PubMed Health⌕ Search

Biomedical subjects

Tianxia Wu

Publications and source records attributed to Tianxia Wu.

13 recordsLinked to original sources
PubMed2006

GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence.

We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide production. After axonal injury, concentrations of BH4 rose in primary sensory neurons, owing to upregulation of GCH1. After peripheral inflammation, BH4 also increased in dorsal root ganglia (DRGs), owing to enhanced GCH1 enzyme activity. Inhibiting this de novo BH4 synthesis in rats attenuated neuropathic and inflammatory pain and prevented nerve injury-evoked excess nitric oxide production in the DRG, whereas administering BH4 intrathecally exacerbated pain. In humans, a haplotype of the GCH1 gene (population frequency 15.4%) was significantly associated with less pain following diskectomy for persistent radicular low back pain. Healthy individuals homozygous for this haplotype exhibited reduced experimental pain sensitivity, and forskolin-stimulated immortalized leukocytes from haplotype carriers upregulated GCH1 less than did controls. BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits.

Adult↗
PubMed2006

A clinical genetic method to identify mechanisms by which pain causes depression and anxiety.

BACKGROUND: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year. RESULTS: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood--the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. CONCLUSION: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts.

Anxiety Disorders↗
PubMed2006

No association between selected candidate gene polymorphisms and severe chronic periodontitis.

BACKGROUND: Chronic periodontitis (CP) risk is influenced by environmental and genetic factors. Using a case-control design, we tested for associations between CP and selected DNA sequence variations (single nucleotide polymorphisms [SNPs]) in or near genes coding for proteins that play a role in the pathogenesis of this disease. METHODS: DNA was analyzed from 219 whites who were examined clinically. Cases (N=137) were >or=35 years of age with eight or more teeth having >or=5 mm of proximal clinical attachment loss. Controls (N=82) were >or=45 years of age with minimal or no proximal attachment loss or pocketing. Nine diallelic polymorphisms (gene and SNP descriptor) were studied in subjects: cytotoxic T-lymphocyte antigen-4 (CTLA-4, 49 A>G), human beta-defensin-1 (DEFB1, 692 G>A), intercellular adhesion molecule-1 (ICAM-1, 1548 A>G), Fas ligand (fasL, -844 C>T), inducible costimulator (ICOS, 3990 G>T), interleukin-6 (IL-6, -174 G>C), cysteine-cysteine chemokine receptor-5 (CCR5, 59653 C>T), osteoprotegerin (OPG, 245 T>G), and osteopontin (OPN, 707 C>T). Genotypes were determined using an automated fluorogenic 5'-nuclease, polymerase chain reaction-based assay. Gender and smoking history (pack-years) were included as covariates in logistic regression analyses. RESULTS: Heavy smoking (>10 pack-years) and male gender were significantly associated with disease (P<0.001). For all SNPs tested, the allele frequencies and distributions of genotypes did not differ between cases and controls (P>0.05). No unadjusted or adjusted odds ratios (comparing genotypes in cases versus controls) were significantly different than 1.0 (P>0.05) under any additive, dominant, or recessive inheritance model. CONCLUSIONS: None of the SNPs tested were strongly associated with generalized severe chronic periodontitis in North American whites. A potentially more fruitful approach in future studies will be to test for associations between periodontitis and haplotype blocks constructed from either multiple SNPs in candidate gene regions or from panels of markers that span the entire genome.

Adult↗
PubMed2005

Surveillance for dental caries, dental sealants, tooth retention, edentulism, and enamel fluorosis--United States, 1988-1994 and 1999-2002.

PROBLEM/CONDITION: Dental caries is a common chronic disease that causes pain and disability across all age groups. If left untreated, dental caries can lead to pain and infection, tooth loss, and edentulism (total tooth loss). Dental sealants are effective in preventing dental caries in the occlusal (chewing) and other pitted and fissured surfaces of the teeth. Enamel fluorosis is a hypomineralization of enamel related to fluoride exposure during tooth formation (first 6 years for most permanent teeth). Exposure to fluoride throughout life is effective in preventing dental caries. This is the first CDC Surveillance Summary that addresses these conditions and practices. REPORTING PERIOD: 1988-1994 and 1999-2002. SYSTEM DESCRIPTION: The National Health and Nutrition Examination Survey (NHANES) is an ongoing survey of representative samples of the civilian, noninstitutionalized U.S. population aged >/=2 months in NHANES 1988-1994 and all ages during 1999-2002. The dental component gathered information on persons aged >/=2 years. RESULTS: During 1999-2002, among children aged 2-11 years, 41% had dental caries in their primary teeth. Forty-two percent of children and adolescents aged 6-19 years and approximately 90% of adults had dental caries in their permanent teeth. Among children aged 6-19 years, 32% had received dental sealants. Adults aged >/=20 years retained a mean of 24 of 28 natural teeth and 8% were edentulous. Among persons aged 6-39 years, 23% had very mild or greater enamel fluorosis. Disparities were noticed across all age groups, among racial/ethnic groups, persons with lower education and income, and by smoking status. From 1988-1994 to 1999-2002, four trends were observed: 1) no change in the prevalence of dental caries in primary teeth among children aged 2-11 years, 2) a reduction in prevalence of caries in permanent teeth of up to 10 percentage points among persons aged 6-19 years and up to six percentage points among dentate adults aged >/=20 years, 3) an increase of 13 percentage points in dental sealants among persons aged 6-19 years, and 4) a six percentage point reduction in total tooth loss (edentulism) among persons aged >/=60 years. INTERPRETATION: The findings of this report indicate that the dental caries status of permanent teeth has improved since the 1988-1994 survey. Despite the decrease in caries prevalence and severity in the permanent dentition and the increase in the proportion of children and adolescents who benefit from dental sealants, disparities remain. PUBLIC HEALTH ACTION: These data provide information for public health professionals in designing interventions to improve oral health and to reduce disparities in oral health, for researchers in assessing factors associated with disparities and dental caries in primary teeth, and in designing timely surveillance tools to monitor total fluoride exposure.

Adolescent↗
PubMed2005

Development of a focused microarray to assess human embryonic stem cell differentiation.

Human embryonic stem cells (hESC) must be differentiated before clinical use. In addition, the extent of contamination of undifferentiated cells and the efficiency of differentiation must also be assessed prior to clinical application. In this manuscript, we describe the development of a focused microarray that may be used to discriminate between hESC and their differentiated progeny. This array contains 755 genes including embryonic stem cell markers as well as markers of differentiation into neural, mesodermal, and endodermal phenotypes. In addition, we have included candidate genes belonging to families of cytokines, chemokines, receptors, signaling pathways, and homeodomain proteins that are likely to be important in the process of differentiation. Testing and validation of the focused array was performed using RNA from hESC, human embryoid body (hEB) outgrowths, and a human embryonal carcinoma (hEC) cell line. We have compared gene expression with negative background, GAPDH, beta-actin positive controls, and human universal RNA (hURNA), showing that such an array can rapidly distinguish between undifferentiated and differentiated hESC-derived cell populations. We expect that the described array will be extremely useful in evaluating the extent of differentiation and the state of the hESC-derived population utilized for therapeutic purposes.

Cell Differentiation↗
PubMed2005

Microsatellite polymorphisms in the epidermal growth factor receptor (EGFR) gene and the transforming growth factor-alpha (TGFA) gene and risk of oral cancer in Puerto Rico.

OBJECTIVES AND METHODS: Risks of oral cancer related to a CA microsatellite repeat polymorphism in intron 1 of the epidermal growth factor receptor (EGFR) gene and a TaqI polymorphism in the transforming growth factor-alpha (TGFA) gene were evaluated in a population-based case-control study consisting of 157 cases and 149 controls recruited in Puerto Rico. RESULTS: Carriers of > or = 16 CA repeats in EGFR showed a 1.9-fold increased risk for oral cancer (OR=1.9, 95% CI=1.0-3.5). Risks also tended to increase with decreasing number of alleles with > or = 16 CA repeats (P for trend=0.06). Our data suggested a non-significant reduction in risk for subjects heterozygous for the TGFA polymorphism (OR=0.6, 95% CI=0.2-1.3). CONCLUSIONS: The EGFR-associated risk appeared to be independent of tobacco and alcohol use and may be restricted primarily to subjects who consumed low amounts of fresh fruits and vegetables (OR=5.9, 95%CI: 2.3-15.2). These data implicate dietary and molecular targets for oral cancer prevention.

Adult↗
PubMed2005

Quantitative measures of aggressive periodontitis show substantial heritability and consistency with traditional diagnoses.

BACKGROUND: Aggressive periodontitis (AgP) research nearly always classifies subjects into traditional discrete categories of localized or generalized, based upon degree of attachment loss (AL) and types of affected teeth. Since AL is continuous and quantitative, however, useful information is lost. We developed quantitative measures of AgP, compared these to traditional methods, and estimated heritabilities in families. METHODS: We examined 237 healthy, 169 localized AgP, and 204 generalized AgP subjects. We used the site of maximum AL of each tooth to calculate means for each subject for different groups of teeth. We also applied principal components analysis (PCA) to condense variation among 28 teeth into three orthogonal (uncorrelated) variables. We used discriminant function analysis (DFA) to evaluate how well the quantitative measures match with traditional classifications. Quantitative trait heritabilities were estimated by variance components. RESULTS: PCA clustered first molars, incisors, and the other teeth into three groups. DFA showed that quantitative measures classified subjects consistent with traditional methods (87% to 94% agreement). Heritabilities ranged from 13.7% (P = 0.10) to 30.0% (P = 0.008) for quantitative measures, with highest values obtained for first molars. A combination of the principal component variables most heavily weighted on first molars and incisors gave the best model of disease susceptibility, with good separation of healthy versus diseased subjects, independent of disease extent or severity. CONCLUSIONS: Quantitative measures may provide improved precision and power for many kinds of periodontal research. Our finding of significant heritability supports their use in gene mapping studies of AgP susceptibility.

Acute Disease↗
PubMed2003

Insulin-like growth factor II receptor gene-167 genotype increases the risk of oral squamous cell carcinoma in humans.

Our purpose was to evaluate inherited short tandem repeat polymorphisms of the insulin-like growth factor II receptor gene (IGF2R) in oral cancer risk. The 197 individuals that consented to participate in a hospital-based, case-control study were interviewed with a structured questionnaire and provided blood and saliva. DNA was extracted for genotyping using a PCR-based method. Odds ratios were calculated using multivariate logistic regression. Subjects carrying the heterozygous 167-bp IGF2R genotype had a 2.7-fold higher risk of oral cancer compared with subjects with other genotypes (odds ratio = 2.7, 95% confidence interval: 1.16-6.48), controlling for major confounders. Our results suggest that genetic variation of IGF2R may influence significantly the risk of oral cancer.

Adult↗
PubMed2002

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk.

We investigated effects on oral cancer (OC) risk of an interaction between a single nucleotide polymorphism (SNP) in the alcohol dehydrogenase 3 (ADH3) gene and alcohol consumption levels using a hospital-based study of 93 cases and 99 controls conducted in Athens, Greece. This SNP affects ethanol metabolism in vitro and appeared to interact with alcohol consumption in a previous OC study. We also evaluated a SNP in CYP2E1, another gene involved in ethanol metabolism, reported to be associated with OC risk in a European population. Data on genotypes and risk factors obtained from interviews were analyzed using multivariate logistic regression, accounting for potential confounders. No overall (marginal) association was found between OC risk and ADH3 genotypes. An interaction between ADH3 genotypes and alcohol consumption levels, however, was suggested. In non-drinkers, the ADH3(1-1) genotype has higher risk than ADH3(1-2) or ADH3(2-2) genotypes, but for subjects consuming alcohol, lower risk was observed for ADH3. We fit a logistic regression model to estimate the increase in OC risk associated with each alcohol drink consumed per week. We estimated that OC risk increased by 31.5% per drink/week for the ADH3(2-2) genotype, 4.1% for the ADH3(1-2) genotype and 1.6% for the ADH3(1-1) genotype. Evidence of genotype-environment interaction was suggestive (p = 0.048, Wald chi p = 0.145, likelihood ratio). This finding is opposite to that reported for a population in Puerto Rico, where the ADH3(1-1) genotype seemed more sensitive to ethanol exposure. In Greece, genetic variation at the CYP2E1 SNP is almost entirely absent, with only 1 case and 1 control heterozygous for the variant. By contrast, in a population in France where an OC association was reported, the frequency of CYP2E1 heterozygotes was 5% in controls and 9% in OC cases. These findings illustrate the importance of replicating SNP associations both within and between different racial and ethnic groups and geographic regions.

Alcohol Dehydrogenase↗
PubMed2002

Use of US birth certificate data to estimate the risk of maternal cigarette smoking for oral clefting.

OBJECTIVE: The purpose of this study was to evaluate the relationship between maternal cigarette smoking and the risk of having an offspring with an oral cleft. DESIGN: This was a large population-based, matched case-control study derived from the United States Natality database for 1997. SUBJECTS: The sample consisted of 2029 cases with non-syndromic oral clefts and 4050 non-malformed controls. Controls were matched to cases on mother's and father's race and child's sex, county of birth, and month of birth. This sample was selected from a total of 3,093,821 births in the United States, which represents 80% of all births in this country during 1997. RESULTS: The association between maternal cigarette smoking and oral clefts in the offspring was close to the null (odds ratio 1.16; 95% confidence interval (CI) 1.01 to 1.33; one-sided Fisher exact test p =.0207). The comparison and pooling of results to those of a similar study that used the U.S. Natality database for 1996 resulted in a common Mantel-Haenszel odds ratio of 1.33 (95% CI 1.21 to 1.46). The dose-response analysis was slightly significant for all levels of maternal smoking. CONCLUSION: This large study confirms that smoking during pregnancy is only a minor risk factor for oral clefting in the offspring.

Adult↗
PubMed2002

Prenatal and perinatal factors associated with isolated oral clefting.

OBJECTIVE: To describe medical service utilization and maternal morbid conditions of women who carry offspring with oral clefts (OCs), to describe maternal and offspring complications during birth, and to evaluate postnatal characteristics of their newborns with isolated OCs. METHODS: Two thousand four hundred thirty-seven patients with isolated OCs and 4871 unaffected matched controls meeting inclusion criteria were selected from the U.S. Natality database for 1997. Matching variables were mother's and father's race and child's race, sex, county of birth, and month of birth. Patients and controls were compared in terms of maternal demographic characteristics, gestational complications, physical characteristics of the newborns, maternal exposure to potential risk factors, and adequacy of prenatal care. RESULTS: Although the quality of care was very good in both groups, low gestational age, low birth weight, and low 5-minute Apgar score are more frequent among newborns with OCs than in unaffected controls. Mothers of offspring with OCs are at increased risk, compared with mothers of controls, of having hydramnios or oligohydramnios, eclampsia, and abruptio placenta. Obstetric procedures, such as amniocentesis, electronic fetal monitoring, induction of labor, tocolysis, and ultrasound, and repeat cesarean deliveries are more frequent among mothers of patients than those of controls. At birth, newborns with isolated OCs are at risk of having hyaline membrane disease and of requiring assisted ventilation, independently of gestational age. CONCLUSION: The results of this large population-based, case-control study suggest that the presence of an OC in the offspring is associated with increased risk for prenatal and perinatal complications in the mother.

Abruptio Placentae↗
PubMed2001

Mapping a gene for neuropathic pain-related behavior following peripheral neurectomy in the mouse.

Total hindpaw denervation in rodents elicits an abnormal behavior of licking, scratching and self-injury of the anesthetic limb ("autotomy"). Since the same denervation produces phantom limb pain and anesthesia dolorosa in humans, autotomy has been used as a model of human neuropathic pain. Autotomy is an inherited trait in rodents, attributable to a few genes of major effect. Here we used recombinant inbred (RI) mouse lines of the AXB-BXA RI set to map a gene for autotomy. Autotomy levels following unilateral sciatic and saphenous nerve section were scored daily for 36 days, using a standardized scale, in all 23 RI lines available for this set. We used a genetic map of 395 marker loci and a permutation-based statistical method for categorical data to assess the statistical significance of mapping results. We identified a marker on chromosome 15 with statistical support (P=0.0003) in the range considered significant for genome-wide scans in the mouse. Several genes located in this chromosomal region encode for neural functions related to neuropathic pain and may indicate targets for development of novel analgesics.

Animals↗