Ambient Air Pollution and Lung Cancer Risk in the Women's Health Initiative Observational Study

Thesis (Master's)--University of Washington, 2016-06

Multifaceted roles of the lysosome in the establishment and expansion of tuberculous infection

Thesis (Ph.D.)--University of Washington, 2016-04

Validation of self-reported cigarette smoking in a remote Australian Aboriginal community

Objective: To examine the relationship between self-reported tobacco smoking and urinary cotinine concentrations in the setting of a remote Aboriginal community. Methods: In a remote Northern Territory (NT) Aboriginal community the relationship between self-reported tobacco smoking and urinary cotinine concentrations was examined as part of a cross-sectional survey of cardiovascular risk factors. Current tobacco smoking was assessed as part of a questionnaire. The concentration of cotinine and cotinine/creatinine ratio (CCR) in a spot urine sample were used as a biochemical marker of nicotine exposure. Results: A total of 237 people took part in the survey, although completed questionnaires and urine results were available for 184 people. Current tobacco smoking was reported by 161 (69 [95% Cl 63 to 75]%) people, with higher rates among males (84/104, 81 [95% Cl 72 to 88]%) than females (77/129, 60 [95% Cl 51 to 68]%, p

Seed viability and dormancy mechanisms of Leucopogon melaleucoides Cunn. ex DC. (Epacridaceae)

Leucopogon melaleucoides, a flowering shrub, is desired by floricultural markets but is difficult to propagate. Seed viability was tested and dormancy mechanisms were studied to develop a commercial propagation system. Although around 56% of seed were viable, germination was completely inhibited unless the endocarp was removed. After-ripened seed (8 months after collection) germinated faster than fresh seed (2 days after collection), but germination occurred over a prolonged period (155 days). Germination of after-ripened seed was promoted with GA(3) or a commercial smoke product containing unknown plant growth regulators. All viable seed treated with GA(3) at 1000 mg L-1 had germinated after 24 days. The results suggest that both a physical and physiological dormancy mechanism occur for this species, with removal of the endocarp and pretreatment with 1000 mg L-1 GA(3) promoting complete germination of viable seed.

Defining nicotine dependence for genetic research: evidence from Australian twins

Background. Whether current criteria used to define nicotine dependence are informative for genetic research is an important empirical question. The authors used items of the DSM-IV and of the Heaviness of Smoking Index to characterize the nicotine dependence phenotype and to identify salient symptoms in a genetically informative community sample of Australian young adult female and mate twins. Method. Phenotypic and genetic factor analyses were performed on nine dependence symptoms (the seven DSM-IV substance dependence criteria and the two Heaviness of Smoking Index (HSI) items derived from the Fagerstrom Tolerance Questionnaire, time to first cigarette in the morning and number of cigarettes smoked per day). Phenotypic and genetic analyses were restricted to ever smokers. Results. Phenotypic nicotine dependence symptom covariation was best captured by two factors with a similar pattern of factor loadings for women and men. In genetic factor analysis item covariation was best captured by two genetic but one shared environmental factor for both women and men; however, item factor loadings differed by gender. All nicotine dependence symptoms were substantially heritable, except for the DSM-IV criterion of 'giving up or reducing important activities in order to smoke', which was weakly familial. Conclusions. The salient behavioral indices of nicotine dependence are similar for women and men. DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men.

Fruit processing, seed viability and dormancy mechanisms of Persoonia sericea A. Cunn. ex R. Br. and P-virgata R. Br. (Proteaceae)

The morphology of the fruit and difficulties with fruit processing impose major limitations to germination of Persoonia sericea and P. virgata. The mesocarp must be removed without harming the embryo. Fermentation of fruit or manual removal of the mesocarp was effective but digestion in 32% hydrochloric acid (HCl) completely inhibited germination. The endocarp is extremely hard and therefore very difficult and time consuming to remove without damaging the seeds. The most efficient method was cracking the endocarp with pliers, followed by manual removal of seeds. Germination was completely inhibited unless at least half of the endocarp was removed. Microbial contamination of the fruit and seeds was controlled by disinfestation and germination of the seed under aseptic conditions. The results suggest that dormancy in these species is primarily due to physical restriction of the embryo by the hard endocarp.

Improved germination of the Australian natives: Hibbertia commutata, Hibbertia amplexicaulis (Dilleniaceae), Chameascilla corymbosa (Liliaceae) and Leucopogon nutans (Epacridaceae)

Hibbertia commutata (Steudel), H. amplexicaulis (Steudel), Chameascilla corymbosa [(R.Br.) F.Muell. Ex Benth.] and Leucopogon nutans (E. Pritzel) are four Australian species that are difficult to germinate during mine-site rehabilitation. Laboratory germination trails were conducted to identify dormancy mechanisms and to improve germination response. Treatments applied to all species included scarification and scarification followed by soaking seeds in smoke water (1, 5 or 10%) or gibberellic-acid solution (50, 200 or 1000 muM). Additional treatments with kinetin solution (50, 200 or 1000 muM) and smoke water (50 or 100%) were applied to scarified or unscarified seeds of C. corymbosa. Thermal-shock treatment was applied to L. nutans fruit, some of which were subsequently scarified and subjected to both smoke water (10%) and gibberellic-acid solution (1000 muM). Significant germination increases were obtained by using dormancy-breaking treatments on H. commutata ( from 12.8 to 76.0%), H. amplexicaulis (from 6.8 to 55.1%) and C. corymbosa (from 48.5 to 86.4%). Scarification alone increased germination of both Hibbertia species, suggesting that these species display a physical seed coat-imposed dormancy mechanism. Germination of H. amplexicaulis was further increased by the application of gibberellic-acid solution, indicating a possible embryo-imposed dormancy mechanism. Scarification followed by the application of smoke water produced the highest germination response for C. corymbosa seeds. Scarification alone did not significantly increase germination, inferring the existence of a smoke-responsive embryo dormancy mechanism. Seeds of L. nutans, although viable, failed to germinate and are thought to display complex seed coat- and embryo-imposed dormancy mechanisms.

Changes in smoking behaviour among young women over life stage transitions

Objective: To examine changes in smoking behaviour among young women over four life stages: leaving home; employment or attending college or university; marriage; and parenthood. Methods: Young women participating in the Australian Longitudinal Study on Women's Health completed postal questionnaires in 1996 and 2000. Results: Unmarried women who moved out of their parents' home between 1996 and 2000 had higher odds of adopting smoking than those who had not lived with their parents at either time (OR 1.8, 95% Cl 1.2-2.6). Married women had lower odds of resuming smoking after quitting (OR 0.4, 95% Cl 0.2-0.7) than unmarried women. Women who were pregnant in 2000 had higher odds of quitting smoking (OR 3.8, 95% Cl 2.5-5.6) and women who were pregnant in 1996 and not in 2000 had higher odds of starting to smoke again (OR 3.2, 95% Cl 1.6-6.2) than women who were not pregnant. The odds of being a current smoker or adopting smoking were significantly greater for women who binge drank alcohol or used cannabis and other illicit drugs. Conclusions: Adoption, maintenance and cessation of smoking among young women is strongly related to major life stage transitions, illicit drug use and alcohol consumption. Implications: Life changes such as marriage and actual or contemplated pregnancy provide opportunities for targeted interventions to help women quit smoking and not relapse after having a baby. Legislation to control smoking on licensed premises would reduce the social pressure on women to smoke.

Effects of cigarette smoking and exposure to cadmium and lead on phenotypic variability of hepatic CYP2A6 and renal function biomarkers in men

Effects of cigarette smoking and exposure to dietary cadmium (Cd) and lead (Pb) on urinary biomarkers of renal function and phenotypic variability of cytochrome P450 2A6 (CYP2A6) were investigated in a group of 96 healthy Thai men with mean age of 36.7 year (19-57 years). In non-smokers, Cd burden increased with age (r = 0.47, P < 0.001). In current smokers, Cd burden increased with both age (r = 0.45, P = 0.01) and number of cigarettes smoked per day (r = 0.32, P = 0.05). Cd-linked renal tubular dysfunction was seen in both smokers and non-smokers, but Pb-linked glomerular dysfunction was seen in smokers only, possibly due to more recent exposure to high levels of Cd and Pb, as reflected by 30-50% higher serum Cd and Pb levels in smokers than non-smokers (P < 0.05). Exposure to dietary Cd and Pb appeared to be associated with mild tubular dysfunction whereas dietary exposure plus cigarette smoking was associated with tubular plus glomerular dysfunction. Hepatic CYP2A6 activity in non-smokers showed a positive association with Cd burden (adjusted P = 0.38, P = 0.006), but it showed an inverse correlation with Pb (adjusted beta = -0.29, P = 0.003), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. In contrast, CYP2A6 activity in current smokers did not correlate with Cd or Pb, but it showed a positive correlation with serum ferritin levels (r = 0.45, P = 0.01). These finding suggest that Pb concentrations in the liver probably were too low to inhibit hepatic synthesis of heme and CYP2A6 and that the concurrent induction of hepatic CYP2A6 and ferritin was probably due to cigarette smoke constituents other than the Cd and Pb. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Smoking and parenting among males in low socio-economic occupations

The role of fatherhood in family life has been accentuated as a consequence of societal change. This change, combined with knowledge about the harmful consequences of passive smoking, has focused attention on males who smoke and are the partners of pregnant women. Of particular interest are low socio-economic groups because of their higher smoking rates. This study examines smoking and parenting in a sample of 561 males in semi-skilled and unskilled occupations (with pregnant partners) who were recruited into a self-help smoking cessation programme. Parenting related variables predicted smoking cessation, particularly knowledge about passive smoking. A high level of knowledge about the effects of passive smoking on a baby was associated with one or more quit attempts early in the partner's pregnancy and smoking cessation. Confidence to quit during the pregnancy was also associated with smoking cessation. These results could be incorporated into smoking cessation and antenatal programmes to improve the health of families.

Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies

Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a vital poison for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N-G-methyl-L-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-today care resuscitative measures.

Risk of non-small cell lung cancer and the cytochrome P4501A1 Ile462Val polymorphism

Objective: The Ile462Val substitution in the cytochrome P450 1A1 gene (CYP1A1) results in increased enzymatic activity. Preliminary data suggesting a link between this polymorphism and lung cancer risk in Caucasians are inconsistent, reflecting small sample sizes and the relatively low frequency of the variant. Methods: The data set consisted of 1050 primary non-small cell lung cancer cases and 581 controls, a large homogenous population designed specifically to address previous inconsistencies. Patients were genotyped using a PCR-RFLP technique. Results: Carriers of the valine allele, CYP1A1*2C, (Ile/Val or Val/Val genotypes) were significantly over-represented in non-small cell lung cancer compared to controls (OR=1.9; 95% CI=1.2-2.9; p=0.005) when adjusted for confounders, particularly in women (OR=4.6; 95% CI=1.7-12.4; p=0.003). The valine variant was statistically significantly over-represented in cases of lung cancer younger than the median age (64 years) (OR=2.5; 95% CI=1.3-4.8; p=0.005) and cases with less than the median cumulative tobacco-smoke exposure (46 pack-years) (OR=2.4; 95% CI=1.3-4.7; p=0.007). Conclusions: These new data establish an association between the CYP1A1 Ile462Val polymorphism and the risk of developing non-small cell lung cancer, especially among women.

Characteristics of older dietary supplement users: Review of the literature

Published literature reports rates of dietary supplement usage by individuals aged 60 years or more to be 16−60%. Prevalence figures are dependent on the population studied and the method of data collection. In general, older supplement users are female, Caucasian and well educated, with healthier lifestyle practices than non-supplement users, and they are less likely to be overweight or to smoke. Neither income nor self-rated health status are reliable predictors of supplement use in this group. In many cases older supplement users report higher intakes of several micronutrients from food than older non-supplement users. Current patterns of supplement use by the older person reveal that although they consume a range of products, they do not supplement with nutrients that are of particular benefit to them. The supplements most commonly consumed by individuals aged 60 years and over are multivitamins and minerals, vitamin C and vitamin E preparations. There is insufficient data to quantify the dosage, frequency and duration of supplement use by the older population. Obtaining this information and data about herbal medicine use is an important step towards minimising the risk of drug–nutrient–herbal interactions. Identifying the health professionals who monitor the appropriateness and safety of supplement use in older individuals, particularly given the already high use of medication in this population, also needs to be a focus of future utilisation investigations. This systematic review of the literature published between 1982 and 2003 aims to measure the patterns of dietary supplement use by community-living individuals aged 60 years and over and to profile the characteristics of older supplement users.

Role of smoking in global and regional cardiovascular mortality

Background - Smoking is a major cause of cardiovascular disease mortality. There is little information on how it contributes to global and regional cause-specific mortality from cardiovascular diseases for which background risk varies because of other risks. Method and Results - We used data from the American Cancer Society's Cancer Prevention Study II (CPS II) and the World Health Organization Global Burden of Disease mortality database to estimate smoking-attributable deaths from ischemic heart disease, cerebrovascular disease, and a cluster of other cardiovascular diseases for 14 epidemiological subregions of the world by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.62 (95% CI, 1.27 to 2.04) million cardiovascular deaths in the world, 11% of total global cardiovascular deaths, were due to smoking. Of these, 1.17 million deaths were among men and 450 000 among women. There were 670 000 (95% CI, 440 000 to 920 000) smoking-attributable cardiovascular deaths in the developing world and 960 000 (95% CI, 770 000 to 1 200 000) in industrialized regions. Ischemic heart disease accounted for 54% of smoking-attributable cardiovascular mortality, followed by cerebrovascular disease (25%). There was variability across regions in the role of smoking as a cause of various cardiovascular diseases. Conclusions - More than 1 in every 10 cardiovascular deaths in the world in the year 2000 were attributable to smoking, demonstrating that it is an important preventable cause of cardiovascular mortality.