Bastiaan Hoogendoorn

Context: Ultrafine particulate matter contribution to cardiovascular disease is not known and not regulated. PM up to 500 nm are abundant in urban air and alveolar deposition is significant. Objective: Effects beyond the alveolar barrier within the body or in vitro tissues exposed to particles Methods and results: Databases: MEDLINE; Ovid-MEDLINE PREM; Web of Science; PubMed (SciGlobe). 127 articles. Results in tables: “subject type exposed”, “exposure type”, “technique”. Conclusion: Heart rate, vasoactivity, atherosclerotic advancement, oxidative stress, coagulability, inflammatory changes are affected. Production of reactive oxygen species is a useful target to limit outcomes associated with UFP exposure.

There is emerging evidence for the presence of an extensive microbiota in human lungs. It is not known whether variations in the prevalence of species of microbiota in the lungs may have aetiological significance in respiratory conditions such as asthma. The aim of the study was to undertake semi-quantitative analysis of the differences in fungal species in pooled sputum samples from asthma patients and controls.

Particulate matter (PM) air pollution has significant cardiopulmonary health effects. Serum biomarkers may elucidate the disease mechanisms involved and provide a means for biomonitoring exposed populations, thereby enabling accurate policy decisions on air quality standards to be made. For this review, research investigating association of blood serum biomarkers and exposure to PM was identified, finding 26 different biomarkers that were significantly associated with exposure. Recent evidence links different effects to different components of PM. Future research on biomarkers of effect will need to address exposure by all PM size fractions.

Exposure to ambient particulate air pollution is associated with increased cardiovascular and respiratory morbidity and mortality. It is necessary to understand causal pathways driving the observed health effects, particularly if they are differentially associated with particle size. To investigate the effect of different size ranges of ambient particulate matter (PM) on gene and protein expression in an in vitro model. Normal human tracheobronchial epithelium (NHTBE) three-dimensional cell constructs were exposed for 24 h to washed ambient PM of different sizes (size 1: 7-615 nm; size 2: 616 nm-2.39 µm; size 3: 2.4-10 µm) collected from a residential street. A human stress and toxicity PCR array was used to investigate gene expression and iTRAQ was used to perform quantitative proteomics. Eighteen different genes of the 84 on the PCR array were significantly dysregulated. Treatment with size 2 PM resulted in the greatest number of genes with altered expression, followed by size 1 and lastly size 3. ITRAQ identified 317 proteins, revealing 20 that were differentially expressed. Enrichment for gene ontology classification revealed potential changes to various pathways. Different size fractions of ambient PM are associated with dysregulatory effects on the cellular proteome and on stress and toxicity genes of NHTBE cells. This approach not only provides an investigative tool to identify possible causal pathways but also permits the relationship between particle size and responses to be explored.

Urban air particulate matter (PM) has previously been associated with a variety of adverse health effects. It is now believed that the smallest particles, ultrafine or nanoparticles, are linked to the greatest health effects. The physicochemistry of these particles is likely to provide information regarding their toxicity. Therefore, the aim of this study was to further the understanding of the heterogeneous and changing particle concentrations in urban air, in conjunction with gaining an understanding of the physicochemistry of the particles. A Dekati electrical low-pressure impactor was used to collect the particles and real-time data in a busy traffic corridor in Swansea, Wales, over a period of 10 nonconsecutive weeks. Particle concentrations in the street canyon were analyzed and particle physicochemistries investigated using a variety of techniques. Particle number concentrations were found to vary both diurnally and from day to day in the traffic corridor. Of all particles, the nano to fine size fraction was consistently identified in the highest concentrations (maximum: 140,000 particles cm⁻³). Particle physicochemistry was found to vary as a function of size, with larger particles exhibiting a greater variety of morphologies (and consequently particle types) and associated metals.

A considerable proportion of heritable human phenotypic variation is thought to result from altered gene expression. Unfortunately, it is currently impossible to use bioinformatic analysis to discriminate between DNA sequence variants that are likely to influence gene expression and those that are not. In an attempt to define some of the characteristics of promoter polymorphisms with functional effects on gene expression, we examined 674 haplotypes representing 247 unique gene promoters using a standardized reporter gene assay system. Sequence variants that altered gene expression by 1.5-fold or more were strongly biased toward a location in the core and proximal promoter regions, 50% being within the first 100 bases 5′ to the transcription start site. No bias was seen in the allele frequencies of functional and nonfunctional sequence variants. Only 33% of the functional variants were found in known consensus transcription factor binding sequences or motifs, which suggests that either there are many unknown transcription factor binding motifs or other, unknown mechanisms are involved. The genes with functional polymorphisms that are reported here for the first time include AGTRL2, CAT, CHRNA5, CTSG, CYP2D6, DLD, ERCC1, GABRA1, GABRP, HNRPH3, HIP1, IGKV1-9, KCNJ15, KCNK6, KLK1, MSMB, MYOC, NPY2R, NOTCH4, ORM2, PEDF, PTPRCAP, ST16 (IL24), SULT1A1, and TSHR. Hum Mutat 26(3), 214–223, 2005.

Association has been reported between the C allele of a -759C/T polymorphism in the promoter of the 5-HT2C receptor gene (HTR2C) and antipsychotic-induced weight gain, suggesting that polymorphic HTR2C expression influences this phenotype. The authors tested this polymorphism, and other promoter variants, for effects on HTR2C transcription. Six HTR2C promoter haplotypes constructed from four polymorphisms were cloned into a luciferase reporter gene plasmid. Their transcriptional activities were then compared in two human cell lines. All haplotypes containing the -759C allele showed less transcriptional activity than haplotypes containing the -759T allele. The A allele of a -997G/A polymorphism was also associated with reduced expression. These findings suggest that the -759C allele is functional and results in relative underexpression of HTR2C. Reduced expression of HTR2C mRNA may underlie vulnerability to weight gain following antipsychotic treatment.