed by high-copy-number expression of a third gene, an effect that showed allele and overexpressed gene specificity. These results support a model in which EXO1 plays a structural role in MMR and stabilizes multiprotein complexes containing a number of MMR proteins. A similar role is proposed for PCNA based on the data presented.

    Title Myeloperoxidase and Protein Oxidation in Cystic Fibrosis.
    Date September 2000
    Journal American Journal of Physiology. Lung Cellular and Molecular Physiology
    Excerpt

    Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), indicating local production of nitric oxide (NO. ), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO(2)(-). CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.

    Title Is the Intention to Quit Smoking Influenced by Other Heart-healthy Lifestyle Habits in 30- to 60-year-old Men?
    Date April 1998
    Journal Addictive Behaviors
    Excerpt

    The aim of this study was to analyze whether the intention to quit smoking was associated with other lifestyle habits healthy for the heart, namely a low-fat diet and regular exercise, using variables suggested by the theory of planned behavior. Self-administered postal questionnaires were sent to 3,200 men 30 to 60 years of age residing in Laval, Quebec. With a response rate of 70.9%, 671 respondents (29.6%) were smokers. A significant proportion (43%) had all three risk behaviors--smoking, a high-fat diet, and sedentariness, and 42% had two--smoking and one of the other behaviors. The remaining had a single risk behavior, namely smoking. Regression analysis suggested that a healthy diet and exercise had no significant influence on the intention to quit smoking. However, men who had a stronger intention to quit smoking than others had a more favorable attitude toward the behavior, a stronger perception of approval in achieving it on the part of important referents, stronger perceived behavioral control, and were among those who smoked fewer cigarettes per day, but had made more attempts to quit. These results can assist in designing better heart-health intervention programs for this high-risk population.

    Title Regular Exercise in 30- to 60-year-old Men: Combining the Stages-of-change Model and the Theory of Planned Behavior to Identify Determinants for Targeting Heart Health Interventions.
    Date September 1997
    Journal Journal of Community Health
    Excerpt

    The theory of planned behavior and the stages-of-change model were used to gain a clearer understanding of the factors associated with regular exercise in order to plan more effective programs in heart disease prevention. The study was conducted using a self-administered postal questionnaire sent to a sample of 2,269 men 30 to 60 years of age. Nearly a quarter (23.3%) of respondents were physically inactive, of whom 10.5% were in the precontemplation and 12.8% in the contemplation stages; 42.1% exercised less than twice a week, of whom 22.4% were in the preparation I and 19.7% in the preparation II stages. Only 34.6% were in the action stage, exercising regularly for at least 20 minutes twice a week or more with the intention of continuing to do so. Logistic regression indicated that the variables derived from the theory of planned behavior, namely attitude, subjective norm and perceived behavioral control, were differently associated with the stages of behavior. Perceived behavioral control was strongly significant in all stages. Attitude was related with stages in which individuals have intention of exercising (contemplation and preparation II). In contrast, subjective norm seemed to be associated with stages in which individuals have no intention of doing so (precontemplation and preparation I). By identifying the specific needs of sub-groups, the results can help define programs most likely to accelerate men to the stage of regular exercise, part of an effective strategy for heart health promotion in this high-risk population.

    Title [the Sale of Tobacco to Minors and the Availability of Healthy Food in Rural, Suburban and Urban Service Stations in Quebec].
    Date February 1997
    Journal Canadian Journal of Public Health. Revue Canadienne De Santé Publique
    Title Factors Influencing the Intention to Use Condoms in Quebec Sexually-inactive Male Adolescents.
    Date November 1996
    Journal The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine
    Excerpt

    The purpose of this study was to determine whether attitudes and other variables would be associated with intention to use condoms in sexually-inactive male adolescents.

    Title Determinants of Intention to Adopt a Low-fat Diet in Men 30 to 60 Years Old: Implications for Heart Health Promotion.
    Date October 1996
    Journal American Journal of Health Promotion : Ajhp
    Excerpt

    The purpose of the study was to identify the determinants of intention to have a low-fat diet in 30- to 60-year-old men.

    Title Diet and Exercise Profiles of 30- to 60-year-old Male Smokers: Implications for Community Heart Health Programs.
    Date October 1996
    Journal Journal of Community Health
    Excerpt

    The aim of this study was to estimate the prevalence of diet and exercise behaviors in middle-aged male smokers and identify their determinants of behaviors, with the ultimate goal of designing more effective interventions in a community heart health program. Self-administered, postal questionnaires produced a sample of n = 671 male smokers, 30 to 60 years of age residing in Laval, Quebec's second most populous city. Variables for the study were derived from the theory of planned behavior. Correspondence analysis explained 65% of the variance, classifying smokers into five groups based on diet and exercise behavior. Group 1, smokers with diet and exercise behaviors deemed inadequate for heart health, comprised 43% of the total. Groups 2 and 3, smokers with a diet deemed inadequate or needing improvement respectively, and Group 4, smokers with inadequate exercise, comprised 42% of the total. Group 5, smokers with neither of the other high-risk behaviors, comprised 15% of the total. Four significant variables contrasted Groups 1 to 4 with group 5: age, number of cigarettes smoked daily, and perceived behavioral control (PBC) in both diet and exercise. However, coefficients for age and smoking were weak for all groups. Coefficients for PBC in diet were high and negative only for smokers with an inadequate one. For PBC in exercise, they were high and negative only for smokers who exercised inadequately. Intervention groups based on specific deficiencies in diet and exercise behaviors were then identified. Therefore, the results suggest that smoking cessation programs may be made more effective by targeting specific sub-groups and by providing resources and opportunities to counteract the lack of perceived behavioral control in middle-aged male smokers vis-a-vis diet and exercise.

    Title [is Municipal Regulation of Tobacco Use Applicable to Laval, Quebec?].
    Date January 1996
    Journal Canadian Journal of Public Health. Revue Canadienne De Santé Publique
    Title [do Grocery Shops Help the Consumer Choose Foods That Protect the Health of the Heart? A Preliminary Study].
    Date October 1995
    Journal Canadian Journal of Public Health. Revue Canadienne De Santé Publique
    Title Behavioral Diagnosis of 30 to 60 Year-old Men in the Fabreville Heart Health Program.
    Date October 1995
    Journal Journal of Community Health
    Excerpt

    To develop effective interventions in the Fabreville Heart Health Program, a behavioral diagnosis was conducted on a sample of 1,600 men 30 to 60 years of age residing in the Fabreville district of Laval, Quebec's second most populous city. The response rate of the self-administered postal questionnaire was 73.5%. The results indicate that dietary fat consumption, smoking and a sedentary lifestyle were more prevalent among the younger respondents, particularly those less-educated. The results underline the importance of segmenting the target population so that heart health interventions can respond to the specific needs of each sub-population. Furthermore, the data seem to suggest the need to adapt educational messages to the target lifestyle habits. The results showed that in terms of diet, consumption of meat and dairy products contributed the most to fat intake. Of the 30% who were smokers, a large proportion would be reluctant to stop the habit; 20% smoked 26 cigarettes or more a day, and more than half had already tried once or more to stop. Although 60% of respondents indicated they engaged in physical activity, only 37.0% did it regularly. These results demonstrate the need to clearly target specific behaviours and subgroups in our promotion messages for a healthy heart.

    Title Influence of Attitudes on the Intention to Use Condoms in Quebec Sexually Active Male Adolescents.
    Date October 1994
    Journal The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine
    Excerpt

    The purpose of this study was to determine the influence of attitudes and other variables on the intention to use condoms in sexually active male adolescents.

    Title 20-hydroxyvitamin D2 is a Noncalcemic Analog of Vitamin D with Potent Antiproliferative and Prodifferentiation Activities in Normal and Malignant Cells.
    Date
    Journal American Journal of Physiology. Cell Physiology
    Excerpt

    20-hydroxyvitamin D(2) [20(OH)D(2)] inhibits DNA synthesis in epidermal keratinocytes, melanocytes, and melanoma cells in a dose- and time-dependent manner. This inhibition is dependent on cell type, with keratinocytes and melanoma cells being more sensitive than normal melanocytes. The antiproliferative activity of 20(OH)D(2) is similar to that of 1,25(OH)(2)D(3) and of newly synthesized 1,20(OH)(2)D(2) but significantly higher than that of 25(OH)D(3). 20(OH)D(2) also displays tumorostatic effects. In keratinocytes 20(OH)D(2) inhibits expression of cyclins and stimulates involucrin expression. It also stimulates CYP24 expression, however, to a significantly lower degree than that by 1,25(OH)(2)D(3) or 25(OH)D(3). 20(OH)D(2) is a poor substrate for CYP27B1 with overall catalytic efficiency being 24- and 41-fold lower than for 25(OH)D(3) with the mouse and human enzymes, respectively. No conversion of 20(OH)D(2) to 1,20(OH)(2)D(2) was detected in intact HaCaT keratinocytes. 20(OH)D(2) also demonstrates anti-leukemic activity but with lower potency than 1,25(OH)(2)D(3). The phenotypic effects of 20(OH)D(2) are mediated through interaction with the vitamin D receptor (VDR) as documented by attenuation of cell proliferation after silencing of VDR, by enhancement of the inhibitory effect through stable overexpression of VDR and by the demonstration that 20(OH)D(2) induces time-dependent translocation of VDR from the cytoplasm to the nucleus at a comparable rate to that for 1,25(OH)(2)D(3). In vivo tests show that while 1,25(OH)(2)D(3) at doses as low as 0.8 μg/kg induces calcium deposits in the kidney and heart, 20(OH)D(2) is devoid of such activity even at doses as high as 4 μg/kg. Silencing of CY27B1 in human keratinocytes showed that 20(OH)D(2) does not require its transformation to 1,20(OH)(2)D(2) for its biological activity. Thus 20(OH)D(2) shows cell-type dependent antiproliferative and prodifferentiation activities through activation of VDR, while having no detectable toxic calcemic activity, and is a poor substrate for CYP27B1.

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