David A. Sterling

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk

Deletions on human chromosome 8p22–23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.

The Relationship Between School Absence, Academic Performance, and Asthma Status

BACKGROUND Children with asthma experience more absenteeism from school compared with their nonasthma peers. Excessive absenteeism is related to lower student grades, psychological, social, and educational adjustment. Less is known about the relationship between the presence of asthma and the academic achievement in school-aged children. Since students with asthma miss more days from school, this may negatively impact their academic achievement. The goal of this study was to investigate the relationships between absenteeism, presence of asthma, and asthma severity level with standardized test level performance in a predominantly African American urban school district. METHODS A cross-sectional analysis was conducted of 3812 students (aged 8-17 years) who took the Missouri Assessment Program (MAP) standardized test during the 2002-2003 academic year. RESULTS After adjustment for covariates, a significant inverse relationship was found between absenteeism and test level performance on the MAP standardized test in all children (F = 203.9, p < .001). There was no overall difference in test level achievement between those with and without asthma (p = .12). Though not statistically different, those with persistent asthma showed a modestly increased likelihood of scoring below Nearing Proficient compared with those with mild intermittent asthma (adjusted odds ratio = 1.93, 95% confidence intervals = 0.93-4.01, p = .08). CONCLUSIONS A negative impact of absenteeism on standardized test level achievement was demonstrated in children from an urban African American school district. Children with asthma perform the same academically as their nonasthma peers. However, those with persistent asthma show a trend of performing worse on MAP standardized test scores and have more absence days compared with other students. More research is warranted on the effects of persistent asthma on academic achievement.

Pollen and fungal spores indoor and outdoor of mobile homes

BACKGROUND Allergenic diseases triggered by aeroallergens extract a health cost in quality of life and in economic impact. People generally spend 90% to 95% of their time indoors, so understanding the environmental factors that affect the presence of aeroallergens indoors are important in understanding health impact and potential intervention methods. OBJECTIVE Describe the relationship of indoor airborne pollen and fungal spores in occupied mobile homes with outdoor concentrations and other environmental factors within geographically diverse areas of Texas. METHODS Airborne pollen and fungal spores were collected during the daytime with RotoRod samplers indoor and outdoor of mobile homes in Houston and El Paso, Texas. Samples were counted simultaneously with a dual eyepiece microscope and identified morphologically and through staining techniques. RESULTS Geometric mean concentrations (counts/m3) indoors and outdoors for pollen, respectively, were Houston 7.1 and 196.4; and El Paso 17.5 and 71.5. Geometric mean concentrations (counts/m3) indoors and outdoors for spore, respectively, were Houston 98.5 and 196.4; and El Paso 36.9 and 71.5. Indoor to outdoor ratios (I/O) for pollen and fungal spores were found to be higher on average than has been previously reported. Modeling of predictive factors in Houston demonstrate that 62% and 41% of indoor levels of pollen and fungal spores, respectively, can be explained by their corresponding outdoor levels. These data suggest that the many factors associated with individual exposure to airborne pollen and fungal spores indoors are under the control of the occupant, and may additionally be influenced by the physical characteristics of mobile homes, in particular the high surface area to volume ratio and restricted flow patterns.

Relationship between lead mining and blood lead levels in children.

The authors studied blood lead levels of 226 randomly selected children, aged 6-92 mo, who lived in either a lead-mining area or a nonmining area, and 69 controls. The authors sought to determine to what extent mining activities contributed to blood lead levels in the children. The mean blood lead levels in the study and control groups were 6.52 microg/dl and 3.43 microg/dl, respectively. The corresponding proportions of children with elevated blood lead levels were 17% and 3%. Soil and dust lead levels were up to 10 times higher in the study than the control group. Elevated blood lead levels appeared to result from exposure to both lead-mining waste and lead-based paint. Mining waste was the cause of the higher prevalence of elevated blood lead levels in these children.

COPD Is Associated With a Macrophage Scavenger Receptor-1 Gene Sequence Variation

BACKGROUND Macrophages play an important role in COPD. We genotyped at-risk smokers to evaluate the role of polymorphisms in the macrophage scavenger receptor-1 gene (MSR1) in COPD susceptibility and related measures of lung function. Then, in macrophages from donors with specific MSR1 genotypes, we determined the effect of MSR1 single nucleotide polymorphisms (SNPs) on macrophage function by examining in vitro adhesion, receptor expression, and cell number in culture as an index of increased survival/reduced apoptosis. METHODS Smokers (> or = 20 pack-years) who were > 40 years (n = 714) were genotyped for seven SNPs; one nonsense change (ex6R293x_C/T), four missense changes (ex4V113A_T/C, ex4P174Y_G/T, ex11H441R_A/G, and in the ligand binding site ex6P275A_C/G), -176511_A/G in the promoter region, and IVS5-59_C/A in the intron. Nonsmoking healthy volunteers (n = 85) were genotyped, and peripheral blood monocytes were isolated from seven P275A_CG/GG and eight P275A_CC controls and cultured to generate monocyte-derived macrophages (MDM). The effectiveness of trypsin and scraping to dislodge MDM was scored on a four-point subjective scale. MDM were counted on a Z1 particle counter and surface expression of MSR1 was determined by fluorescence-activated cell sorting analysis using secondary staining of antibodies against human macrophage scavenger receptor (MSR1). RESULTS The MSR1-coding SNP P275A was associated with susceptibility to COPD in smokers (P < .005) and a lower percent predicted (pp) FEV(1), FEV(1)/FVC, and pp forced expiratory flow (FEF)(25-75) (P = .03). P275A_CG/GG was also associated with increases in maintenance of cell number in culture (increased survival/reduced apoptosis), MSR1 expression, and adhesion of macrophages to plastic in vitro (P < .05). CONCLUSIONS The MSR1 association with COPD susceptibility, COPD-related measures of lung function, and abnormalities of macrophage function may account for significant COPD morbidity.

Influence of Season and Temperature on the Relationship of Elemental Carbon Air Pollution to Pediatric Asthma Emergency Room Visits

Previous studies have demonstrated an association between air pollution and asthma exacerbation. Less understood is the effect of elemental carbon (EC), and the interaction of EC with temperature, on increases in pediatric asthma emergency department visits and how these relationships change across the seasons in a metropolitan area with several industries and relatively low air pollution. Measurements of EC, ozone (O3), sulfur dioxide (SO2), and total oxides of nitrogen (NOx) were available from the St. Louis EPA Supersite for June 1, 2001 to May 31, 2003. We obtained ICD-9 information on 281,763 pediatric ED visits from 27 hospitals in the St. Louis, MO metropolitan area. The relationship between EC and pediatric asthma ED visits, controlling for season, weekend exposure, allergens, and other pollutants known to exacerbate asthma, was assessed using Poisson generalized estimating equations using a 1-day lag between exposure and ED visit. We evaluated the interaction of EC and temperature and EC and weekend vs. weekday exposure. An interaction effect existed between EC and temperature for 11–17-year-olds during the summer and winter seasons. During the summer, a 0.10 μg/m3 increase in EC resulted in a 9.45% increase in asthma ED visits among 11–17-year-olds (95%CI = 1.02,1.17) at the median seasonal temperature (86.5°F). This risk increased with increasing temperature. During the winter, a 0.10 μg/m3 increase in EC resulted in 2.80% increase in asthma ED visits among 11–17-year-olds (95%CI = 1.01,1.05) at the median seasonal temperature (43.3°F). This risk increased with decreasing temperature. Among 11–17-year-olds, daily number of asthma ED visits is associated with increased levels of EC at higher temperatures in the summer and lower temperatures in the winter.

Indoor air quality and health in two office buildings with different ventilation systems

Abstract Measurements of indoor air pollutants were taken in (1) an air conditioned and (2) an adjacent, naturally ventilated office of a public sector organization. Self-administered questionnaires on the work environment and health were distributed to all workers. No differences in concentrations of carbon monoxide, carbon dioxide, ozone, and total oxidants were found between buildings. Concentrations of formaldehyde, volatile organic compounds, and respirable particulates were higher in the air conditioned offices. Symptoms of sleepiness, nasal irritation, concentration difficulties, cold/flu-like symptoms, and eye focusing problems were significantly more prevalent in the air conditioned offices. Symptoms of sleepiness, nasal irritation, concentration more prevalent among women than men. Passive smoking was associated with symptom prevalence, but alcohol, tea, and coffee consumption was unrelated. No significant correlations between pollutant concentrations and symptom prevalence were found, however, recalled reports of leaving work early because of feeling ill were significantly correlated with formaldehyde levels in the air conditioned building.

Dichloroacetonitrile, a by-product of water chlorination, induces aneuploidy in Drosophila

Nitriles have been shown to be potent inducers of aneuploidy in yeast and Drosophila test systems. Haloacetonitriles are by-products of water chlorination that have been shown to be mutagenic and carcinogenic following topical application. In this report we show that dichloroacetonitrile, but not dibromoacetonitrile, is an effective inducer of aneuploidy in oocytes of Drosophila melanogaster. Following inhalation exposure of ZESTE adult females, dichloroacetonitrile (8.6 ppm) induced highly significant increments in the frequencies of sex chromosome loss and gain. Sodium cyanide was also found to be a highly effective inducer of germline aneuploidy, suggesting that cyanide toxicity may contribute to potency of nitriles as inducers of aneuploidy.

Examining the Consulting Physician Model to Enhance the School Nurse Role for Children With Asthma

BACKGROUND The Centers for Disease Control and Preventions Strategies for Addressing Asthma Within a Coordinated School Health Program recommends a consulting physician for schools to help manage asthma. The literature examines the effects when a school nurse is present, but the addition of a consulting physician is not well understood. The purpose of this study is to assess the effect of having a consulting physician on school absenteeism and children sent home due to health reasons for children with asthma and all children pooled together. METHODS A 2-year preimplementation group cohort and 1-year implementation group cohort of grades K-6 in an urban school district were used to determine the impact of a consulting physician on school absenteeism for children with asthma and all children pooled together. RESULTS A consulting physician was significantly associated with reduced missed school days for children with asthma and all children as a group. All children pooled together were 44% more likely (OR = 1.44, 95% CI = 1.31-1.58) to be sent home without the consulting physician. There was a reduction from 13.8% to 12.6% of sent home events in children with asthma. CONCLUSIONS Having consulting physicians in school districts appears to be associated with fewer days of school absence. The results provide additional evidence and suggest that more research is required to determine if this association is valid and to better understand the cause of such an association.

A Soiling System for Evaluation of House Dust, Allergens, and Lead Retention on Carpets and Other Surfaces

Artificial soiling of carpeted or other floor surfaces has several important applications in human exposure assessment and textile research including evaluation of textile properties, sampling devices, and cleaning regimens. A method was developed and validated to deposit uniform and reproducible known quantities of house dust, allergens, and leaded dust on carpets. The soiling apparatus consisted of a 100 cm x 60 cm inclined steel track and a plastic cylinder, with a series of staggered holes, that contains a known volume of reference house dust. After deposition, the dust is embedded by dragging a steel rod over the carpet surface. Deposition tests were performed with bulk house dust, sodium chloride, and house dust with reference quantities of dust mite allergen and lead. The apparatus deposited equivalent (arithmetic mean) amounts of dust, sodium chloride, and dust mite allergen on the front and back halves of test carpets. The introduction of inert fumed silica to the reference sample aided in dispersal of dust over test surfaces. Little to no variation in mean deposition was found within or between 4 days of testing. Using a grid containing weighing boats under the apparatus, spatial deposition was found to vary across a 92 x 46 cm surface by 13 percent. The apparatus deposited reproducible mean quantities of bulk dust on test surfaces from 7 g/m2 to 28 g/m2 with a coefficient of variation ranging from 4-6 percent. The apparatus could be altered to deliver smaller or larger amounts of dust.