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Biomedical subjects

Mark D Moore

Publications and source records attributed to Mark D Moore.

4 recordsLinked to original sources
PubMed2004

Emphysema lung tissue gene expression profiling.

Emphysema occurs in a subgroup of patients with chronic obstructive pulmonary disease and patients with the genetic defect of alpha(1)-antitrypsin deficiency who have a smoking history of many years' duration. Emphysema is generally the result of a chronic and progressive destruction of the alveolar structures, which is believed to be driven by chronic inflammation, infections, oxidative stress, and an imbalance of protease and antiprotease activity. Here, we use microarray technology to characterize the gene expression profile of lung tissue samples obtained from patients with advanced emphysema and that obtained from healthy subjects. We hypothesized that the gene expression profile of emphysema lung tissue is distinct when compared with the expression profile of normal lungs. We report that severely emphysematous tissue is characterized by a global decrease in gene expression and by an increased abundance of transcripts encoding proteins involved in inflammation, immune responses, and proteolysis. Whereas the gene expression profile is to some degree shared between "usual" emphysema and alpha(1)-antitrypsin deficiency-related emphysema, there are statistically significant differences in the modulation of groups of genes associated with protein and energy metabolism, and immune function, which allow distinction between these two emphysema types on the lung tissue level.

Adolescent↗
PubMed2003

Hypoxia induces different genes in the lungs of rats compared with mice.

Different animal species have a varying response to hypoxia. Mice develop less pulmonary artery thickening after chronic hypoxia exposure than rats. We hypothesized that the lung tissue gene expression pattern displayed in hypoxic rats would differ from that of hypoxic mice. We exposed Sprague-Dawley rats and C57BL/6 mice to both 1 and 3 wk of hypobaric hypoxia. Although both species developed pulmonary hypertension, mice showed less pulmonary vascular remodeling than rats. Microarray gene analysis demonstrated a distinct pattern of gene expression between mice and rats when exposed to hypoxic conditions. In addition, some genes appeared to be more responsive at an earlier time point of 1 wk of hypoxia. Hypoxic conditions in the rat induce genes involved in endothelial cell proliferation, repression of apoptosis, and vasodilation. Mice exposed to hypoxic conditions decrease the expression of genes involved in vasodilation and in endothelial cell proliferation. Although we cannot determine whether the differential expression of genes during chronic hypoxia is cause or consequence of the differential pulmonary vascular remodeling, we propose that a balance between over- and under-expression of a selective group of genes may be responsible for lung vascular remodeling and vascular tone control.

Animals↗
PubMed2002

Manipulation of pulmonary prostacyclin synthase expression prevents murine lung cancer.

Inhibition of cyclooxygenase (COX) activity decreases eicosanoid production and prevents lung cancer in animal models. Prostaglandin (PG) I(2) (PGI(2), prostacyclin) is a PGH(2) metabolite with anti-inflammatory, antiproliferative, and antimetastatic properties. The instability of PGI(2) has limited its evaluation in animal models of cancer. We hypothesized that pulmonary overexpression of prostacyclin synthase may prevent the development of murine lung tumors. Transgenic mice with selective pulmonary prostacyclin synthase overexpression were exposed to two distinct carcinogenesis protocols: an initiation/promotion model and a simple carcinogen model. The transgenic mice exhibited significantly reduced lung tumor multiplicity (tumor number) in proportion to transgene expression, a dose-response effect. Moreover, the highest expressing mice demonstrated reduced tumor incidence. To investigate the mechanism for protection, we evaluated PG levels and inflammatory responses. At the time of sacrifice following one carcinogenesis model, the transgenics exhibited only an increase in 6-keto-PGF(1alpha), not a decrease in PGE(2). Thus, elevated PGI(2) levels and not decreased PGE(2) levels appear to be necessary for the chemopreventive effects. When exposed to a single dose of butylated hydroxytoluene, transgenic mice exhibited a survival advantage; however, reduction in alveolar inflammatory response was not observed. These studies demonstrate that manipulation of PG metabolism downstream from COX produces even more profound lung cancer reduction than COX inhibition alone and could be the basis for new approaches to understanding the pathogenesis and prevention of lung cancer.

Animals↗