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Biomedical subjects

Geoffrey Morgan

Publications and source records attributed to Geoffrey Morgan.

5 recordsLinked to original sources
PubMed2006

Associations between ambient air pollution and daily emergency department attendances for cardiovascular disease in the elderly (65+ years), Sydney, Australia.

There are no reported studies on the effects of ambient air pollution on emergency department (ED) attendances in Sydney, Australia. This study aimed to determine associations between ambient air pollutants and ED attendances for cardiovascular disease (CVD) in those aged 65+ years. We constructed daily time series of hospital ED attendances, air pollutants and meteorological factors for the Sydney metropolitan area from 1 January 1997 to 31 December 2001. We used generalised linear models to determine associations between daily air pollution and daily ED attendances and controlled for the effects of long-term trends, seasonality, weather and other potential confounders. Increased ED attendances for all CVD, cardiac disease and ischaemic heart disease were seen with 24-h particulate pollution, 1-h NO(2), 8-h CO and 24-h SO(2). Air pollutants were associated with decreased ED attendances for stroke. The effects of air pollutants on CVD, cardiac disease and stroke attendances were generally greater in the cool period compared to the warm period. The single-pollutant effects of CO, O(3), NO(2) and SO(2) were essentially unchanged in two-pollutant models. Although air pollution levels in Sydney are relatively low compared to similar cities, we have demonstrated associations between ambient air pollutants and ED attendances for CVD in people aged 65+ years. Our study adds to the growing evidence for the effects of ambient air pollution on CVD outcomes even at relatively low ambient concentrations.

Aged↗
PubMed2004

CD45 isoforms in T cell signalling and development.

The CD45 phosphotyrosine phosphatase is expressed on T cells as multiple isoforms due to alternative splicing. The panoply of isoforms expressed is tightly regulated during T cell development and on mature peripheral T cell subsets following activation. We describe the analysis of comparative CD45 isoform expression levels on thymic and T cell subsets from the C57BL/6 mouse. Only four isoforms were expressed at significant protein levels: CD45R0, CD45RB, CD45RBC and CD45RABC, although trace amounts of others may be present. The expression of CD45RBC was about nine-fold higher on CD8(+) than on CD4(+) peripheral T cells, whereas CD45R0 expression was higher on CD4(+) T cells. We provide a general overview of the current models that have been proposed to explain the molecular actions of the different CD45 isoforms. Achieving a thorough understanding of the biological reasons for the existence and tight regulation of CD45 isoform expression in immune cells remains one of the outstanding challenges in the CD45 research field.

Animals↗
PubMed2003

Alefacept selectively promotes NK cell-mediated deletion of CD45R0+ human T cells.

Modulation of the immune response using immunoglobulin fusion proteins has shown great promise for clinical immunotherapy of autoimmune diseases. Alefacept is an immunoglobulin fusion protein composed of the first extracellular domain of human LFA-3 fused to the hinge, C(H)2 and C(H)3 domains of human IgG(1). Alefacept has previously been reported to inhibit T cell proliferation. Here, we analyzed the effects of alefacept on lymphocytes in vitro and characterized the role of autologous NK cells in its mechanism of action. Alefacept, but not a C(H)2 binding mutant of Alefacept, inhibited CD3-induced T cell proliferation only in the presence of live NK cells, consistent with an important role for FcgammaR engagement. Alefacept caused preferential depletion of CD69+CD45R0+CD25+ T cell subsets. Cytotoxicity assays revealed that alefacept, but not the C(H)2 binding mutant, induced NK cell-mediated death of activated T cells and sorting into CD45R0+ and CD45RA+ subpopulations showed that lymphocyte deletion occurred preferentially in the CD45R0+ subset. Activated CD45R0+ cells expressed higher levels of CD2 than CD45R0- cells, providing a possible explanation for the selective targeting of this subset. Our results suggest that selective targeting of CD45R0+ T cells by NK cells represents a potential therapeutic mechanism of action of alefacept.

Alefacept↗
PubMed2003

Health impacts of pesticide exposure in a cohort of outdoor workers.

We compared mortality of 1,999 outdoor staff working as part of an insecticide application program during 1935-1996 with that of 1,984 outdoor workers not occupationally exposed to insecticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian population, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39-7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16-8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (SMR = 5.27; 95% CI, 1.09-15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized incidence ratio = 20.90; 95% CI, 1.54-284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides.

Adult↗