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D Main

Publications and source records attributed to D Main.

At least 19 recordsLinked to original sources
PubMed2006

Radiation-induced untargeted germline mutations in Japanese medaka.

Radiation has been shown to increase mutation frequencies at tandem repeat loci by indirect interactions of radiation with DNA. We studied germline mutations in chronically exposed Japanese medaka (Oryzias latipes) using microsatellite loci. After screening 26 randomly selected loci among unirradiated parents and their 200 offspring, we selected seven highly mutable loci (0.5-1.0 x 10(-2) mutants per locus per gamete) and two bonus loci for further study. To determine if radiation exposure increases mutation frequencies in these loci, medaka were chronically irradiated from subadults through maturation at relatively low dose rates of 68 mGy/d. Total doses for males and females were 10.4 and 3 Gy, respectively. The mean number of mutations for the offspring of exposed families (0.149+/-0.044) was significantly higher (P=0.018) than for control families (0.080+/-0.028), indicating induction of germline mutations from chronic irradiation. This increase in the microsatellite mutation rate is greater than expected from direct interaction of radiation with DNA, suggesting indirect, untargeted mechanism(s) for mutations. This study identified microsatellite loci with a high mutational background in medaka, variation among loci and families as important variables, and demonstrated the usefulness of this fish model for studying radiation-induced germline mutations.

Alleles↗
PubMed2004

Bacterial artificial chromosome (BAC) library resource for positional cloning of pest and disease resistance genes in cassava (Manihot esculenta Crantz).

Pest and disease problems are important constraints of cassava production and host plant resistance is the most efficient method of combating them. Breeding for host plant resistance is considerably slowed down by the crop's biological constraints of a long growth cycle, high levels of heterozygosity and a large genetic load. More efficient methods such as gene cloning and transgenesis are required to deploy resistance genes. To facilitate the cloning of resistance genes, bacterial artificial chromosome (BAC) library resources have been developed for cassava. Two libraries were constructed from the cassava clones, TMS 30001, resistant to the cassava mosaic disease (CMD) and the cassava bacterial blight (CBB), and MECU72, resistant to cassava white fly. The TMS30001 library has 55, 296 clones with an insert size range of 40-150 kb with an average of 80 kb, while the MECU72 library consists of 92 160 clones and an insert size range of 25-250 kb average of 93 kb. Based on a genome size of 772 Mb, the TMS30001 and MECU72 libraries have a 5 and 11.3 haploid genome equivalents and a 95 and 99 chance of finding any sequence, respectively. To demonstrate the potential of the libraries, the TMS30001 library was screened by southern hybridization using a cassava analog (CBB1) of the Xa21 gene from rice that maps to a region containing a QTL for resistance to CBB as probe. Five BAC clones that hybridized to CBB1 were isolated and a Hind III fingerprint revealed 2-3 copies of the gene in individual BAC clones. A larger scale analysis of resistance gene analogs (RGAs) in cassava has also been conducted in order to understand the number and organization of RGAs. To scan for gene and repeat DNA content in the libraries, end-sequencing was performed on 2,301 clones from the MECU72 library. A total of 1705 unique sequences were obtained with an average size of 715 bp. Database homology searches using BLAST revealed that 458 sequences had significant homology with known proteins and 321 with transposable elements. The use of the library in positional cloning of pest and disease resistance genes is discussed.

Animals↗
PubMed2002

New genomic resources for the honey bee(Apis mellifera L.): development of a deep-coverage BAC library and a preliminary STC database.

We have constructed a bacterial artificial chromosome (BAC) library for a European honey bee strain using the cloning enzyme HindIII in order to develop resources for structural genomics research. The library contains 36,864 clones (ninety-six 384-well plates). A random sampling of 247 clones indicated an average insert size of 113 kb (range = 27 to 213 kb) and 2% empty vectors. Based on an estimated genome size of 270 Mb, this library provides approximately 15 haploid genome equivalents, allowing >99% probability of recovering any specific sequence of interest. High-density colony filters were gridded robotically using a Genetix Q-BOT in a 4 x 4 double-spotted array on 22.5-cm2 filters. Screening of the library with four mapped honey bee genomic clones and two bee cDNA probes identified an average of 21 positive signals per probe, with a range of 7-38 positive signals per probe. An additional screening was performed with nine aphid gene fragments and one Drosophila gene fragment resulting in seven of the nine aphid probes and the Drosophila probe producing positive signals with a range of 1 to 122 positive signals per probe (average of 45). To evaluate the utility of the library for sequence tagged connector analysis, 1152 BAC clones were end sequenced in both forward and reverse directions, giving a total of 2061 successful reads of high quality. End sequences were queried against SWISS-PROT, insect genomic sequence GSS, insect EST, and insect transposable element databases. Results in spreadsheet format from these searches are publicly available at the Clemson University Genomics Institute (CUGI) website in a searchable format (http://www.genome.clemson.edu/projects/stc/bee/AM__Ba/).

Animals↗
PubMed2001

Tryptophan hydroxylase gene variant and smoking behavior.

Approximately 50% of the variance in smoking behavior is attributable to genetic factors. Genes in the serotonin system are plausible candidates because of serotonin's role in mood regulation. The present study examined the association of smoking behavior with a polymorphism in the TPH gene, which codes for a rate limiting enzyme in the biosynthesis of serotonin. A polymorphism in intron 7 has been linked with a variety of traits involving poor impulse control. Participants in this study were 249 Caucasian smokers and 202 nonsmokers recruited through newspaper advertisements. Smokers completed smoking history and nicotine dependence assessments. The overall frequencies of the A- and C-allele were 42% and 58%, respectively. There was no association of TPH alleles with smoking status. However, case series analysis indicated that individuals with the A/A genotype started smoking at age 15.6 years, compared with 17.3 years among smokers with other genotypes. This association was significant in a multivariate regression model controlling for age, education, body mass index (BMI), alcohol use, and medication use. This finding is consistent with previous studies relating the A-allele to impulsive behavior and suggests that it may predispose to early smoking initiation. Future family-based studies are needed to confirm this finding. Published 2001 Wiley-Liss, Inc.

Adult↗
PubMed2001

Parental communication of BRCA1/2 genetic test results to children.

The aim of this study was to evaluate the likelihood, correlates, and psychological impact of parental communication to children of parents' BRCA1/2 genetic test results for breast cancer risk. Subjects were 133 adult members of high risk families. Sociodemographic, clinical, and psychological distress variables were assessed during a baseline telephone interview conducted prior to patient education and test result notification. Parental communication of test results to children and parental psychological distress and coping efforts were assessed 1 month post-genetic counseling and receipt of test results. Mothers (versus fathers), and persons with higher levels of baseline general distress, were significantly more likely to communicate their test results to children. Post-counseling coping efforts, both active and avoidant, were positively associated with post-counseling distress levels. However, communication of test results to children did not relate to changes in distress. In conclusion, parents with higher levels of pre-counseling general psychological distress may be more likely to communicate their genetic test results to children; however, this act does not minimize their distress and could possibly generate distress in their youngsters. Research is needed to evaluate the process and content of post-test disclosure episodes and the impact on participant, child, and family functioning.

Adaptation, Psychological↗
PubMed2001

Nicotine metabolism and CYP2D6 phenotype in smokers.

We tested the hypothesis that the polymorphic enzyme CYP2D6 is related to nicotine metabolism in 261 healthy subjects enrolling in a smoking cessation clinic. Subjects completed a questionnaire, were given dextromethorphan, and contributed a urine and blood sample. The CYP2D6 phenotype (based on a determination of dextromethorphan and metabolites in an aliquot of overnight urine) and genotype (based on characterization of CYP2D6 variant alleles by a PCR-based method on a subset) were determined. Seventeen poor metabolizers (6.5%) were observed among 261 phenotyped smokers. Nicotine and it chief metabolites, cotinine and trans-3'-hydroxycotinine were measured in the urine and adjusted for pH. All of the nicotine metabolite levels were significantly related to usual and recent smoking. Neither levels of smoking nor nicotine metabolites overall exhibited a relationship to the CYP2D6-deficient metabolizer phenotype. The ratio of nicotine:cotinine + trans-3'-hydroxycotinine, stratified by time since the last cigarette, was unrelated to gender, age, education, race (white/African American), recent alcohol or caffeine consumption, or smoking practices. Subjects in either the lowest quintile or decile metabolic ratio (ultrametabolizers) exhibited a significantly lower nicotine:cotinine + trans-3'-hydroxycotinine ratio after adjustment for recent smoking, pH, and other factors. These data suggest that the polymorphic CYP2D6 gene is not a major contributor to nicotine metabolism in tobacco smokers but may influence the disposition of nicotine in the small subset of the population who are CYP2D6 ultrametabolizers.

Adult↗
PubMed2001

Effects of coping style and BRCA1 and BRCA2 test results on anxiety among women participating in genetic counseling and testing for breast and ovarian cancer risk.

Using the monitoring process model (MPM), the authors examined the immediate effects of coping style and test results on the psychological distress of women at increased risk for breast and/or ovarian cancers. Cases selected for analysis were 107 probands and relatives of positive probands participating in genetic counseling and testing for heritable cancer risk. Specifically, the authors explored the relationships among coping style (high and low monitoring), test results (BRCA1 and BRCA2 mutation carrier and noncarrier status), and psychological distress (state anxiety). Consistent with the MPM, higher monitoring was associated with greater psychological distress while anticipating genetic test results. After test results were disclosed, greater distress was associated with testing positive for a mutation. The implications of the findings for breast and ovarian cancer patients are discussed.

Adaptation, Psychological↗
PubMed2000

Prophylactic surgery decisions and surveillance practices one year following BRCA1/2 testing.

BACKGROUND: Although genetic testing for breast cancer risk is clinically available, its impact on health-related behaviors is unknown. This study examined prophylactic surgery and surveillance behavior during the year following BRCA1/2 gene testing. METHODS: Participants were female members (n = 216) of hereditary breast-ovarian cancer families (84 mutation carriers, 83 noncarriers and 49 test decliners). In this prospective observational study, utilization of prophylactic surgery and surveillance behavior were assessed 1-year following BRCA1/2 testing. RESULTS: Only 3% of the unaffected carriers obtained prophylactic mastectomy during the 1-year follow-up period. Among the remaining females, carriers had significantly higher rates of mammography (68%) than noncarriers (44%); (OR = 7.1; C.I. = 1.36-37.1; P = 0.02). However, the adherence rate in carriers was unchanged from baseline, suggesting that this difference is attributable to a reduction in screening among noncarriers. Women ages 25-39 years were significantly less likely to obtain mammograms than those aged 40 years and older. Cancer-related distress had a positive but nonsignificant (P < 0.07) association with adherence in bivariate but not multivariate analysis. With regard to ovarian risk, only 13% of carriers obtained prophylactic oophorectomy; of the remaining female carriers, only 21% reported a CA125 and 15% reported a transvaginal ultrasound. CONCLUSION: The vast majority of BRCA1/2 carriers may not opt for prophylactic surgery, and many do not adhere to surveillance recommendations. Greater attention to risk communication and medical decision-making is warranted.

Adult↗
PubMed2000

Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence.

Individual differences in propensity to nicotine dependence appear to be mediated, in part, by genetic factors.1 The serotonin transporter gene has a functional polymorphism (5-HTTLPR) which modulates gene transcription and reuptake.2,3 A possible role in nicotine dependence is suggested by a link between 5-HTTLPR and neuroticism,4 a personality trait which has been related to smoking practices.5 In a cross-sectional study of 185 smokers, we utilized multiple linear regression modeling to examine the interacting effects of the 5-HTTLPR and neuroticism on smoking practices and nicotine dependence. Genotype was classified according to the presence or absence of the short (s) allele vs the long (l) allele of 5-HTTLPR (ie, s/s or s/l vs l/l). Models controlled for gender, age, race, and alcohol use. The 5-HTTLPR by neuroticism interaction effect was statistically significant in the models of nicotine intake (P = 0.05), nicotine dependence (P = 0.001), and smoking motivations (smoking to reduce negative mood (P = 0.01); smoking for stimulation (P = 0.01)). The results suggested that neuroticism was positively associated with these smoking practices among smokers with 5-HTTLPR S genotypes (s/s or s/l), but not among smokers with the L genotype (l/l). The 5-HTTLPR may modify the effects of neuroticism on smoking motivations and nicotine dependence. Assessment of 5-HTTLPR genotype and neuroticism may help to identify smokers who are more responsive to psychotropic medications, such as selective serotonin reuptake inhibitors (SSRIs), which are being used in smoking cessation treatment.

Adult↗
PubMed2000

Reconciling pedagogy and health sciences to promote indigenous health.

OBJECTIVES: To increase knowledge and skills regarding Indigenous learning styles. To raise awareness within the tertiary education sector that Aboriginal students learn differently and that Indigenous cultures and pedagogy have validity and strength. To examine pedagogical strategies that assist both tertiary students capacity for learning and university lecturers' delivery and evaluation of teaching and learning strategies. METHODS: A qualitative, ethnographic framework using personal observations, field and classroom experience, interviews and review of literature in the fields of education, public health and Indigenous cultural perspectives. RESULTS: Aboriginal people are the receivers of services and programs that will be delivered, in the majority of cases, by university-educated, non-Aboriginal, professional health care providers. Indigenous students face specific challenges in obtaining an effective education for working in the Aboriginal and wider community in the field of public health; the challenges relate to culture, health paradigms and community. CONCLUSION: Lecturers in health and human science courses for Aboriginal students need to both examine and appreciate the cultural constraints on learning faced by their students within the context of mainstream curriculum, and to build on the large pool of knowledge and learning styles that Aboriginal society bequeaths to Aboriginal students. IMPLICATIONS: Academics can apply the cultural differences and knowledge base of the Indigenous community as a force to promote health through learning.

Anthropology, Cultural↗
PubMed2000

Spiritual faith and genetic testing decisions among high-risk breast cancer probands.

Despite widespread access to genetic testing for the BRCA1 and BRCA2 breast cancer susceptibility genes, little is known about rates or predictors of test use among individuals from newly ascertained high-risk families who have self-referred for genetic counseling/testing. The objective of this study was to examine rates of test use within this population. In addition, we sought to determine whether spiritual faith and psychological factors influenced testing decisions. Participants were 290 women with familial breast cancer. All were offered genetic counseling and testing for alterations in the BRCA1 and BRCA2 genes. Baseline levels of spiritual faith, cancer-specific distress, perceived risk, and demographic factors were examined to identify independent predictors of whether participants received versus declined testing. The final logistic model revealed statistically significant main effects for spiritual faith [odds ratio (OR), 0.2; 95% confidence intervals (CIs), 0.1 and 0.5] and perceived ovarian cancer risk (OR, 2.4; 95% CIs, 1.3 and 4.7) and a statistically significant spiritual faith by perceived risk interaction effect. Among women who perceived themselves to be at low risk of developing breast cancer again, those with higher levels of spiritual faith were significantly less likely to be tested, compared with those with lower levels of faith (OR, 0.2; 95% CIs, 0.1 and 0.5). However, among women with high levels of perceived risk, rates of test use were high, regardless of levels of spiritual faith (OR, 1.2; 95% CIs, 0.4 and 3.0). These results highlight the role that spirituality may play in the decision-making process about genetic testing.

Adult↗
PubMed2000

Severe xerostomia in a young man.

We describe a previously healthy 24-year-old male waiter who presented with very severe xerostomia, such that he consumed an average of 7 pints of milk a day and seriously considered suicide. There were no other symptoms or signs of exocrine gland dysfunction. We discuss the differential diagnosis, investigation, and his subsequent complete response to therapy, with a review of the literature.

Adult↗
PubMed1999

Genetic testing in families with hereditary nonpolyposis colon cancer.

CONTEXT: Genetic testing for hereditary nonpolyposis colon cancer (HNPCC) is available, but the rates of acceptance of testing or barriers to participation are not known. OBJECTIVE: To investigate rates and predictors of utilization of genetic testing for HNPCC. DESIGN: Cohort study conducted between July 1996 and July 1998. SETTING: Hereditary nonpolyposis colon cancer family registry. PARTICIPANTS: Adult male and female members (n = 208) of 4 extended HNPCC families contacted for a baseline telephone interview. INTERVENTIONS: Family education and individual genetic counseling. MAIN OUTCOME MEASURE: Participant acceptance of HNPCC test results. RESULTS: Of the 208 family members, 90 (43%) received test results and 118 (57%) declined. Of 139 subjects (67%) who completed a baseline telephone interview, 84 (60%) received test results and 55 (40%) declined. Of the 84 subjects who received test results, 35 (42%) received information indicating that they had HNPCC-associated mutations and 49 (58%) that they did not. Test acceptors had higher education levels (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.49-5.61) and were more likely to have participated in a previous genetic linkage study (OR, 4.30; 95% CI, 1.84-10.10). The presence of depression symptoms significantly reduced rates of HNPCC test use (OR, 0.34; 95% CI, 0.17-0.66). Although rates of test use were identical among men and women, the presence of depression symptoms resulted in a 4-fold decrease in test use among women (OR, 0.25; 95% CI, 0.08-0.80) and a smaller, nonsignificant reduction among men (OR, 0.49; 95% CI, 0.19-1.27). CONCLUSIONS: Despite having significantly elevated risks of developing colon cancer, a relatively small proportion of HNPCC family members are likely to use genetic testing. Barriers to test acceptance may include less formal education and the presence of depression symptoms, especially among women. Additional research is needed to generalize these findings to different clinical settings and racially diverse populations.

Adult↗
PubMed1999

Reproductive health risk behavior survey of Colombian high school students.

PURPOSE: To establish rates of potentially risky sexual behaviors among Colombian adolescent students. METHODS: A total of 230 9th and 11th graders at a Colombian high school (69% of enrolled students) were anonymously surveyed about selected reproductive health behaviors using the Centers for Disease Control and Prevention's self-administered Youth Risk Behavior Survey. RESULTS: The response rate was >90%. The group was demographically representative of students. Twenty-nine percent of the group had engaged in intercourse (13% of 9th and 43% of 11th graders). Male gender [beta = 0.7873; odds ratio (OR) = 2.09; 95% confidence interval (CI) = 1.57-3.08] and increasing age (beta = 0.3413; OR = 1.41; 95% CI = 1.02-1.93) were each significantly correlated with prior sexual activity. Compared with females, males initiated intercourse at a significantly earlier age (beta = 0.284; p < .001) but did not report significantly more partners (means 2.1 vs. 1.4; chi2 = 1.25; p = .262). Forty-eight percent of respondents used contraception during their last encounter. Sixty-three percent used oral contraceptives or condoms, while the remainder used less effective methods. Contraceptive use did not correlate with gender or age. Age was significantly and positively correlated with use of alcohol prior to sexual activity (B = 1.28; OR = 3.6; 95% CI = 1.49-8.44). CONCLUSIONS: Compared with U.S. populations of similar ages, the Colombian group surveyed had fewer sexually active members, reported fewer partners, and used contraception with lower frequency.

Adolescent↗
PubMed1999

Evidence suggesting the role of specific genetic factors in cigarette smoking.

Twin studies suggest that propensity to smoke and ability to quit smoking are influenced by genetic factors. As a means of investigating the risk of smoking associated with genetic polymorphisms in the dopamine transporter (SLC6A3) and the D2 dopamine receptor (DRD2) genes, a case-control study of 289 smokers and 233 nonsmoking controls and a case series analysis of smokers were conducted. A significant effect for SLC6A3 and a significant gene-gene interaction were found in a logistic regression model, indicating that individuals with SLC6A3-9 genotypes were significantly less likely to be smokers, especially if they also had DRD2-A2 genotypes. Smokers with SLC6A3-9 genotypes were also significantly less likely to have started smoking before 16 years of age and had prior smoking histories indicating a longer period of prior smoking cessation. This study provides preliminary evidence that the SLC6A3 gene may influence smoking initiation and nicotine dependence.

Adult↗
PubMed1999

B-cell (CD79a+) lymphoma affecting the tarsal joint synovia in a sheep.

A lymphoma affecting the synovia was identified in both tarsal joints of an aged sheep. With a panel of cross-reactive antibodies specific for lambda and kappa immunoglobulin light chain, MHC class II, CD3, CD79a and the Ki-67 antigen, the neoplasm was classified as a B-cell lymphoma with uniform expression of surface membrane CD79a. This would seem to be the first report of a lymphoma affecting the synovia in a domestic animal, and the first use of the CD79a reagent on ovine tissue.

Animals↗
PubMed1998

Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene.

This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N = 231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 receptor (DRD4) gene. A significant interaction (DRD4 Genotype x Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission.

Adult↗