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Timothy Buckley

Publications and source records attributed to Timothy Buckley.

7 recordsLinked to original sources
PubMed2005

Transfection of tyrosine kinase deleted FGF receptor-1 into rat brain substantia nigra reduces the number of tyrosine hydroxylase expressing neurons and decreases concentration levels of striatal dopamine.

The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK-) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN neurons that expressed tyrosine hydroxylase (TH) was significantly reduced following HSV-1 FGFR1(TK-) intranigral delivery and similar changes were observed after PEI-mediated FGFR1(TK-) transfections. Further, we also observed a significantly lower striatal dopamine content following the PEI transfection of FGFR1(TK-). Thus, we conclude that reduced FGF signaling in the SN of Parkinsonian patients could play a role in the impaired dopaminergic transmission associated with the degenerative disease.

Animals↗
PubMed2005

Home environmental intervention in inner-city asthma: a randomized controlled clinical trial.

BACKGROUND: Airborne pollutants and indoor allergens increase asthma morbidity in inner-city children; therefore, reducing exposure, if feasible, should improve asthma morbidity. OBJECTIVE: To conduct a randomized controlled trial of methods to reduce environmental pollutant and allergen exposure in the homes of asthmatic children living in the inner city. METHODS: After the completion of questionnaires, spirometry and allergen skin tests, home inspection, and measurement of home air pollutant and allergen levels, 100 asthmatic children aged 6 to 12 years were randomized to the treatment group (home-based education, cockroach and rodent extermination, mattress and pillow encasings, and high-efficiency particulate air cleaner) or to the control group (treated at the end of the 1-year trial). Outcomes were evaluated by home evaluations at 6 and 12 months, clinic evaluation at 12 months, and multiple telephone interviews. RESULTS: In the treatment group, 84% received cockroach extermination and 75% used the air cleaner. Levels of particulate matter 10 microm or smaller declined by up to 39% in the treatment group but increased in the control group (P < .001). Cockroach allergen levels decreased by 51% in the treatment group. Daytime symptoms increased in the control group and decreased in the treatment group (P = .04). Other measures of morbidity, such as spirometry findings, nighttime symptoms, and emergency department use, were not significantly changed. CONCLUSIONS: A tailored, multifaceted environmental treatment reduced airborne particulate matter and indoor allergen levels in inner-city homes, which, in turn, had a modest effect on morbidity.

Air Pollution, Indoor↗
PubMed2005

Airborne multidrug-resistant bacteria isolated from a concentrated swine feeding operation.

The use of nontherapeutic levels of antibiotics in swine production can select for antibiotic resistance in commensal and pathogenic bacteria in swine. As a result, retail pork products, as well as surface and groundwaters contaminated with swine waste, have been shown to be sources of human exposure to antibiotic-resistant bacteria. However, it is unclear whether the air within swine operations also serves as a source of exposure to antibiotic-resistant bacterial pathogens. To investigate this issue, we sampled the air within a concentrated swine feeding operation with an all-glass impinger. Samples were analyzed using a method for the isolation of Enterococcus. A total of 137 presumptive Enterococcus isolates were identified to species level using standard biochemical tests and analyzed for resistance to erythromycin, clindamycin, virginiamycin, tetracycline, and vancomycin using the agar dilution method. Thirty-four percent of the isolates were confirmed as Enterococcus, 32% were identified as coagulase-negative staphylococci, and 33% were identified as viridans group streptococci. Regardless of bacterial species, 98% of the isolates expressed high-level resistance to at least two antibiotics commonly used in swine production. None of the isolates were resistant to vancomycin, an antibiotic that has never been approved for use in livestock in the United States. In conclusion, high-level multidrug-resistant Enterococcus, coagulase-negative staphylococci, and viridans group streptococci were detected in the air of a concentrated swine feeding operation. These findings suggest that the inhalation of air from these facilities may serve as an exposure pathway for the transfer of multidrug-resistant bacterial pathogens from swine to humans.

Air Microbiology↗
PubMed2005

Air pollution exposure assessment for epidemiologic studies of pregnant women and children: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research.

The National Children's Study is considering a wide spectrum of airborne pollutants that are hypothesized to potentially influence pregnancy outcomes, neurodevelopment, asthma, atopy, immune development, obesity, and pubertal development. In this article we summarize six applicable exposure assessment lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research that may enhance the National Children's Study: a) Selecting individual study subjects with a wide range of pollution exposure profiles maximizes spatial-scale exposure contrasts for key pollutants of study interest. b) In studies with large sample sizes, long duration, and diverse outcomes and exposures, exposure assessment efforts should rely on modeling to provide estimates for the entire cohort, supported by subject-derived questionnaire data. c) Assessment of some exposures of interest requires individual measurements of exposures using snapshots of personal and microenvironmental exposures over short periods and/or in selected microenvironments. d) Understanding issues of spatial-temporal correlations of air pollutants, the surrogacy of specific pollutants for components of the complex mixture, and the exposure misclassification inherent in exposure estimates is critical in analysis and interpretation. e) "Usual" temporal, spatial, and physical patterns of activity can be used as modifiers of the exposure/outcome relationships. f) Biomarkers of exposure are useful for evaluation of specific exposures that have multiple routes of exposure. If these lessons are applied, the National Children's Study offers a unique opportunity to assess the adverse effects of air pollution on interrelated health outcomes during the critical early life period.

Air Pollutants↗
PubMed2005

Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods.

CNS gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. One such disorder is Parkinson's disease (PD), in which dysfunction of several different metabolic processes has been implicated. Here we review the literature on gene transfer systems based on herpes simplex virus type 1 (HSV-1) and non-viral polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also assess the usefulness of various CNS gene delivery methods and present some of our own data to exemplify such usefulness. Our data result from vectors stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated 1 week and/or 1 month post injection using histochemical methods to assess recombinant ss-galactosidase enzyme activity. Gene transfer using PEI or calcium phosphate-mediated transfections was observed for both methods and PEI was comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery was markedly increased when packaged with a helper virus and was similar to the expression profile achieved with a full-size replication-defective HSV-1 recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated gene transfer could facilitate assessment of the biological effects induced by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling thought to occur in Parkinson's disease.

Animals↗
PubMed2002

The ability of hospital ventilation systems to filter Aspergillus and other fungi following a building implosion.

OBJECTIVES: To assess the ability of hospital air handling systems to filter Aspergillus, other fungi, and particles following the implosion of an adjacent building; to measure the quantity and persistence of airborne fungi and particles at varying distances during a building implosion; and to determine whether manipulating air systems based on the movement of the dust cloud would be an effective strategy for managing the impact of the implosion. DESIGN: Air sampling study. SETTING: A 976-bed teaching hospital in Baltimore, Maryland. METHODS: Single-stage impactors and particle counters were placed at outdoor sites 100, 200, and 400 m from the implosion and in five locations in the hospital: two oncology floors, the human immunodeficiency virus unit, the cardiac surgical intensive care unit, and the ophthalmology unit. Air handling systems would operate normally unless the cloud approached the hospital. RESULTS: Wind carried the bulk of the cloud away from the hospital. Aspergillus counts rose more than tenfold at outdoor locations up to 200 m from the implosion, but did not increase at 400 m. Total fungal counts rose more than sixfold at 100 and 200 m and twofold at 400 m. Similar to Aspergillus, particle counts rose several-fold following the implosion at 100 and 200 m, but did not rise at 400 m. No increases in any fungi or particles were measured at indoor locations. CONCLUSION: Reacting to the movement of the cloud was effective, because normal operation of the hospital air handling systems was able to accommodate the modest increase in Aspergillus, other fungi, and particles generated by the implosion. Aspergillus measurements were paralleled by particle counts.

Air Conditioning↗