Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Cigarette smoke creates a molecular field of injury in epithelial cells that line the respiratory tract. We hypothesized that transcriptome sequencing (RNA-seq) will enhance our understanding of the field of molecular injury in response to tobacco smoke exposure and lung cancer pathogenesis by identifying gene expression differences not interrogated or accurately measured by microarrays. We sequenced the high- molecular weight fraction of total RNA (>200 nt) from pooled bronchial airway epithelial cell brushings (n = 3 patients per pool) obtained during bronchoscopy from healthy never smoker (NS) and current smoker (S) volunteers and smokers with (C) and without ( C) lung cancer undergoing lung nodule resection surgery. RNA-seq libraries were prepared using two distinct approaches, one capable of capturing non-polyadenylated RNA (the prototype NuGEN Ovation RNA-seq protocol) and the other designed to measure only polyadenylated RNA (the standard Illumina mRNA-seq protocol) followed by sequencing generating approximately 29 million 36 nt reads per pool and approximately 22 million 75 nt paired-end reads per pool, respectively. The NuGEN protocol captured additional transcripts not detected by the Illumina protocol at the expense of reduced coverage of polyadenylated transcripts, while longer read lengths and a paired-end sequencing strategy significantly improved the number of reads that could be aligned to the genome. The aligned reads derived from the two complementary protocols were used to define the compendium of genes expressed in the airway epithelium (n = 20,573 genes). Pathways related to the metabolism of xenobiotics by cytochrome P450, retinol metabolism, and oxidoreductase activity were enriched among genes differentially expressed in smokers, whereas chemokine signaling pathways, cytokine-cytokine receptor interactions, and cell adhesion molecules were enriched among genes differentially expressed in smokers with lung cancer. There was a significant correlation between the RNA-seq gene expression data and Affymetrix microarray data generated from the same samples (P < 0.001); however, the RNA-seq data detected additional smoking- and cancer-related transcripts whose expression was were either not interrogated by or was not found to be significantly altered when using microarrays, including smoking- related changes in the inflammatory genes SIOOA8 and SIOOA9 and cancer-related changes in MUC5AC and secretoglobin (SCGB3Al). Quantitative realtime PCR confirmed differential expression of select genes and non-coding RNAs within individual samples. These results demonstrate that transcriptome sequencing has the potential to provide new insights into the biology of the airway field of injury associated with smoking and lung cancer. The measurement of both coding and non-coding transcripts by RNA-seq has the potential to help elucidate mechanisms of response to tobacco smoke and to identify additional biomarkers of lung cancer risk and novel targets for chemoprevention. / 2031-01-01

Twenty-one 8-14 kg adult male stumptailed macaques, Macaca arctoides, were fed a standard laboratory diet and divided into 3 groups. The high-dose group and low-dose group were exposed to cigarette smoke at the human equivalent of 3 packs and 1 pack per day, respectively, 7 days per week, for 3-5 years. Eight animals served as cage and sham controls. Peak blood carboxyhemoglobin (COHb) levels measured immediately after smoking showed levels of 0.5 ± 0.1%, 3.6 ± 1.0%, and 5.7 ± 2.8% for. sham controls, low, and high dose smokers, respectively. Hemoglobin and hematocrit values were 2-7% higher (N.S. to P < 0.05) for smoking groups, presumably as a consequence of chronically elevated COHb levels. No significant differences were seen in total plasma cholesterol and lipoprotein cholesterol concentration measured at four intervals over a period of one year. We conclude from these data that, while fed a low fat diet, chronic cigarette smoke inhalation fails to alter plasma lipoprotein levels in this animal model.

The purpose of this study was to explore the relationships among the following perspectives: perception of family disharmony, parent-child relationships, disharmonious family relationships, and adolescent cigarette smoking. Participants from a southeastern university reported about whether they smoke daily, weekly, monthly, never, or no longer smoke. The independent variable was smoking status of participants. Four to eight rating scales served as dependent variables for the three perspectives. Independent groups (smoking status) multivariate analyses of variance with unequal cell sizes were performed on the rating scale measures. Because none of the comparison tests were significant, the results were interpreted to suggest that no association between perception of family disharmony, parent-child relationships, disharmonious family relationships, and adolescent cigarette smoking exists.

Introduction: Currently there are approximately 1.2 million people in the United States living with HIV and it is estimated that 25.6% of HIV-positive adults suffer from depression. The purpose of this study is to examine the contribution of depression on substance use and medication adherence specifically among HIV-positive adult Georgians receiving medical care for HIV. Methods: Secondary data with a probability sample of 608 HIV-positive adults who took part in the 2009-2012 Georgia Medical Monitoring Project (MMP) were analyzed. Descriptive analysis and multivariate logistic regression models were conducted to assess relationships between depression with current cigarette smoking, injection drug use, other non-injection drug use, and medication adherence, adjusting for sociodemographic covariates (age, gender, race, and education). All analyses accounted for non-response and complex sampling design and were performed using SAS 9.2 (Cary, NC). Results: Among HIV-positive adults in Georgia, approximately 9.2% met the criteria for major depression; 15.2% of women and 6.9% of men had major depression. Heterosexual adults also had a higher percentage of major depression (11.9%) compared to adults who identified as bisexual (8.3%) or homosexual (6.1%). Major depression was also highest among young adults (17.1%) and adults with high school diploma or GED (13.0%). Major depression was associated with a greater odds of current cigarette smoking (3.04; 95% CI: 1.48, 6.23); injection drug use (5.62; 95% CI: 0.96, 32.81), and other non-injection drug use (2.17; 95% CI: 1.10, 4.25), after adjusting for sociodemographic variables. Major depression was also associated with a greater odds of ART medication non-adherence, 2.52 (95% CI: 1.20, 5.28), after adjusting for gender. Conclusion: As previously found in the general population, we found significant associations between depression and smoking and other non-injection drug use among HIV-positive adults. Major depression was also associated with a greater odds of ART medication non-adherence, which is also consistent with the literature. Because HIV-positive adults have ongoing encounters with healthcare providers, screening and treatment for depression and other co-morbid substance use is needed to reduce an additional health burden in this population.

While cigarette smoking is a common-knowledge way to stay lean, it has long been known as a risk factor for diabetes and obesity. Here we establish that smoking causes fat gain and metabolic disruption in mice, effects which are exacerbated by a high-fat, high-sugar diet. We found that smoke exposure increases levels of ceramide—the lipid responsible for diet-induced insulin resistance—and that blocking ceramide production with the pharmacological inhibitor myriocin restored insulin sensitivity, stopped weight gain, and rescued mitochondrial respiration in vivo and in vitro.We also sought to assess the impact of the RAGE ligand HMGB1 on skeletal muscle metabolism. We found that respiration between vehicle and HMGB1-injected red gastrocnemius was comparable. In myotubes, adding myriocin treatment to the HMGB1 cells increased respiration above HMGB1 treatment alone. HMGB1 increased oxidative stress in cultured myotubes and increased the transcript levels of Spt2, the enzyme responsible for the rate-limiting step in ceramide synthesis, although transcript levels of markers of mitochondrial fission and fusion leave us unsure of HMGB1's impact on mitochondrial dynamics. HMGB1, even at an exceptionally low dose over only 2 weeks, did cause significant impairment in glucose and insulin tolerance tests. Considering HMGB1's accessibility as a therapeutic target, its involvement in metabolic disruption is worth pursuing further.

Cigarette smoking and depressive symptoms are two problems that affect adolescents’ health. Although it has been well-documented that a relationship exists between these two concerns, most researchers have used self-report methods to study smoking behaviors. While adolescents are typically accurate when reporting depressive symptoms, they tend to be less accurate reporting smoking. Moreover, research supporting the Prototype Willingness Model (PWM) has shown that the social cognitions of willingness to smoke, and the prototypes or images of smokers are predictors of smoking in adolescents. Little is known about the association between social cognitions and depressive symptoms in adolescence. In this study, I examined the relationship between cigarette smoking and depressive symptoms in high school students using a biological measure of cigarette smoking. First, I investigated whether depressive symptoms and cigarette smoking were related in a sample of 440 high school sophomore students from Iowa. Then, using data from 264 of the same participants, I examined whether smoking during or before the sophomore year of high school predicted depressive symptoms a year later when participants were in their junior year of high school. Conversely, I also examined whether depressive symptoms during the sophomore year of high school predicted cigarette smoking in the junior year of high school. Finally, I studied the relationship between social cognitions (i.e., prototypes and willingness) and depressive symptoms. An additional section explored whether the social cognitions predicted cigarette smoking. The findings did not provide evidence supporting a relationship between cigarette smoking and depressive symptoms when smoking was measured by a biological measure. Only self-report of smoking cigarettes significantly predicted depressive symptoms during the sophomore year of high school. Cigarette smoking during or before the sophomore year of high school did not predict depressive symptoms a year later. Similarly, depressive symptoms reported in the sophomore year of high school did not predict cigarette smoking a year later. For the social cognitions, willingness to engage in smoking behaviors and the prototypes or images adolescents have about teenagers who smoke were significantly associated with depressive symptoms. Only willingness to engage in smoking behaviors was a significant predictor of cigarette smoking. These results support the idea that the relationship between depressive symptoms and cigarette smoking varies when using different methodologies to assess smoking status. Also, the finding that social cognitions correlates with depressive symptoms could motivate further investigation. This work can also alert adults about other ways in which elevated depressive symptoms in adolescents may influence their perceptions.

In the present study, three self-managed treatment programs were compared with respect to their ability to effect and maintain change in the cigarette smoking behavior of 27 subject volunteers from the population of employees of a Veterans Administration hospital. Subjects were randomly assigned to a self—imposed delay group, a self-directed relaxation group, and a self-monitoring group. The experimental program lasted 6 weeks with a 20-minute individual meeting each week. Three months following treatment, subjects were contacted by mail and were asked to monitor their smoking behavior for one week, and to return their average daily smoking rate by mail. The results provide support for the effectiveness of the self-management technique of self-imposed delay as a durability—enhancing treatment procedure. The effectiveness of self-management techniques as a general class of treatment strategies was not supported. A task for future research would be to establish the effectiveness of the delay technique implemented earlier in the cigarette smoking chain, as well as to determine whether effectiveness is increased or decreased by a specification of the content of a delay interval.

Made available in DSpace on 2014-06-11T19:22:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-02Bitstream added on 2014-06-13T19:08:20Z : No. of bitstreams: 1 gomes_prl_me_prud.pdf: 496954 bytes, checksum: 1a8cc366f4f6c4e8b007f0dafc207ad0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / A gravidez é um período de ajustes metabólicos e, quando associado ao tabagismo provoca alterações que trazem malefícios tanto à saúde materna quanto à saúde fetal. Assim, o estudo investigou o efeito da exposição à fumaça de cigarro sobre a expressão do transportador de glicose GLUT4 e parâmetros séricos e morfométricos de ratas prenhes e sua prole. Foram utilizadas ratas Wistar divididas em: CG- controle sacrificadas após a gestação, com prole adotada pelo grupo CL; CL - controle sacrificadas após o término da lactação; FG – expostas à fumaça de cigarro até o período gestacional e sacrificadas posteriormente, com prole adotada pelo grupo FL; FG – expostas à fumaça de cigarro até o fim da amamentação e posteriormente sacrificadas. As proles foram divididas por sexo e de acordo com a exposição ou não da rata à fumaça. Foram coletados sangue e tecidos para análise de glicemia e do conteúdo gênico e protéico de GLUT4. Nas ratas expostas à fumaça de cigarro, houve redução de peso corpóreo e de tecido adiposo, aumento da glicemia e modulação do transportador GLUT4 no músculo esquelético. Nas proles, houve... / Pregnancy is a period of metabolic adjustments, and when associated with cigarette smoke causes changes both to maternal health as the fetal. The study has investigated the effect of cigarette smoke exposure on the expression of glucose transporter GLUT4 and morphometric parameters and serum of pregnant smoker rats and their offspring. Wistar rats were divided in: CG- nonsmokers sacrificed after pregnancy with offspring adopted by CL; CL – nonsmoker group sacrificed after the end of lactation; FG – smoker group sacrificed after pregnancy with offspring adopted by FL; FL – smoker sacrificed after the end of lactation. The offspring was divided by sex and according to the protocol of their mothers. Blood and tissue were collected for analysis of glucose and the content of GLUT4 gene and protein. In smoker mothers, body weight and adipose tissue were reduced, glucose level was increased, and GLUT4 expression was higher in skeletal muscle. In offspring... (Complete abstract click electronic access below)

Smoking remains the single most preventable cause of death worldwide and primary cause of several types of cancer, cardiovascular disease, and respiratory illness (USDHHS, 2014). Although the prevalence of smoking among the general population continues to decline, the prevalence of smoking among the veteran population remains high. In addition, the prevalence of smoking among veterans with substance and alcohol use disorders is 2 to 3 times higher than in the general population. Over the years, the VA has implemented empirically-based treatments for smoking cessation to address the cigarette smoking epidemic. These services, however, are greatly underutilized. Motivational interviewing (MI) has traditionally been used to treat alcohol dependence; however, its efficacy for smoking cessation has been mixed. There is some evidence, however, suggesting that MI could be used to motivate smokers to seek treatment. The purpose of this study was to use a brief MI intervention to motivate veteran smokers undergoing treatment for substance use to seek smoking cessation services at the VA. We recruited 60 veterans undergoing substance and alcohol use treatment at the Substance Use Disorders/Intensive Outpatient Program (SUDs/IOP) at the James A. Haley VA. Participants were randomized to one of two groups: MI vs. active control. We hypothesized that veterans in the MI condition would be more likely to seek services for smoking cessation compared to those in the control condition. Our findings supported our hypothesis: 40% of participants in the MI condition sought treatment to quit smoking after the intervention compared to 23% of participants in the control condition (p = .03, controlling for baseline differences in cessation motivation). In addition, we found that the MI intervention was most beneficial for individuals with lower baseline motivation to quit smoking. Although we did not find significant mediators of the effect of the intervention on our primary outcome, this study showed that a brief MI intervention can promote seeking of smoking cessation resources.

Fecundity, defined as the biologic capacity for reproduction, is measured operationally as time-to-pregnancy (TTP) among non-contracepting couples. While most couples conceive naturally within six menstrual cycles of trying, 10-24% of couples take longer than six cycles. Fecundity impairments are associated with long-term adverse health consequences including insulin resistance and gynecologic cancers, can cause substantial psychological and economic hardship, and cost over $5 billion annually in the U.S. Therefore, identifying risk factors for subfecundity in order to increase the chances of natural conception among pregnancy planners is an important public health goal. Environmental and psychosocial risk factors are understudied in relation to reproductive health. The goal of this dissertation is to examine the independent associations between exposure to tetrachloroethylene, perceived stress, and cigarette smoking and fecundability, the per cycle probability of conception. In study one, we used data from a retrospective cohort study of Cape Cod women who were exposed to tetrachloroethylene-contaminated drinking water in the 1960s-1980s to examine the relation between tetrachloroethylene exposure and fertility. We found that women with the highest modeled tetrachloroethylene exposure around the time of the pregnancy attempt had increased risk of TTP>12 months compared with unexposed women. Cumulative exposure, however, was not associated with elevated risk of TTP>12 months. Studies two and three used data from Pregnancy Study Online (PRESTO), a preconception cohort study of pregnancy planners from North America. In study two, we found that perceived stress levels in women, but not their male partners, were associated with lower fecundability, with little evidence of mediation by measured behavioral factors. In study three, we found that male current active smoking was associated with lower fecundability. In women, current smoking was only associated with reduced fecundability among women who smoked with high intensity and/or long duration. Passive smoking was not substantially associated with fecundability in either partner, but women exposed in utero to high intensity smoking had lower fecundability than unexposed women. Overall, we observed weak associations between tetrachloroethylene exposure, perceived stress, and active smoking and fertility among pregnancy planners. These findings indicate that environmental and psychosocial factors may play a role in the etiology of infertility. In addition, given that these exposures are common and modifiable, they may be important targets for public health interventions.