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Biomedical subjects

Ke Xu

Publications and source records attributed to Ke Xu.

At least 37 records · Page 2Linked to original sources
PubMed2006

Catechol-O-methyltransferase Val158Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups.

OBJECTIVE: A single-nucleotide polymorphism of the gene coding for catechol-O-methyltransferase (COMT Val(158)Met) is associated with prefrontal-dependent task performance in schizophrenia. We evaluated the relationship of the COMT genotype with diagnostic status and cognitive performance in schizotypal personality disorder. METHODS: Unmedicated outpatients with schizotypal personality disorder (SPD; n = 67) and non-schizotypal personality disorder (NSPD; n = 154) by DSM-III-R, and normal control (NC; n = 60) participants were genotyped at the COMT Val(158)Met locus. Of these, 98 Caucasians (23 SPD, 52 NSPD and 23 NC) performed a brief neurocognitive battery: Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Visuospatial Working Memory (DOT) and Visual Delayed Recall (Wechsler Memory Scale Visual Reproduction, WMS-VR). RESULTS: Allele distribution was not significantly different in the full sample (by chi(2)) for the SPD group compared with either the NC or combined NC/NSPD groups. In analyses of variance of Caucasian individuals, the SPD group performance met or approached significantly worse performance than NC, NSPD or both groups, on the PASAT, CVLT and WMS-VR. In regression analyses of cognitive performance, the COMT genotype was significantly associated with performance on WCST and PASAT, independent of diagnosis, with the Val/Val genotype associated with the worse performance. CONCLUSIONS: (1) Allelic variation in COMT activity is unrelated to the diagnosis of SPD in this sample. (2) Individuals with SPD exhibit multiple deficits in prefrontal and temporal lobe-dependent tasks. (3) The COMT genotype is related to performance on prefrontal cortex-dependent tasks and may contribute to the deficit in prefrontal-dependent memory processes in SPD as it does in schizophrenia.

Adult↗
PubMed2006

DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients.

OBJECTIVE: All antipsychotics act on the dopamine D(2) receptor. The present study extends prior pharmacogenetic investigations of the D(2) receptor gene (DRD2) by examining, in first-episode schizophrenia patients, promoter region variation as a predictor of response time to two first-line atypical antipsychotics. METHOD: Patients experiencing their first episode of schizophrenia (N=61) were genotyped for two DRD2 promoter region polymorphisms (A-241G and -141C Ins/Del) and were randomly assigned to receive 16 weeks of treatment with either risperidone or olanzapine. Time until sustained response (two consecutive ratings without significant positive symptoms) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves. RESULTS: Relative to wild type homozygotes, G carriers (A-241G) exhibited a significantly faster time until response, whereas -141C Del carriers took a significantly longer time to respond. Diplotype analysis revealed similar results. CONCLUSIONS: These findings suggest that variation in the D(2) receptor gene can, in part, explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia.

Adolescent↗
PubMed2006

Using ancestry-informative markers to define populations and detect population stratification.

A serious problem with case-control studies is that population subdivision, recent admixture and sampling variance can lead to spurious associations between a phenotype and a marker locus, or indeed may mask true associations. This is also a concern in therapeutics since drug response may differ by ethnicity. Population stratification can occur if cases and controls have different frequencies of ethnic groups or in admixed populations, different fractions of ancestry, and when phenotypes of interest such as disease, drug response or drug metabolism, also differ between ethnic groups. Although most genetic variation is inter-individual, there is also significant inter-ethnic variation. The International HapMap Project has provided allele frequencies for approximately three million single nucleotide polymorphisms (SNPs) in Africans, Europeans and East Asians. SNP variation is greatest in Africans. Statistical methods for the detection and correction of population stratification, principally Structured Association and Genomic Control, have recently become freely available. These methods use marker loci spread throughout the genome that are unlinked to the candidate locus to estimate the ancestry of individuals within a sample, and to test for and adjust the ethnic matching of cases and controls. To date, few case-control association studies have incorporated testing for population stratification. This paper will focus on the debate about the quantity and methods for selection of highly informative marker loci required to characterize populations that vary in substructure or the degree of admixture, and will discuss how these theoretically desirable approaches can be effectively put into practice.

Case-Control Studies↗
PubMed2006

Imaging genomics applied to anxiety, stress response, and resiliency.

Anxiety and stress response/resiliency are heritable traits central to the etiology of multiple psychiatric diseases, but efforts to identify genetic variation influencing this broad domain of neurobiological function are hampered by the coarseness of the phenotypic measures and the effects of environmental factors. Neuroimaging offers a powerful approach for assessing functional neuronal activity. Neurophysiological measures can serve as intermediate phenotypes more directly linked to small gene effects, compared with behavioral end points of neural dysfunction. Imaging genomics is a relatively new research area that is concerned with linking functional gene variants and brain information processing. Here, we will focus on processes affected by anxiety and stress. Neuroimaging has been combined with genetic analysis to reveal genetic effects of functional variants of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) genes on brain response to stressful stimuli. The low-expressing allele of the 5-HTT promoter polymorphism (HTTLPR) is associated with anxiety and with greater amygdala and other regional responses to emotional. The COMT Met158 allele leads to lower COMT activity and has also been associated with anxiety, and the effect of this gene is apparently additive with HTTLPR. Individuals with Met158 genotypes are more sensitive to pain stress and, as shown by C11 Carfentanil imaging, have diminished ability to upregulate opioid release after pain/stress. These results suggest that functional variants of 5-HTT and COMT impact brain functions involved in stress and anxiety.

Adaptation, Psychological↗
PubMed2006

To retain or remove user fees?: reflections on the current debate in low- and middle-income countries.

Many low- and middle-income countries continue to search for better ways of financing their health systems. Common to many of these systems are problems of inadequate resource mobilisation, as well as inefficient and inequitable use of existing resources. The poor and other vulnerable groups who need healthcare the most are also the most affected by these shortcomings. In particular, these groups have a high reliance on user fees and other out-of-pocket expenditures on health which are both impoverishing and provide a financial barrier to care. It is within this context, and in light of recent policy initiatives on user fee removal, that a debate on the role of user fees in health financing systems has recently returned. This paper provides some reflections on the recent user fees debate, drawing from the evidence presented and subsequent discussions at a recent UNICEF consultation on user fees in the health sector, and relates the debate to the wider issue of access to adequate healthcare. It is argued that, from the wealth of evidence on user fees and other health system reforms, a broad consensus is emerging. First, user fees are an important barrier to accessing health services, especially for poor people. They also negatively impact on adherence to long-term expensive treatments. However, this is offset to some extent by potentially positive impacts on quality. Secondly, user fees are not the only barrier that the poor face. As well as other cost barriers, a number of quality, information and cultural barriers must also be overcome before the poor can access adequate health services. Thirdly, initial evidence on fee abolition in Uganda suggests that this policy has improved access to outpatient services for the poor. For this to be sustainable and effective in reaching the poor, fee removal needs to be part of a broader package of reforms that includes increased budgets to offset lost fee revenue (as was the case in Uganda). Fourthly, implementation matters: if fees are to be abolished, this needs clear communication with a broad stakeholder buy-in, careful monitoring to ensure that official fees are not replaced by informal fees, and appropriate management of the alternative financing mechanisms that are replacing user fees. Fifthly, context is crucial. For instance, immediate fee removal in Cambodia would be inappropriate, given that fees replaced irregular and often high informal fees. In this context, equity funds and eventual expansion of health insurance are perhaps more viable policy options. Conversely, in countries where user fees have had significant adverse effects on access and generated only limited benefits, fee abolition is probably a more attractive policy option. Removing user fees has the potential to improve access to health services, especially for the poor, but it is not appropriate in all contexts. Analysis should move on from broad evaluations of user fees towards exploring how best to dismantle the multiple barriers to access in specific contexts.

Community Health Services↗
PubMed2006

[Clinical observation on effect of danzhi xiaoyao powder in treating depression].

OBJECTIVE: To observe the effect and side effect of Danzhi Xiaoyao powder (DXP) in treating depression. METHODS: A randomized controlled and double-blinded study was conducted in 63 cases of depression by divided them into the western medicine group (WMG, 31 cases) treated with maprotiline, and the Chinese medicine group (CMG, 32 cases) treated with DXP. The effect of therapy was evaluated before and at the 2nd, 4th and 6th week of the treatment with Hamilton's depressive scale (HAMD), self-rating depression scale (SDS), self-rating anxiety scale (SAS) and the scale for TCM syndrome and symptom differentiation (TCM-SSD), and the side-effect of therapy was assessed with Asberg side-effect scale as well. RESULTS: There was no significant difference between the two groups in scores of HAMD, SDS, SAS, and TCM-SSD. The markedly effective rate in CMG was 84% and in WMG 87%, showed no significance between them (P > 0.05). The scores of HAMD, SDS and SAS of both groups were remarkably lowered after therapy (P < 0.05). However, the score of Asberg in CMG was lower than that in WMG (P < 0.05). CONCLUSION: DXP shows the effect equivalent to that of maprotiline, but with obviously less side-effect.

Adult↗
PubMed2006

[Removal of metal ions and dissolved organic compounds in the aqueous solution via micellar enhanced ultrafiltration].

With continuing stringent environmental regulation, the traditional techniques are incapable of reducing the concentration of dissolved organics and heavy metals to the levels required by law or prohibitively expensive. Surfactant-based separation process such as micellar-enhanced ultrafiltration has been extensively proposed. Micellar-enhanced ultrafiltration has been demonstrated to be effective in removal of heavy metals and/or organic contaminants from wastewater stream. The process can be low energy cost and easily included in a whole process. Micellar-enhanced ultrafiltration has been shown to be a promising method for the removal of low-levelsof heavy metal ions and organic compounds from industrial effluents. This paper introduces the working mechanism, main factors of MEUF and the selection of surfactant and membrane. The lasted study progress on the application of micellar-enhanced ultrafiltration is reviewed. The recovery and reuse of surfactant from the retentate and permeate are also discussed.

Metals, Heavy↗
PubMed2006

[Study on the coinfection of Hantavirus and Orientia tsutsugamushi in tissue cell culture].

OBJECTIVE: To investigate the possibility of Hantavirus (HV) and Orientia tsutsugamushi (Ot) coinfection in their hosts. METHODS: HV and Ot were used to infect Vero E6 cells cultured in vitro singly, simultaneously or successively. Genes of HV and Ot were identified in different generation cells with RT-PCR. RESULTS: Five experiment groups of infected Vero E6 cells were tested, the results were as follows: HV and Ot were both positive in infected Vero E6 cells passaged 2 times and the positive rate increased following the passaged times in HV and Ot infection groups, simultaneously or successively. However, in the groups which were infected with HV and Ot separately, the gene of HV or Ot could be detected in infected Vero E6 cells passaged only once and the positive rate increased following the times of the passaged. The positive rate was higher in the singly infected groups than in those infected simultaneously or successively. CONCLUSION: Coinfection of HV and Ot did exist in the hosts while HV and Ot could inhibit each other in the initial infection stage.

Animals↗
PubMed2005

Ground-state equilibrium thermodynamics and switching kinetics of bistable [2]rotaxanes switched in solution, polymer gels, and molecular electronic devices.

We report on the kinetics and ground-state thermodynamics associated with electrochemically driven molecular mechanical switching of three bistable [2]rotaxanes in acetonitrile solution, polymer electrolyte gels, and molecular-switch tunnel junctions (MSTJs). For all rotaxanes a pi-electron-deficient cyclobis(paraquat-p-phenylene) (CBPQT4+) ring component encircles one of two recognition sites within a dumbbell component. Two rotaxanes (RATTF4+ and RTTF4+) contain tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) recognition units, but different hydrophilic stoppers. For these rotaxanes, the CBPQT4+ ring encircles predominantly (>90 %) the TTF unit at equilibrium, and this equilibrium is relatively temperature independent. In the third rotaxane (RBPTTF4+), the TTF unit is replaced by a pi-extended analogue (a bispyrrolotetrathiafulvalene (BPTTF) unit), and the CBPQT4+ ring encircles almost equally both recognition sites at equilibrium. This equilibrium exhibits strong temperature dependence. These thermodynamic differences were rationalized by reference to binding constants obtained by isothermal titration calorimetry for the complexation of model guests by the CBPQT4+ host in acetonitrile. For all bistable rotaxanes, oxidation of the TTF (BPTTF) unit is accompanied by movement of the CBPQT4+ ring to the DNP site. Reduction back to TTF0 (BPTTF0) is followed by relaxation to the equilibrium distribution of translational isomers. The relaxation kinetics are strongly environmentally dependent, yet consistent with a single electromechanical-switching mechanism in acetonitrile, polymer electrolyte gels, and MSTJs. The ground-state equilibrium properties of all three bistable [2]rotaxanes were reflective of molecular structure in all environments. These results provide direct evidence for the control by molecular structure of the electronic properties exhibited by the MSTJs.

Journal Article↗
PubMed2005

Understanding the impact of eliminating user fees: utilization and catastrophic health expenditures in Uganda.

There is currently considerable discussion between governments, international agencies, bilateral donors and advocacy groups on whether user fees levied at government health facilities in poor countries should be abolished. It is claimed that this would lead to greater access for the poor and reduce the risks of catastrophic health expenditures if all other factors remained constant, though other factors rarely remain constant in practice. Accordingly, it is important to understand what has actually happened when user fees have been abolished, and why. All fees at first level government health facilities in Uganda were removed in March 2001. This study explores the impact on health service utilization and catastrophic health expenditures using data from National Household Surveys undertaken in 1997, 2000 and 2003. Utilization increased for the non-poor, but at a lower rate than it had in the period immediately before fees were abolished. Utilization among the poor increased much more rapidly after the abolition of fees than beforehand. Unexpectedly, the incidence of catastrophic health expenditure among the poor did not fall. The most likely explanation is that frequent unavailability of drugs at government facilities after 2001 forced patients to purchase from private pharmacies. Informal payments to health workers may also have increased to offset the lost revenue from fees. Countries thinking of removing user charges should first examine what types of activities and inputs at the facility level are funded from the revenue collected by fees, and then develop mechanisms to ensure that these activities can be sustained subsequently.

Adolescent↗
PubMed2005

Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression.

Differentiation induction is an effective therapy for acute promyelocytic leukemia (APL), which dramatically responds to all-trans-retinoic acid (ATRA). Recent studies have indicated that combinatorial use of retinoid and nonretinoid compounds, such as histone deacetylase inhibitors, arsenics, and PKA agonists, has higher therapeutic value in this disease and potentially in other malignancies. In a screen of 370 compounds, we identified benzodithiophene analogues as potent enhancers of ATRA-induced APL cell differentiation. These effects were not associated with changes in global histone acetylation and, for the most potent compounds, were exerted at very low nanomolar concentrations, and were paralleled by enhancement of some, but not all, ATRA-modulated gene expressions. Investigating the mechanism underlying the effects of these drugs on ATRA-induced APL cell differentiation, we have shown that benzodithiophenes enhance ATRA-mediated dissociation and association of corepressor N-CoR and coactivator p300 acetyltransferase, respectively, with retinoic acid receptor (RAR) alpha proteins. These data suggest that benzodithiophenes act at the level of receptor activation, possibly by affecting posttranslational modification of the receptor (and/or coregulators), thus leading to an enhancement in ATRA-mediated effects on gene expression and APL cell differentiation. Given the specificities of these low benzodithiophene concentrations for PML-RARalpha and RARalpha, these drugs may be useful for combinatorial differentiation therapy of APL and possibly other acute myelogenous leukemia subtypes in which the overall ATRA signaling is suppressed.

Cell Differentiation↗
PubMed2005

Effects of pH, salt, and macromolecular crowding on the stability of FK506-binding protein: an integrated experimental and theoretical study.

Environmental variables can exert significant influences on the folding stability of a protein, and elucidating these influences provides insight on the determinants of protein stability. Here, experimental data on the stability of FKBP12 are reported for the effects of three environmental variables: pH, salt, and macromolecular crowding. In the pH range of 5-9, contribution to the pH dependence of the unfolding free energy from residual charge-charge interactions in the unfolded state was found to be negligible. The negligible contribution was attributed to the lack of sequentially nearest neighboring charged residues around groups that titrate in the pH range. KCl lowered the stability of FKBP12 and the E31Q/D32N double mutant at small salt concentrations but raised stability after approximately 0.5 M salt. Such a turnover behavior was accounted for by the balance of two opposing types of protein-salt interactions: the Debye-Hückel type, modeling the response of the ions to protein charges, favors the unfolded state while the Kirkwood type, accounting for the disadvantage of the ions moving toward the low-dielectric protein cavity from the bulk solvent, disfavors the unfolded state. Ficoll 70 as a crowding agent was found to have a modest effect on protein stability, in qualitative agreement with a simple model suggesting that the folded and unfolded states are nearly equally adversely affected by macromolecular crowding. For any environmental variable, it is the balance of its effects on the folded and unfolded states that determines the outcome on the folding stability.

Ficoll↗
PubMed2005

Isolation of transposon mutants from Azospirillum brasilense Yu62 and characterization of genes involved in indole-3-acetic acid biosynthesis.

The molecular genetics of indole-3-acetic (IAA) synthesis and regulation in Azospirillum brasilense was investigated in this study. Tn5 mutagenesis was performed and five mutants with decreased IAA production were isolated. Five Tn5-inserted genes from these mutants were cloned and sequenced. Four genes were reported for the first time to be involved in IAA production, namely, atrA, ftsA, omaA and aldA that code for GntR-family transcriptional regulator, iron-binding protein component of ABC-type Fe(3+) transport system, outer membrane protein, and aldehyde dehydrogenase, respectively. In addition, two genes atrB and atrC, with predicted proteins that showed high homology to aminotransferases, were cloned from the downstream of atrA in this bacterium. Studies also showed that complementation of atrA, ftsA and omaA were able to restore the IAA production of the corresponding IAA(-) mutants. Comparison of Fe(3+) concentrations in culture supernatants of the wild-type strain, the ftsA mutant and the complemented strain revealed that the iron-uptake ability of the ftsA mutant was highly reduced. This result also points to the necessity of iron as a metal ion in IAA synthesis. Statistical analysis showed no significant difference in the IAA accumulated in cells between the omaA mutant and the wild-type strain, suggesting the omaA might not affect IAA secretion but be involved in IAA production in other unknown ways.

Azospirillum brasilense↗
PubMed2005

BDNF variation and mood disorders: a novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects.

The brain-derived neurotrophic factor (BDNF) gene is critical for neuronal function and survival, and is likely to be important in psychiatric disorders. In this study, we used single-nucleotide polymorphism (SNP) discovery, functional analyses, and genetic association studies to better understand the potential role of BDNF sequence variation in behavior. Screening 480 unrelated individuals for SNPs and genotyping was performed in US Caucasian, American Indian, and African American populations. Lifetime DSM-III-R psychiatric diagnoses were assigned and the Tridimensional Personality Questionnaire (TPQ) was administered to measure anxious temperament (harm avoidance (HA)) and novelty seeking (NS). A novel SNP (-281 C>A) in promoter 1 was discovered that had decreased DNA binding in vitro and decreased basal reporter gene activity in transfected rat hippocampal neurons. The frequency of the -281 A allele was 0.03 in a Caucasian sample, but was virtually absent in other populations. Association analyses in a community-based sample showed that individuals with the -281 A allele (13 heterozygotes) had lower TPQ HA (F=4.8, p<0.05). In contrast, the Met 66 allele was associated with increased HA (F=4.1, p=0.02) and was most abundant in individuals with both anxiety disorders and major depression (p<0.05). Among the Val66Val homozygotes, individuals who were -281 CA heterozygotes had significantly lower HA than the -281 CC homozygotes (p<0.01). Our results suggest that in this population, the low activity -281 A allele may be protective against anxiety and psychiatric morbidity, whereas Met 66 may be a risk allele.

Adult↗
PubMed2005

Association of COMT Val158Met genotype with executive functioning following traumatic brain injury.

Catechol-O-methyltransferase (COMT) is thought to functionally modulate dopamine neurons, thus likely influencing frontal-executive functioning. High enzyme activity (COMT Val) and low enzyme activity (COMT Met) are functional polymorphisms resulting from a G to A transition in exon 4 (codon 158) of the human COMT gene. Decreased cortical dopamine should result in poorer executive functioning. Therefore, the authors hypothesized that individuals with traumatic brain injury (TBI) and the low enzyme activity polymorphism would perform better on tests of executive functioning than individuals with the high enzyme activity polymorphism. One hundred thirteen individuals referred to the Defense and Veterans Brain Injury Center underwent a comprehensive TBI evaluation and were genotyped for the COMT polymorphism. Comparison of mean differences among the COMT genotype groups for several measures of aspects of executive functioning was conducted using analysis of variance (ANOVA) with adjustment for multiple comparisons. Homozygotes for the higher activity allele made more perseverative responses on the Wisconsin Card Sorting Test, while homozygotes for the lower activity allele had the least number of perseverative responses. While it cannot be determined whether TBI influenced the association of COMT Val158Met to executive functioning, these data extend the known relationship of genotype to executive performance seen in healthy comparison subjects and individuals with schizophrenia to individuals with TBI.

Adult↗