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Biomedical subjects

David E Nelson

Publications and source records attributed to David E Nelson.

At least 19 recordsLinked to original sources
PubMed2007

Chlamydial interferon gamma immune evasion influences infection tropism.

Chlamydia trachomatis is a human pathogen and Chlamydia muridarum is a mouse pathogen but paradoxically, they share near genomic synteny. The majority of strain-variable genes are located primarily in a hyper-variable region termed the plasticity zone. Tryptophan synthase and cytotoxin are plasticity zone genes unique to the human and murine strains, respectively. Tryptophan synthase is a virulence factor that differentiates C. trachomatis strains into genital and ocular disease pathotypes, whereas cytotoxin(s) is a virulence factor linked to murine infection tropism. Divergence in these loci is strongly correlated with host-specific interferon gamma effector activities, suggesting that these virulence genes have co-evolved with their respective hosts as a primary mechanism to evade innate immunity. These findings have important implications for chlamydial animal modeling studies.

Animals↗
PubMed2006

Automated tracking of gene expression in individual cells and cell compartments.

Many intracellular signal transduction processes involve the reversible translocation from the cytoplasm to the nucleus of transcription factors. The advent of fluorescently tagged protein derivatives has revolutionized cell biology, such that it is now possible to follow the location of such protein molecules in individual cells in real time. However, the quantitative analysis of the location of such proteins in microscopic images is very time consuming. We describe CellTracker, a software tool designed for the automated measurement of the cellular location and intensity of fluorescently tagged proteins. CellTracker runs in the MS Windows environment, is freely available (at http://www.dbkgroup.org/celltracker/), and combines automated cell tracking methods with powerful image-processing algorithms that are optimized for these applications. When tested in an application involving the nuclear transcription factor NF-kappaB, CellTracker is competitive in accuracy with the manual human analysis of such images but is more than 20 times faster, even on a small task where human fatigue is not an issue. This will lead to substantial benefits for time-lapse-based high-content screening.

Animals↗
PubMed2006

A national surveillance system for tracking tobacco news stories.

BACKGROUND: Two of the major goals of tobacco prevention and control activities are to change social norms and influence policy. The news media can play an important role for achieving both goals. METHODS: The Centers for Disease Control and Prevention's Office on Smoking and Health created a surveillance system to track tobacco stories in the news media beginning in 2004. The system was developed based on reviewing lessons from previous news media tracking efforts, including defining the purpose of the system, using a parsimonious approach to sample media outlets, and attending to data-quality issues. Tobacco news stories were systematically identified and coded from ten newspapers, four news wire services, and seven national television networks. RESULTS: Findings indicated that from January 2004 through June 2005, tobacco-related stories were in selected major newspapers virtually every day. More than 70% of all newspaper stories contained one of only three main story themes: policy or regulation (31.0%), legal issues (23.8%), or health effects or statistics (18.1%). Television news stories on tobacco were much less common, but increased substantially during the first 6 months of 2005 compared to 2004. Health effects/statistics (50.5%) were the dominant theme for television, with policy/regulation a distant second (19.5%). CONCLUSIONS: Tobacco-related media coverage can be systematically tracked and characterized. These findings may have value to public health researchers and policymakers who wish to evaluate efforts to curb tobacco-related disease.

Mass Media↗
PubMed2006

Socioeconomic status and trends in disparities in 4 major risk factors for cardiovascular disease among US adults, 1971-2002.

BACKGROUND: It is unknown whether the previously recognized disparities in cardiovascular disease (CVD) risk factors related to annual income and educational level have diminished, persisted, or worsened in recent decades. The objective of this study was to examine 31-year trends in CVD risk factors by annual income and educational levels among US adults. METHODS: Four cross-sectional national surveys were used: National Health and Nutrition Examination Survey I (1971-1974), II (1976-1980), III (1988-1994), and 1999-2002. The main outcome measure was prevalence of high cholesterol (> or =240 mg/dL [> or =6.2 mmol/L]), high blood pressure (140/90 mm Hg), smoking, and diabetes mellitus. RESULTS: Between 1971 and 2002, the prevalence of all CVD risk factors, except diabetes, decreased in all income and education groups, but there has been little reduction in income- and education-related disparities in CVD risk factors and few improvements during the past 10 years. The prevalence of high blood pressure declined by about half in all income and education groups, ranging from 30.3% to 40.6% in 1971-1974 and 16.4% in 1999-2002, with the greatest reduction among those in the lowest income quartile and those with less than a high school education (18.0 and 15.9 percentage points, respectively). High cholesterol prevalence also declined in all groups and ranged from 28.8% to 32.4% in 1971-1974 and 15.3% to 22.0% in 1999-2002, with the largest decline (15.9 percentage points) among people with the highest incomes. Education- and income-related disparities in smoking widened considerably, because there were large declines in smoking prevalence among people with high incomes and education (from about 33% in 1971-1974 to about 14%-17% in 1999-2002) but only marginal reductions among those with low incomes and education (about 6-percentage point decline). Diabetes prevalence increased most among persons with low incomes and education. CONCLUSIONS: Despite the general success in reducing CVD risk factors in the US population, not all segments of society are benefiting equally and improvements may have slowed. Education- and income-related disparities have worsened for smoking, and increases in diabetes prevalence have occurred primarily among persons with a lower socioeconomic status. Diabetes prevention and smoking prevention and cessation programs need to specifically target persons of lower income and education.

Adult↗
PubMed2006

Trends in smokeless tobacco use among adults and adolescents in the United States.

OBJECTIVES: Smokeless tobacco has many adverse health effects. We analyzed long-term national trends in smokeless tobacco use. METHODS: We used 1987 to 2000 National Health Interview Survey data for adults aged 18 years and older, 1986 to 2003 data from Monitoring the Future surveys of adolescents, and 1991 to 2003 data from the Youth Risk Behavior Survey for 9th- to 12th-grade students to examine overall and demographic-specific trends. RESULTS: Smokeless tobacco use among adult and adolescent females was low and showed little change. Smokeless tobacco use among men declined slowly (relative decline=26%), with the largest declines among those aged 18 to 24 years or 65 years and older, Blacks, residents of the South, and persons in more rural areas. Overall and demographic-specific data for adolescent boys indicate that smokeless tobacco use increased for 12th-grade students from 1986 until the early 1990s, but has subsequently declined rapidly in all grades since then (range of relative overall declines=43% to 48%). CONCLUSIONS: Smokeless tobacco use has declined sharply, especially among adolescent boys. Ongoing prevention and cessation efforts are needed to continue this trend.

Adolescent↗
PubMed2006

Changes in newspaper coverage about hormone therapy with the release of new medical evidence.

BACKGROUND: Results of 2 trials of postmenopausal hormone therapy (HT) challenged established practice patterns; 1 was not associated with changes in HT use, whereas the other was associated with substantial decline. Differential coverage by lay newspapers may have contributed to the differential impact. OBJECTIVE: To examine newspaper coverage of HT before and after the publication of the Heart and Estrogen Replacement Study (HERS) in August 1998, and the main findings of the estrogen plus progestin therapy arm of the Women's Health Initiative (EPT-WHI) in July 2002. DESIGN: Longitudinal review of newspaper articles, 1998 to 2003 (n=663). SETTING: Twenty local and 6 regional/national newspapers. MEASUREMENTS: Number and content of articles about HT. RESULTS: The average number of articles about HT published during the month of the publication of the EPT-WHI was at least 8-fold greater than the number of articles published on the topic during any prior period. While the majority of articles in all periods presented information about the potential benefits of HT, information about harms became more common than information about benefits during the 2 months before the publication of the EPT-WHI, when the trial participants were notified of the early termination of the study. The presentation of specific health harms was more common after the publication of the EPT-WHI than after the publication of HERS. Few articles in any period used visual aids. CONCLUSIONS: The publication of the EPT-WHI was associated with a change in both the volume and content of newspaper coverage about HT.

Estrogen Replacement Therapy↗
PubMed2006

Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.

Apoptosis↗
PubMed2006

Reactions of young adult smokers to warning labels on cigarette packages.

BACKGROUND: In 1984, the United States Congress enacted legislation requiring four new warning labels for cigarettes; warning labels in the United States have not changed since then. Other countries, such as Canada, have taken a more active and aggressive approach. The purpose of this study was to examine how U.S. smokers and former smokers might respond to stronger and more graphic warnings for U.S. cigarettes packages. METHODS: Data were collected in 2003 and analyzed in 2004. The perceived impact and effectiveness of the more-explicit Canadian labels was examined among young adult smokers (n=572) and former smokers (n=191) between the ages of 18 and 24 years in the United States, using a web-based survey that allowed participants to view both the text-only and the text-plus-graphic warning labels. RESULTS: Both current and former smokers thought that cigarette warning labels with text plus graphics were substantially more of a deterrent than text-only labels. The perceived effectiveness of these labels was not only higher overall, but also for the specific areas of smoking-related health effects, prevention, cessation, and maintenance of abstinence. Few differences were noted by gender. CONCLUSIONS: The findings from this study support previous research that has found that text-plus-graphic warning labels are more salient and potentially more effective than text-only labels.

Adolescent↗
PubMed2006

Dissemination of physical activity evidence, programs, policies, and surveillance in the international public health arena.

The concepts of dissemination can be applied to the international challenges of promoting physical activity. With the 2004 release of the World Health Organization Global Strategy for Diet and Physical Activity, risk factor reduction and noncommunicable disease control are of global health interest. A six-step framework is proposed for understanding the attributes of successful international dissemination. These include the development of clear and evidence based resources or innovations, defining the target audience, selecting communication channels, engaging decision makers, and developing evaluation frameworks around dissemination. Four case studies to illustrate aspects of the framework are presented: (1) learning from dissemination of effective tobacco control initiatives, (2) the experience of developing global measures and surveillance systems for physical activity, (3) case study of disseminating the Agita program-an effective community wide intervention, and (4) disseminating the World Health Organization Global Strategy on Diet and Physical Activity. Substantial similarities across the experiences described in these case studies suggest underlying common themes for international dissemination, but developing a stronger evidence base for dissemination efforts remains a research priority.

Diffusion of Innovation↗
PubMed2006

Inhibition of chlamydiae by primary alcohols correlates with the strain-specific complement of plasticity zone phospholipase D genes.

Members of the genus Chlamydia are obligate intracellular pathogens that have a unique biphasic developmental cycle and interactions with host cells. Many genes that dictate host infection tropism and, putatively, pathogenic manifestations of disease are clustered in a hypervariable region of the genome termed the plasticity zone (PZ). Comparative genomics studies have determined that an uncharacterized family of PZ genes encoding orthologs of eukaryotic and prokaryotic members of the phospholipase D (PLD) enzyme family varies among chlamydiae. Here, we show that the PZ PLD (pzPLD) of Chlamydia trachomatis are transcribed during both normal and persistent infection and that the corresponding PLD proteins are predominantly localized in reticulate bodies on the inner leaflet of the inclusion membrane. Further, we show that strains of chlamydiae encoding the pzPLD, but not a strain lacking these genes, are inhibited by primary alcohols, potent PLD inhibitors, during growth in HeLa 229 cells. This inhibitory effect is amplified approximately 5,000-fold during recovery from persistent infection. These findings suggest that the chlamydial pzPLD may be important, strain-specific, pathogenesis factors in vivo.

Alcohols↗
PubMed2005

Chlamydial IFN-gamma immune evasion is linked to host infection tropism.

Chlamydiae are obligate intracellular pathogens that can exhibit a broad host range in infection tropism despite maintaining near genomic identity. Here, we have investigated the molecular basis for this unique host-pathogen relationship. We show that human and murine chlamydial infection tropism is linked to unique host and pathogen genes that have coevolved in response to host immunity. This intimate host-pathogen niche revolves around a restricted repertoire of host species-specific IFN-gamma-mediated effector responses and chlamydial virulence factors capable of inhibiting these effector mechanisms. In human epithelial cells, IFN-gamma induces indoleamine 2,3-dioxygenase expression that inhibits chlamydial growth by depleting host tryptophan pools. Human chlamydial strains, but not the mouse strain, avoid this response by the production of tryptophan synthase that rescues them from tryptophan starvation. Conversely, in murine epithelial cells IFN-gamma induces expression of p47 GTPases, but not indoleamine 2,3-dioxygenase. One of these p47 GTPases (Iigp1) was shown by small interfering RNA silencing experiments to specifically inhibit human strains, but not the mouse strain. Like human strains and their host cells, the murine strain has coevolved with its murine host by producing a large toxin possessing YopT homology, possibly to circumvent host GTPases. Collectively, our findings show chlamydial host infection tropism is determined by IFN-gamma-mediated immunity.

Animals↗
PubMed2005

Chlamydial infection induces pathobiotype-specific protein tyrosine phosphorylation in epithelial cells.

Members of the genus Chlamydia are strict obligate intracellular pathogens that exhibit marked differences in host range and tissue tropism despite sharing a remarkable level of genomic synteny. These pathobiotype differences among chlamydiae are also mirrored in their early interactions with cultured mammalian host cells. Chlamydial attachment and entry is known to trigger protein tyrosine phosphorylation. In this study, we examined the kinetics and pattern of protein tyrosine phosphorylation induced by infection with a comprehensive collection of chlamydial strains exhibiting diversity in host, tissue, and disease tropisms. We report new findings showing that protein tyrosine phosphorylation patterns induced by infection directly correlate with the pathobiotype of the infecting organism. Patterns of protein tyrosine phosphorylation were induced following early infection that unambiguously categorized chlamydial pathobiotypes into four distinct groups: (i) Chlamydia trachomatis trachoma biovars (serovars A to H), (ii) C. trachomatis lymphogranuloma venereum biovars (serovars L1 to L3), (iii) C. muridarum, and (iv) C. pneumoniae and C. caviae. Notably, chlamydia-infected murine and human epithelial cells exhibited the same protein tyrosine phosphorylation patterns; this is indirect evidence suggesting that the phosphorylated protein(s) is of chlamydial origin. If our hypothesis is correct, these heretofore-uncharacterized proteins may represent a novel class of bacterial molecules that influence pathogen-host range or tissue tropism.

Animals↗
PubMed2005

Prevalence of household firearms and firearm-storage practices in the 50 states and the District of Columbia: findings from the Behavioral Risk Factor Surveillance System, 2002.

OBJECTIVES: To examine the prevalence of household firearms and firearm-storage practices in the 50 states and the District of Columbia and estimate the number of children exposed to unsafe storage practices. METHODS: We analyzed data from the 2002 cross-sectional Behavioral Risk Factor Surveillance System survey of 240735 adults from randomly selected households with telephones in the 50 states and the District of Columbia. RESULTS: Nationally, 32.6% of adults reported that firearms were kept in or around their home. The prevalence of adults with household firearms ranged from 5.2% in the District of Columbia to 62.8% in Wyoming (median: 40.8%). The prevalence of adults with loaded household firearms ranged from 1.6% in Hawaii, Massachusetts, and New Jersey to 19.2% in Alabama (median: 7.0%), and the prevalence of adults with loaded and unlocked household firearms ranged from 0.4% in Massachusetts to 12.7% in Alabama (median: 4.2%). Among adults with children and youth <18 years old, the prevalence of loaded household firearms ranged from 1.0% to 13.4% (median: 5.3%), and the prevalence of loaded and unlocked household firearms ranged from 0.3% to 7.3% (median: 2.3%); in each instance, Massachusetts had the lowest prevalence and Alabama had the highest. Findings indicate that approximately 1.69 million (95% confidence interval: 1.57-1.82 million) children and youth in the United States <18 years old are living with loaded and unlocked household firearms. CONCLUSIONS: Substantial state variations exist in the prevalence of household firearms and firearm-storage practices. It is vital that surveillance systems such as the Behavioral Risk Factor Surveillance System continue to monitor the prevalence of household firearms and firearm-storage practices so that future interventions to promote safe storage of firearms can be evaluated and more widely implemented based on their efficacy.

Adult↗
PubMed2004

Examination of population-wide trends in barriers to cancer screening from a diffusion of innovation perspective (1987-2000).

BACKGROUND: Barriers to cancer screening may change over time as screening becomes more widespread. METHODS: Using 1987, 1992, and 2000 National Health Interview Survey data, we examined population-wide trends in barriers to Pap, mammography, and colorectal screening (n =66,452). RESULTS: Lack of awareness was the most common barrier for all screening tests; it decreased by 13.5 percentage points for mammography and by 4.6 percentage points for colorectal screening, but increased by 3.0 percentage points for Pap test from 1987 to 2000. Decreases in not recommended by a doctor were observed for mammography (from 20.5% to 3.7%) and colorectal screening (from 22.3% to 14.2%). Examination of trends in barriers among sociodemographic and health care access subgroups revealed disparities for each screening test. CONCLUSIONS: Although population-wide progress has been made in reducing barriers to screening, lack of awareness, and not recommended by a doctor remain important barriers, especially among traditionally underserved populations.

Adult↗
PubMed2004

State trends in uninsurance among individuals aged 18 to 64 years: United States, 1992-2001.

OBJECTIVES: We analyzed state-specific uninsurance trends among US adults aged 18 to 64 years. METHODS: We used logistic regression models to examine Behavioral Risk Factor Surveillance System data for uninsurance from 1992 to 2001 in 47 states. RESULTS: Overall, uninsurance rates increased in 35 states and remained unchanged in 12 states. Increases were observed among people aged 30 to 49 years (in 34 states) and 50 to 64 years (in 24 states), and increases were also observed among individuals at middle and low income levels (in 39 states and 19 states, respectively), individuals employed for wages (in 33 states), and the self-employed (in 18 states). CONCLUSIONS: Among adults aged 18-64, rates of uninsurance increased in most states from 1992 through 2001. Decreased availability of employer-sponsored health insurance, rising health care costs, and state fiscal crises are likely to worsen the growing uninsurance problem.

Adolescent↗
PubMed2004

Metropolitan-area estimates of binge drinking in the United States.

OBJECTIVES: We estimated adult binge drinking prevalence in US metropolitan areas. METHODS: We analyzed 1997 and 1999 Behavioral Risk Factor Surveillance System data for 120 metropolitan areas in 48 states and the District of Columbia. RESULTS: The prevalence of binge drinking varied substantially across metropolitan areas, from 4.1% in Chattanooga, Tenn, to 23.9% in San Antonio, Tex, (median = 14.5%). Seventeen of the 20 metropolitan areas with the highest estimates were located in the upper Midwest, Texas, and Nevada. In 13 of these areas, at least one third of persons aged 18 to 34 years were binge drinkers. There were significant intrastate differences for binge drinking among metropolitan areas in New York, Tennessee, and Utah. CONCLUSIONS: Metropolitan-area estimates can be used to guide local efforts to reduce binge drinking.

Adolescent↗