Publications

OBJECTIVE

To explore viral marketing strategies for Eclipse cigarettes used by the RJ Reynolds Company (Winston-Salem, North Carolina, USA).

METHODS

Analysis of previously secret tobacco industry documents and multimedia materials.

RESULTS

The failure of RJ Reynolds' (RJR) 1988 "smokeless" cigarette, Premier, was in part due to widespread bad word of mouth about the product's flavour, quality and difficulty of use. In 1994 RJR introduced an updated version of Premier, the ostensibly "reduced risk" Eclipse cigarette. RJR developed viral marketing channels to promote Eclipse using (1) exploratory interviews to motivate consumers to spread the word about Eclipse prior to market release, (2) promotional videos featuring positive feedback from test group participants to portray majority consensus among triers, (3) "Tupperware"-like parties for Eclipse where participants received samples to pass around in their social circles and (4) the Eclipse website's bulletin board as a forum for potential users to discuss the brand in their own words. These strategies targeted the brand's likeliest adopters, recruited informal and credible representatives of the product unaffiliated with RJR, and controlled the information spread about the product.

CONCLUSIONS

Viral marketing techniques may be particularly useful to promote new tobacco products such as Eclipse that have limited appeal and need a highly motivated audience of early adopters and acceptors. Such techniques help evade the mass rejection that could follow mass promotion, circumvent marketing restrictions, and allow tobacco companies to benefit from health claims made by consumers. Cigarette manufacturers must be held accountable for perceived health benefits encouraged by all promotional activities including viral marketing.

BACKGROUND

Wealthy women have higher rates of screening mammography than poor women do. Screening mammography is beneficial for women with substantial life expectancies, but women with limited life expectancies are unlikely to benefit. It is unknown whether higher screening rates in wealthy women are due to increased screening in women with substantial life expectancies, limited life expectancies, or both. This study examines the relationship between wealth and screening mammography use in older women according to life expectancy.

METHODS

A cohort study was performed of 4222 women 65 years or older with Medicare participating in the 2002 and 2004 Health and Retirement Survey. Women were categorized according to wealth and life expectancy (based on 5-year prognosis from a validated prognostic index). The outcome was self-reported receipt of screening mammography within 2 years.

RESULTS

Overall, within 2 years, 68% of women (2871 of 4222) received a screening mammogram. Screening was associated with wealth (net worth, > $100 000) and good prognosis (< or = 10% probability of dying in 5 years). Screening mammography was more common among wealthy women than among poor women (net worth, < $10 000) both for women with good prognosis (82% vs 68%; P < .001) and for women with limited prognoses (> or = 50% probability of dying in 5 years) (48% vs 32%; P = .02). These associations remained after multivariate analysis accounting for age, race, education, proxy report, and rural residence.

CONCLUSIONS

Poorer older women with favorable prognoses are at risk of not receiving screening mammography when they are likely to benefit. Wealthier older women with limited prognoses are often screened when they are unlikely to benefit.

BACKGROUNDS & AIMS

ATP8B1 is a phosphatidylserine flippase in the canalicular membrane; patients with mutations in ATP8B1 develop severe chronic (PFIC1) or periodic (BRIC1) cholestatic liver disease. We have observed that Atp8b1 deficiency leads to enhanced biliary cholesterol excretion. It has been established that biliary cholesterol excretion depends on transport by the heterodimer Abcg5/Abcg8. We hypothesized that the increased cholesterol output was due to enhanced extraction from the altered canalicular membrane rather than to higher Abcg5/Abcg8 activity. We therefore studied the relation between Abcg5/Abcg8 expression and biliary cholesterol excretion in mice lacking Atp8b1, Abcg8, or both (GF mice).

METHODS

Bile formation was studied in LXR agonist-fed wild-type mice as well as mice lacking Atp8b1 or Abcg8, or in GF mice upon infusion of taurocholate. Bile samples were analyzed for cholesterol, bile salt, phospholipids, and ectoenzyme content.

RESULTS

LXR agonist increased Abcg5/8 expression, and this was accompanied by increased biliary cholesterol output in both wild-type and Atp8b1(G308V/G308V) mice. However, Atp8b1(G308V/G308V) mice maintained higher cholesterol output. Although in Abcg8(-/-) mice biliary cholesterol output was severely reduced, GF mice displayed high biliary cholesterol output, which was comparable with wild-type mice. Bile of both Atp8b1(G308V/G308V) and GF mice displayed elevated levels of phosphatidylserine and sphingomyelin, indicating membrane stress.

CONCLUSIONS

Our data demonstrate that the increased biliary cholesterol excretion in Atp8b1-deficient mice is independent of Abcg5/8 activity. This implicates that Atp8b1 deficiency leads to a decrease in the detergent resistance and subsequent nonspecific extraction of cholesterol from the canalicular membrane by bile salts.

OBJECTIVE

To assess the utility of a panviral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections (RTIs).

STUDY DESIGN

The Virochip was compared with conventional direct fluorescent antibody (DFA)- and polymerase chain reaction (PCR)-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children.

RESULTS

The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity, 85% to 90%; specificity, >/=99%; positive predictive value, 94% to 96%; negative predictive value, 97% to 98%) in the detection of respiratory syncytial virus, influenza A, and rhinoviruses/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect.

CONCLUSIONS

Given its favorable sensitivity and specificity profile and expanded spectrum for detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric RTIs.

Cell fate decisions of pluripotent embryonic stem (ES) cells are dictated by activation and repression of lineage-specific genes. Numerous signaling and transcriptional networks progressively narrow and specify the potential of ES cells. Whether specific microRNAs help refine and limit gene expression and, thereby, could be used to manipulate ES cell differentiation has largely been unexplored. Here, we show that two serum response factor (SRF)-dependent muscle-specific microRNAs, miR-1 and miR-133, promote mesoderm formation from ES cells but have opposing functions during further differentiation into cardiac muscle progenitors. Furthermore, miR-1 and miR-133 were potent repressors of nonmuscle gene expression and cell fate during mouse and human ES cell differentiation. miR-1's effects were in part mediated by translational repression of the Notch ligand Delta-like 1 (Dll-1). Our findings indicate that muscle-specific miRNAs reinforce the silencing of nonmuscle genes during cell lineage commitment and suggest that miRNAs may have general utility in regulating cell-fate decisions from pluripotent ES cells.

CONTEXT

Colorectal cancer is the second leading cause of cancer death in the United States. Prevention has focused on the detection and removal of polypoid neoplasms. Data are limited on the significance of nonpolypoid colorectal neoplasms (NP-CRNs).

OBJECTIVES

To determine the prevalence of NP-CRNs in a veterans hospital population and to characterize their association with colorectal cancer.

DESIGN, SETTING, AND PATIENTS

Cross-sectional study at a veterans hospital in California with 1819 patients undergoing elective colonoscopy from July 2003 to June 2004.

MAIN OUTCOME MEASURES

Endoscopic appearance, location, size, histology, and depth of invasion of neoplasms.

RESULTS

The overall prevalence of NP-CRNs was 9.35% (95% confidence interval [95% CI], 8.05%-10.78%; n = 170). The prevalence of NP-CRNs in the subpopulations for screening, surveillance, and symptoms was 5.84% (95% CI, 4.13%-8.00%; n = 36), 15.44% (95% CI, 12.76%-18.44%; n = 101), and 6.01% (95% CI, 4.17%-8.34%; n = 33), respectively. The overall prevalence of NP-CRNs with in situ or submucosal invasive carcinoma was 0.82% (95% CI, 0.46%-1.36%; n = 15); in the screening population, the prevalence was 0.32% (95% CI, 0.04%-1.17%; n = 2). Overall, NP-CRNs were more likely to contain carcinoma (odds ratio, 9.78; 95% CI, 3.93-24.4) than polypoid lesions, irrespective of the size. The positive size-adjusted association of NP-CRNs with in situ or submucosal invasive carcinoma was also observed in subpopulations for screening (odds ratio, 2.01; 95% CI, 0.27-15.3) and surveillance (odds ratio, 63.7; 95% CI, 9.41-431). The depressed type had the highest risk (33%). Nonpolypoid colorectal neoplasms containing carcinoma were smaller in diameter as compared with the polypoid ones (mean [SD] diameter, 15.9 [10.2] mm vs 19.2 [9.6] mm, respectively). The procedure times did not change appreciably as compared with historical controls.

CONCLUSION

In this group of veteran patients, NP-CRNs were relatively common lesions diagnosed during routine colonoscopy and had a greater association with carcinoma compared with polypoid neoplasms, irrespective of size.

BACKGROUND

Tryptases are serine peptidases stored in mast cell granules. Rodents express 2 soluble tryptases, mast cell proteases (MCPs) 6 and 7. Human alpha- and beta-tryptases are orthologs of MCP-6. However, much of the ancestral MCP-7 ortholog was replaced by parts of other tryptases, creating chimeric delta-tryptase. Human delta-tryptase's limited activity is hypothesized to be due to truncation and processing mutations.

OBJECTIVE

We sought to probe the origins and consequences of mutations in primate delta-tryptases.

METHODS

Prosimian (lemur), monkey (macaque), great ape (orangutan, gorilla, and chimpanzee), and human delta-tryptase genes were identified by means of data mining and genomic sequencing. Resulting genes were analyzed phylogenetically and structurally.

RESULTS

The seminal conversion event generating the delta-tryptase chimera occurred early because all primates studied contain delta-tryptase genes. Truncation, resulting from a nonsense mutation of Trp206, occurred much later, after orangutans and other great apes last shared an ancestor. The Arg-3Gln propeptide mutation occurred most recently, being present in humans and chimpanzees but not in other primates. Surprisingly, the major active tryptase in monkeys is full-length delta-tryptase, not beta-tryptase, which is the main active tryptase in human subjects. Models of macaque delta-tryptase reveal that the segment truncated in human subjects contains antiparallel beta-strands coursing through the substrate-binding cleft, accounting for truncation's drastic effect on activity.

CONCLUSIONS

Transformations in the ancestral MCP-7-like gene during primate evolution caused dramatic variations in function. Although delta-tryptases are nearly inactive in humans, they are active and dominant in monkeys.