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2002
Award Recipients |
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| In 2002, seven Pilot Projects were funded,
for a total of $127,000. |
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| Indoor endotoxin,
allergens, and asthma severity in Los Angeles |
| Investigator(s):
Rob McConnell, M.D., Associate Professor, Department
of Preventive Medicine, USC |
Description:
The role of endotoxin in asthma is not well understood,
and there has been little study of the effect
of relatively low indoor levels of exposure on
asthmatics. However, inflammation is a cardinal
feature of asthma exacerbation. In this pilot
study, we will build on an existing resource,
the LA CASA asthma intervention study, in which
health outcomes and child’s bedding dust
cockroach and house dust allergen levels are measured
repeatedly in the homes of asthmatic children
in Los Angeles.
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Correlation
of air pollution associated deficits in lung function
growth associated with small airways structure
assessed by high res CT |
| Investigator(s):
Frank Gilliland, M.D., Ph.D., Department of Preventive
Medicine, USC |
Description:
Lung function growth is frequently quantified
using spirometry in environmental epidemiologic
studies of air pollution. Many studies have focused
on the effects of acute exporsure on short-term
changes in airway function; however, few have
investigated the long-term effects of chronic
exposure on childhood lung function. Findings
from the Children’s Health Study, a 10-year
longitudinal study of the chronic effects of air
pollution among 6000 children residing in 12 southern
California communities indicate that current levels
of particulate matter, nitrogen dioxide, and vapor
acids are associated with reduced lung function
growth and lower maximum attained measures of
airway flows. The deficits (up to 8%) are largest
and most consistent for FEV1 and MMEF, suggesting
that flows from small airways may be reduced.
The biology underlying these spirometric deficits
has yet to be determined. Recent developments
in lung imaging using High-Resolution CT (HRCT)
now make it feasible to non-invasively study the
structure small airways as small as 2mm in diameter.
These developments make it possible to investigate
the anatomic relationship between air pollution
associated deficits in spirometric measure of
airway flow and permanent changes the structures
of small airway.
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| Examination of DNA
methylation patterns in human cells subject to oxidative
stress |
| Investigator(s):
Joseph G. Hacia,Ph.D., Department of Biochemistry
/ Molecular Biology, USC |
Description:
Differential gene expression plays a major role
in cellular responses to genotoxic stresses such
as exposure to oxidants. DNA methylation is a
fundamental cellular mechanism for modulating
gene expression. Nevertheless, its role in mediating
biochemical responses to genotoxic stresses is
not well understood. In this application, the
hypothesis that DNA methylation changes play a
significant role in cellular responses to oxidative
stress will be tested. In order to accomplish
this, novel oligonucleotide microarrays to increase
the throughput and decrease the costs of fluorescence-based
DNA methylation assays will be utilized. A flexible
platform will be created that will evaluate the
methylation patterns of over 200 genes involved
in disease states or responses to cellular stresses.
The DNA methylation patterns of fibroblast cell
lines subject to controlled levels of oxidative
stress will be determined using this technology.
These fibroblasts will be obtained with donors
from a range of age groups from both genders.
We will create a database of DNA methylation patterns
in these cell lines. This database will be useful
in defining biochemical pathways that are altered
by DNA methylation patterns in response to oxidative
stress. This will provide the basis for larger-scale
studies aimed at studying global DNA methylation
responses to identify biomarkers and biochemical
response pathways associated with exposure to
different environmental stresses or other stimuli.
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| Off-line sampling
of exhaled nitric oxide in respiratory health surveys |
| Investigator(s):
William S. Linn, M.A.; Henry Gong Jr., M.D., Department
of Preventive Medicine, USC |
Description:
Nitric oxide (NO) is an important chemical mediator
in a number of organ systems. In the respiratory
tract, sources, sinks, and actions of NO are incompletely
understood, but empirical studies have shown that
the exhaled concentration of NO provides useful
information about respiratory disease states.
For example, exhaled NO tends to be higher in
asthmatics than in healthy individuals, and lower
in smokers than in nonsmokers. Accordingly, in
the Children's Health Study (CHS) and other large-scale
surveys, exhaled NO measurements could help to
validate questionnaire data concerning asthma
and smoking, and to test hypotheses concerning
acute or chronic respiratory effects of air pollution
and other measurable risk factors. Ideal "on-line"
NO measurement techniques appear too costly for
use in large-scale field surveys. "Off-line"
measurement should allow more cost-effective use
of instrumentation and personnel, but have not
been validated in large studies with multiple
testing sites requiring long-distance transport
of breath samples prior to analysis.
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| A Comparison of
Methods to Measure Cytokines |
| Investigator(s):
Wendy Cozen, D.O., M.P.H., Department of Preventive
Medicine, USC |
Description:
Childhood asthma is increasing worldwide. One
of the explanations may be that children are growing
up increasingly protected from early childhood
infections (the “hygiene hypothesis”)
which results in an altered immune system susceptible
to asthma and allergy later. Evidence for this
is the higher risk of asthma among urban dwelling
children and the inverse association with sibship
size (fewer siblings, the less exposure to infections
when young and the higher the risk of asthma).
A possible mechanism for the hygiene hypothesis
has been proposed. If measurements using the two
methods proposed were correlated it would suggest
that we could evaluate the natural history and
determinants of Th1/Th2 balance from birth through
early childhood using finger sticks as the primary
method of blood collection a very feasible approach.
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| Effects of carcinogen
exposure on DNA rearrangements in human cells |
| Investigator(s):
Robert Schiestel, Ph.D., Department of Pathology,
USC |
Description:
Gross genomic instability such as DNA deletions,
translocations, amplifications etc. is a hallmark
of cancer cells. There is a large body of evidence
coming from our as well as other labs that environmental
exposure to carcinogens as well as genetic cancer
predisposing factors increases the frequency of
genetic instability. We propose to develop an assay
for genome rearrangements based on the variation
of the copy number of DNA repeat. About 20 to 40
copies of a 3.3 kb repeat exists on the ends of
both, chromosomes 4 and 10 and changes in the copy
number occur by deletion or amplification. We propose
to use Pulse Fields Gel Electrophoresis and Flow
Cytometry for DNA sizing to determine the effects
of several carcinogens, including ionizing radiation,
benzo-a-pyrene and benzene on the frequency of such
rearrangements. Such a screening assay would be
extremely useful to detect environmental as well
as genetic predisposing factors for cancer.
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| A Novel Method for
Measurement of Acrolein in Aerosols |
| Investigator(s):
Judith Charles, Ph.D, Department of Environmental
Health, UC Davis |
Description:
As part of the Children’s Health Study (CHS),
the Southern California Particle Center and Supersite
(SPCS) is also investigating the role of quinines,
aldehydes, polyaromatic hydrocarbons (PAHs), and
atmospheric transformation products on chronic health
effects in children. The SPCS is also investigating
whether airway disease and cardiovascular effects
will be more severe during periods of high photochemical
activity in the summer than in periods of low photochemical
activity during the winter. In both projects, there
is interest in measuring acrolein and other carbonyls
that may adversely affect human health. Acrolein
is a component of motor vehicle exhaust, and is
also generated by photooxidation of 1,2-butadiene.
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