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Biomedical subjects

David W Martin

Publications and source records attributed to David W Martin.

6 recordsLinked to original sources
PubMed2006

Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia.

BACKGROUND & AIMS: The nonsteroidal anti-inflammatory drug-activated gene (NAG-1) was identified as a proapoptotic, antitumorigenic protein in vitro, induced by many antitumorigenic and chemopreventive drugs including cyclooxygenase inhibitors. However, its antitumorigenic activity has not been elucidated in vivo. METHODS: Transgenic mice were generated that ubiquitously overexpress human NAG-1 under the control of a chicken beta-actin promoter (CAG). The NAG-1 transgenic mice (NAG-(Tg+)) were characterized, and then the antitumorigenic activity was evaluated with 2 colorectal carcinogenesis models: chemical induction with azoxymethane and genetic induction using the Apc(Min+) mutation. RESULTS: NAG-(Tg+) showed no apparent phenotype other than a reduction in body weight, particularly in males. To examine whether NAG-1 expression would suppress intestinal tumorigenesis, the NAG-(Tg+) mice were treated with the colorectal carcinogen azoxymethane. NAG-(Tg+) mice developed 50% fewer aberrant crypt foci and no tumors, in comparison with nontransgenic littermates. This result demonstrates that expression of this human protein in vivo can suppress chemically induced carcinogenesis in the colon. The NAG-(Tg+) mice were also crossed with Apc(Min+) mice to determine the effect of the transgene on intestinal polyp formation. NAG-(Tg+) mice heterozygous for the Apc(Min+) mutation had a significantly reduced polyp load (60%) compared with nontransgenic Apc(Min+) littermates. CONCLUSIONS: Our results support NAG-1 as an important regulator of intestinal adenoma growth in vivo and suggest that NAG-1 may act as a tumor suppressor gene.

Animals↗
PubMed2005

Phreatophytic vegetation and groundwater fluctuations: a review of current research and application of ecosystem response modeling with an emphasis on great basin vegetation.

Although changes in depth to groundwater occur naturally, anthropogenic alterations may exacerbate these fluctuations and, thus, affect vegetation reliant on groundwater. These effects include changes in physiology, structure, and community dynamics, particularly in arid regions where groundwater can be an important water source for many plants. To properly manage ecosystems subject to changes in depth to groundwater, plant responses to both rising and falling groundwater tables must be understood. However, most research has focused exclusively on riparian ecosystems, ignoring regions where groundwater is available to a wider range of species. Here, we review responses of riparian and other species to changes in groundwater levels in arid environments. Although decreasing water tables often result in plant water stress and reduced live biomass, the converse is not necessarily true for rising water tables. Initially, rising water tables kill flooded roots because most species cannot tolerate the associated low oxygen levels. Thus, flooded plants can also experience water stress. Ultimately, individual species responses to either scenario depend on drought and flooding tolerance and the change in root system size and water uptake capacity. However, additional environmental and biological factors can play important roles in the severity of vegetation response to altered groundwater tables. Using the reviewed information, we created two conceptual models to highlight vegetation dynamics in areas with groundwater fluctuations. These models use flow charts to identify key vegetation and ecosystem properties and their responses to changes in groundwater tables to predict community responses. We then incorporated key concepts from these models into EDYS, a comprehensive ecosystem model, to highlight the potential complexity of predicting community change under different fluctuating groundwater scenarios. Such models provide a valuable tool for managing vegetation and groundwater use in areas where groundwater is important to both plants and humans, particularly in the context of climate change.

Biomass↗
PubMed2003

The genome of herpesvirus papio 2 is closely related to the genomes of human herpes simplex viruses.

Infection of baboons (Papio species) with herpesvirus papio 2 (HVP-2) produces a disease that is clinically similar to herpes simplex virus (HSV-1 and HSV-2) infection of humans. The development of a primate model of simplexvirus infection based on HVP-2 would provide a powerful resource to study virus biology and test vaccine strategies. In order to characterize the molecular biology of HVP-2 and justify further development of this model system we have constructed a physical map of the HVP-2 genome. The results of these studies have identified the presence of 26 reading frames that closely resemble HSV homologues. Furthermore, the HVP-2 genome shares a collinear arrangement with the genome of HSV. These studies further validate the development of the HVP-2 model as a surrogate system to study the biology of HSV infections.

Animals↗
PubMed2002

Herpesvirus papio 2 encodes a virion host shutoff function.

Infection of baboons with herpesvirus papio 2 (HVP-2) produces a disease that is similar to human infection with herpes simplex viruses (HSV). Molecular characterization of HVP-2 has demonstrated that the virion contains a factor which rapidly shuts off host cell protein synthesis after infection. Reduction of host cell protein synthesis occurs in parallel with the degradation of mRNA species. A homolog of the HSV virion host shutoff (vhs) gene was identified by Southern and DNA sequence analysis. The sequence of the HVP-2 vhs gene homolog had greater than 70% identity with the vhs genes of HSV 1 and 2. Disruption of the HVP-2 vhs open reading frame diminished the ability of the virus to shut off protein synthesis and degrade cellular mRNA, indicating that this gene was responsible for the vhs activity. The HVP-2 model system provides the opportunity to study the biological role of vhs in the context of a natural primate host. Further development of this system will provide a platform for proof-of-concept studies that will test the efficacy of vaccines that utilize vhs-deficient viruses.

3T3 Cells↗