Comment on "vehicle self-pollution intake fraction: children's exposure to school bus emissions".
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Biomedical subjects
Publications and source records attributed to Christopher M Long.
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Advances in molecular diagnostics have led to an increased interest in expanding population-based screening to include genetic diseases that occur outside the newborn period. Hereditary hemochromatosis may be a candidate for large-scale screening in populations with a high prevalence of the common HFE mutations. To determine race-specific frequencies of the HFE mutations, C282Y and H63D, the authors applied an automated, high-throughput genotyping method to dried blood spot samples from a representative population of California newborns. In this sample of 3989 newborns, C282Y and H63D allele frequencies were highest in white (C282Y: 5.5 +/- 0.5%; H63D: 13.4 +/- 0.76%) and Hispanic (C282Y: 1.8 +/- 0.29%; H63D: 11.9 +/- 0.72%) newborns, and lowest in black (C282Y: 1.3 +/- 0.25%; H63D: 3.0 +/- 0.38%) and Asian (C282Y 0.5 +/- 0.16%; H63D 2.9 +/- 0.37%) newborns. The estimated prevalence of C282Y homozygotes in this multiracial population is 1.4/1000. As additional genetic and environmental risk factors for HHC are identified, neonatal screening may become an acceptable strategy to follow susceptible individuals and prevent clinical disease.
OBJECTIVE: We sought to address the toxicology literature on carbon black (CB) since 1996, when IARC reclassified CB from group 3 to group 2B. METHODS: We reviewed epidemiology and laboratory studies from 1996 to 2006, focusing on new analyses of worker populations, on species differences in tumorigenicity of poorly soluble particles, and on the role of particle-bound organics in tumorigenicity. RESULTS: Some epidemiology studies have reported positive associations between cancer risk and worker's possible exposure to CB, but larger studies, in more highly exposed populations, have not shown consistent patterns of either elevated risk or dose-response. High levels of inhaled CB were linked with rat lung tumors in 1996, but today scientists increasingly recognize that rats exhibit a unique lung tumor response to all inert inhaled particles that is unlikely to be relevant to humans. On mechanism of action, new reports have continued to show that CB has a high surface area of elemental carbon, and a low quantity of organic material, which is poorly bioavailable. CONCLUSION: Overall, the new epidemiological evidence decreases concerns for cancer risk compared with pre-1996 evidence. Laboratory studies support a conclusion that the mechanism of tumorigenicity of CB in rats is no different from that of any poorly soluble particle, ie, toxicity results from the particle overload per se, and not from the particles' chemistry. Thus, research published after 1996 has not identified an increase in support for CB cancer risk, but rather, points to limited and inadequate evidence for carcinogenicity.
We fabricated and evaluated high-throughput kinetic thermal cyclers with 768-reaction capacity for kinetic polymerase chain reaction (kPCR)-based genotyping and kinetic reverse transcription (kRT)-PCR-based transcript quantitation. The system uses dye-based detection with ethidium bromide and a single DNA polymerase-based PCR or RT-PCR assay. Allele-specific detection of the two most common hereditary hemochromotosis mutant alleles, C282Y and H63D, was reliably measured by kPCR using human DNA templates as low as 10 genome equivalents per assay. Transcript profiling was performed for 16 yeast transcripts ranging in intracellular abundance over four orders of magnitude. Standard deviations of the PCR cycle threshold values determined from multiple kRT-PCR assays in three different instruments ranged from 0.11 to 0.97 PCR cycles and were reproducible, transcript specific, and instrument independent. The effects of the sin3, gal11, and snf2 knockout mutations on expression of 385 yeast genes were evaluated by kRT-PCR and compared to published values determined by high-density oligonucleotide array and/or microarray analysis for snf2 and sin3. The 768-reaction kinetic thermalcyclers, each with a capacity for more than a half million assays per year, are well suited to genomics applications such as single nucleotide polymorphism/disease association studies and genomewide transcription profiling where high sensitivity and accuracy are required.
Six homes in the metropolitan Boston area were sampled between 6 and 12 consecutive days for indoor and outdoor particle volume and mass concentrations, particle elemental concentrations, and air exchange rates (AERs). Indoor/outdoor (I/O) ratios of nighttime (i.e., particle nonindoor source periods) sulfur, PM2.5 and the specific particle size intervals were used to provide estimates of the effective penetration efficiency. Mixed models and graphical displays were used to assess the ability of the I/O ratios for sulfur to estimate corresponding I/O ratios for PM2.5 and the various particle sizes. Results from this analysis showed that particulate sulfur compounds were primarily of outdoor origin and behaved in a manner that was representative of total PM2.5 in Boston, MA. These findings support the conclusion that sulfur can be used as a suitable tracer of outdoor PM2.5 for the homes sampled in this study. Sulfur was more representative of particles of similar size (0.06-0.5 microm), providing evidence that the size composition of total PM2.5 is an important characteristic affecting the robustness of sulfur-based estimation methods.