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Poster Presentation at the 11th International Conference on Toxicology. 2007. Lense M, Stroud LR, Niaura R, Shenassa E, Lipsitt L, Paster R, LeWinn K, Buka S. Markers of fetal nicotine exposure and neonatal neurobehavior: The National Collaborative Perinatal Project. Presented at the 14th Annual Society for Research on Nicotine and Tobacco Meeting. Portland, OR, Feb 27-Mar 1, 2008. Marcello D, Lense M, Salisbury A, Stroud LR. Links between fetal and infant response in smokingexposed and unexposed offspring: a pilot. Poster Presentation at the 38th Annual International Society for Research on Psychoneuroendocrinology Conference, 2007. Stroud LR, Paster RL, Papandonatos G, Niaura R, Salisbury AL, Battle C, Lagasse L, Lester B. Maternal smoking during pregnancy and newborn neurobehavior: effects at 10-27 days. J Pediatr 2009;154:10- 16. Svenson AE, Stroud LR, Lester B, Lagasse L, Salisbury A, Niaura R. Does breast-feeding moderate the influence of smoking during pregnancy on newborn behavior? Poster Presentation at the Annual Mental Health Sciences Research Day. Brown Medical School, 2008. SECOND-HAND TOBACCO SMOKE AND NEONATES AND PREDISPOSITION TO COPD AND DURABLE EFFECTS OF NEWBORN CIGARETTE SMOKE EXPOSURE ON THE ADULT LUNG Sharon A. McGrath-Morrow, MD; The Johns Hopkins University; CIA 2007 Exposure to cigarette smoke is the most frequently recognized risk factor for the development of COPD. Impaired alveolar growth during infancy may increase the risk of developing COPD in adulthood. The degree of altered lung structure in conjunction with oxidative stress, cell apoptosis, protease imbalance, inflammation, and altered immunity may determine the severity and onset of COPD. Early postnatal insults such as prematurity or lower respiratory tract infections may disrupt alveolar growth, thus increasing the likelihood of developing COPD when exposed to cigarette smoke later in life. The overall objective of the study is to understand the mechanisms that increase susceptibility of developing lung to cigarette smoke, leading to impaired lung function and increased likelihood of COPD in adulthood. Preliminary studies revealed that chronic cigarette smoke exposure led to increased oxidative stress, apoptosis, and increased transforming growth factor-beta signaling in newborn lungs of mice. At 8 weeks of age, mice exposed to neonatal cigarette smoke had a mild but significant increase in airspace size suggesting that cigarette smoke in the neonatal period can subsequently alter adult lung structure. Neonatal SHS can also polarize immature lung towards a more pronounced TH2 response. Significant down-regulation of many type 1 and type 2 interferon-response genes were found, suggesting a link between cigarette smoke exposure in infancy and inhibition of TH1 response gene expression. Taken together, these findings will help explain the association between cigarette smoke exposure in infancy and increased risk of COPD later in life. Exposure to SHS during early postnatal life may cause durable changes in the adult lung as well. To evaluate this, Dr. McGrath-Morrow and her collaborators exposed newborn C57/B6 mice to two weeks of CS in the newborn period and then assessed lung structure and function at six months of age. Gene expression profiling was also performed to determine if exposure to CS in early life could alter gene expression in the adult lung. The investigators showed that at six months, mice exposed to two weeks of CS in the newborn period had a modest but significant increase in total lung capacity (TLC) compared to controls (1.5ml +/- 0.1 versus 1.3 ml +/-0.1.) Active and passive cigarette smoking are risk factors among women of reproductive age, leading to reproductive health morbidity, including fetal and infant mortality, and developmental problems with the newborn. However, the underlying physiological mechanisms for these ill-effects are not fully understood. Some of the suspected mechanisms responsible for these adverse effects may involve hormonal disturbances and may be associated with both antithyroid and stimulating effects on the thyroid. The objective of Dr. McGrath-Morrow’s study was to quantitate and compare serum thyroid hormone and thyrotropin concentrations in active smokers, passive smokers and non-smokers, and determine associations with cigarette tobacco smoke exposure. Serum was obtained from women (18-44y). Thyroxine (T4), triiodothyronine (T3) and cotinine concentrations were quantified using isotope dilution high performance liquid chromatography tandem mass spectrometry (LC/MS/MS), and thyroidstimulating hormone (TSH) concentrations by chemiluminescence. The investigators found that median TSH concentrations were lower in active smokers compared to passive smokers and non-smokers (non-exposed.) Median serum T3 concentrations were consistently lower in active smokers than non-smokers. Pair-wise comparisons of the three study groups indicate statistically significant differences in mean T4 (Pvalue=0.0065) and T3 (Pvalue=0.0013). 2 0 0 P A G E
This study is unique in examining the association of serum cotinine and thyroid hormone concentrations using LC/MS/MS in women smokers, passive smokers and non-smokers. Active and passive exposure to cigarette tobacco smoke causes a mild stimulating effect on the thyroid as reflected in low normal serum TSH levels in this cohort of women. FAMRI Supported Publications McGrath-Morrow S, Rangasamy T, Cho C, Susson T, Neptune E, Wise R, Tuder RM, Biswal S. Impaired lung homeostasis in neonatal mice exposed to cigarette smoke. Am J Respir Cell Mol Biol 2008;38:393- 400. EFFECT OF SECOND HAND TOBACCO SMOKE ON FETAL BODY SIZE AND BRAIN SIZE Hamisu M. Salihu, MD; University of Medicine and Dentistry of New Jersey; YCSA 2003 The main purpose of this project is to estimate the association between prenatal tobacco smoke exposure and fetal and brain growth trajectories using ultrasound measurements. The results of the study will add substantially to current knowledge regarding the relationship between SHS exposure and fetal morbidity in utero. FAMRI Supported Publications Alexander GR, Wingate MS, Salihu H, Kirby RS. Fetal and neonatal mortality risks of multiple births. Obstet Gynecol Clin North Am 2005;32:1-16. Alexander MR, Salihu HM, Dwight RJ. Survival of triplets born to United States teenagers. Am J Obstet Gynecol 2004;191:2097-2102. Alio AP, Salihu HM. Maternal determinants of pediatric preventive care utilization among blacks and whites. J Natl Med Assoc 2005;97:792-797. Aliyu MH, Jolly PE, Ehiri J, Salihu HM. High parity and adverse birth outcomes. Exploring the maze. Birth 2005;32:45-59. Aliyu MH, Salihu HM, Keith LG, Ehiri JE, Islam MA, Jolly PE. Extreme parity and risk of stillbirth. Obstet Gynecol 2005;106:446-453. Aliyu MH, Salihu HM, Keith LG, Ehiri JE, Islam MA, Jolly PE. High parity and fetal morbidity outcomes. Obstet Gynecol 2005;105:1045-1051. Aliyu MH, Salihu HM, Keith LG, Ehiri JE, Islam MA, Jolly PE. Trends in birth across high parity groups by race/ethnicity and maternal age in the United States. J Natl Med Assoc 2005;97:799-804. Ananth CV, Smulian JC, Srinivas N, Getahun D, Salihu HM. Risk of infant mortality among twins in relation to placental abruption: contributions of preterm birth and restricted fetal growth. Twin Res Hum Genet 2005;8:524-531. Boulet S, Alexander GR, Salihu HM. Secular trends in c-section rates among macrosomic deliveries in the United States, 1989-2000. J Perinatol 2005;25:569-576. Chalo RN, Salihu HM, Nabukera S, Zirabamuzale C. Referral of high-risk pregnant mothers by trained TBAs in Buikwe county, Uganda. J Obstet Gynaecol 2005;25:554-557. Emusu D, Salihu HM, Aliyu ZY, Pierre-Louis BJ, Druschel CM, Kirby RS. Gastroschisis, low maternal age, and fetal morbidity outcomes. Birth Defects Res A Clin Mol Teratol 2005;73:649-654. Jaquet D, Shailender S, Alexander GR, Czernichow P, Collin D, Salihu HM, Kirby RS, Lavy-Marchal C. Significant paternal contribution to the risk of small-for-gestational age. Br J Obstet Gynaecol 2005;112:153-159. Kirby RS, Salihu HM. The contribution of birth weight and birth weight characteristics to developmental outcome. Am J Perinatol 2005;22:227-229. Kristensen S, Salihu HM, Keith LG, Kirby RS, Fowler KB, Pass MB. SGA subtypes and mortality risk among singleton births. Early Hum Dev 2007;83:99-105. Naik E, Karpur A, Taylor R, Ramaswami B, Ramachandra S, Balasubramaniam S, Galwankar S, Sinnott J, Nabukera S, Salihu HM. Rural Indian tribal communities: an emerging high-risk group for HIV/AIDS. BMC Int Health Hum Rights 2005;5:1. Salihu HM, Aliyu HM, Akintobi TH, Bosny JPL, Kirby RS, Alexander GR. The impact of advanced maternal age (> or = 40 years) on birth outcomes among triplets: a population study. Arch Gynecol Obstet 2005;271:132-137. Salihu HM, Aliyu MH, Kirby RS. Fetal growth of twins in nicotine-exposed uterine environment. Am J Perinatol 2005;22:421-427. Salihu HM, Aliyu MH, Sedjro JE, Oluwatade OJ, Alexander GR. Teen twin pregnancies and fetal growth P A G E 2 0 1
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MISSION FAMRI is an Independent Not
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FOREWORD David Sidransky, MD, Vice-
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FAMRI CENTERS OF EXCELLENCE........
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PAI-1 And Airway Remodeling In Seco
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Promoter Hypermethylation As A Mole
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Expression Profiling Of Blood In Lu
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Inhibition Of Hedgehog Signaling By
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Genetic Epidemiology Of Pulmonary F
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Reducing Second Hand Tobacco Smoke
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SINUSITIS .........................
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INTRODUCTION David M. Burns, MD, Pr
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FAMRI AWARD CATEGORIES The Board of
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HIGHLIGHTED FAMRI FUNDED RESEARCH C
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Xia L, Crane-Godreau M, Deng B, Lei
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Farassati F, Yang A-D, Lee P WK. On
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Nicotine & Tobacco Research 2007;9:
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homes where smoking is banned are m
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a survey-based COPD severity score.
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allergic rhinitis have increased re
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However, while the economic costs a
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mitochondrial adenosine diphosphate
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CHR, and CDE. The promoter architec
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Trends Mol Medicine 2007;13:150-157
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was also demonstrated to be effecti
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and are currently in clinical testi
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Academic Societies’ Meeting. Hono
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acceptability, and usefulness of us
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utilize telephone conference call f
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FAMRI-FUNDED RESEARCH COMBATING EFF
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act via limited proteolysis of subs
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was significantly higher in Nic:RSV
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presenting cells (APC) in vitro; an
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FAMRI Supported Publications Collac
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nisms of combostatin and its parent
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Bladder cancer progression involves
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45, NPV = 8%), 3 months (n = 42, NP
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THE EFFECT OF ADENYLATE KINASE 3 ON
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Agency report in 2006 (ftp://ftp.ar
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Narayan S, Jaiswal AS. Structure-ba
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in the duration of the cigarette sm
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ENVIRONMENTAL AND GENETIC RISK FACT
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Estrogen activates the cell cycle b
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Schaeffer MW, Sinha Roy S, Mukherje
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east tumors. When breast cancer cel
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is to identify and characterize key
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of these target genes are regulated
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CANCER, GASTRIC CURRENT RESEARCH GA
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CANCER, HEAD AND NECK CURRENT RESEA
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Tran HM, Shi G, Li G, Carney JP, O
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ANALYSIS OF SERUM PEPTIDES ASSOCIAT
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(BE), gastroesophageal reflux disea
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CANCER, HEAD AND NECK COMPLETED RES
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in normal epithelia, was shown to b
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Commentary: Bonn, D. Urine test for
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disease (COPD), innate immune dysfu
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SCLC. The foundation for this appro
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Witta SE, Gemmill RM, Hirsch FR, Co
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MYC-induced lymphomagenesis. It wil
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PUMA Mediates Intestinal Apoptosis
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leomycin-induced pulmonary fibrosis
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dimensional magnetic resonance micr
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vaccine, Ad.p53-DC, was well tolera
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esults of these studies should also
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prostaglandin E2 in non-small-cell
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were sequenced from NSCLC tissue an
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expression has a protective effect
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evaluate the expression level of Id
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as a target for the sensitization o
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Cancer Biol Ther 2006;5(1):48-53. A
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REGULATION OF TGF BETA SIGNALING IN
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among men exposed to cigarette smok
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FAMRI Supported Publications Gibbs
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or 500 ppm CO for 30 days. Blood pr
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adiponectin signals through activat
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CARDIOVASCULAR COMPLETED RESEARCH S
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EFFECTS OF SECOND HAND TOBACCO SMOK
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nicotine administration in vivo on
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degradation of type III collagen in
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wild-type (WT) mice and mice geneti
Page 162 and 163: REDUCED NEUTROPHIL DEATH IN TOBACCO
Page 164 and 165: H 2 O 2 -induced nuclear fragmentat
Page 166 and 167: The aims of this study are: 1) to d
Page 168 and 169: tion (GWA) studies of quantitative
Page 170 and 171: propagation of emphysema by alveola
Page 172 and 173: duced mainly by alveolar type-II ep
Page 174 and 175: concentrations of inflammatory indi
Page 176 and 177: subglottis. Arch Otolaryngol Head N
Page 178 and 179: detector row CT (MDCT), 2005. Prese
Page 180 and 181: of smoke-free homes: findings from
Page 182 and 183: Travers MJ, Hyland A. Wisconsin Air
Page 184 and 185: understood there would be several v
Page 186 and 187: Travers MJ, Cummings KM, Repace JL,
Page 188 and 189: REDUCING SHS: CARDIAC AND ASTHMA OU
Page 190 and 191: tobacco companies fought tobacco co
Page 192 and 193: consumer acceptance through Web-bas
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Page 196 and 197: youth to magazine tobacco advertisi
Page 198 and 199: Stukel JM, Heys JJ, Caplan MR. Opti
Page 200 and 201: EXPOSURE TO SECOND HAND TOBACCO SMO
Page 202 and 203: aldosterone, cortisol, corticostero
Page 204 and 205: the expression of numerous genes th
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Page 216 and 217: tobacco exposure (biologic measures
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Page 220 and 221: EPITHELIUM AND IMMUNOMODULATION IN
Page 222 and 223: patency was best assessed using hig
Page 224 and 225: significant increases in sinusitis
Page 226 and 227: VISION ONGOING RESEARCH GENE PROFIL
Page 228 and 229: FAMRI DISTINGUISHED PROFESSORS FAMR
Page 230 and 231: is a strong motivator for smoking c
Page 232 and 233: egulations and attitudes towards th
Page 234 and 235: y the tobacco industry of the harmf
Page 236 and 237: epair capacity assays. Her collabor
Page 238 and 239: Society for Research on Nicotine an
Page 240 and 241: PERSONAL THOUGHTS FROM THE FLIGHT A
Page 242 and 243: APPENDICES: LIST OF FAMRI GRANTEES
Page 244 and 245: BDA Butter, Karen A., MLS Universit
Page 246 and 247: AWARD INVESTIGATOR INSTITUTION TITL
Page 254 and 255: APPENDICES: ACRONYMS The following
Page 256 and 257: apoptosis. COPD. c2008;5:153-162. A
Page 258 and 259: KW, Lengauer C. Identification of c
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Measuring disease-specific quality
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Mukherjee M, Schuldenfrei A, Kowals
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sion attenuates cigarette smoke- or
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Kuck J, Bauer JA. Racial difference
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2008;26:856-862. Helfrich BA, Raben
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acute nephritis. Am J Nephrol 2008
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O’Malley BW. Double DNA repair hi
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of base excision repair pathways. C
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virotherapy of anaplastic thyroid c
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Marsit CJ, Posner MR, McClean MD, K
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2008. Mukhopadhyay S, Mukherjee S,
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Pache JC, Burton DW, Deftos LJ, Has
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2004;114:1248-1259. Rangasamy T, Gu
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Childhood pregnancy (10-14 years ol
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J Public Health 2004;94:1959-1964.
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2007;67(11):5337-5344. Sullivan AK,
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2005;90:5265-5269. Vassallo R, Kroe
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Fong Y. Effective treatment of head
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apoptosis control. Biochem Biophys
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APPENDICES: INDEX BY AUTHOR Abdulla
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Palmer, James N 235 Pan, Quintin 23
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NOTES: 2 9 2 P A G E
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ATTRIBUTION FLIGHT ATTENDANT MEDICA
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