Biomedical subjects

Denny Liggitt

Publications and source records attributed to Denny Liggitt.

21 records · Page 2Linked to original sources

PubMed2002

Local role for tumor necrosis factor alpha in the pulmonary inflammatory response to Mycobacterium tuberculosis infection.

The local intrapulmonary role of tumor necrosis factor alpha (TNF-alpha) in a protective host response during acute and chronic infection with Mycobacterium tuberculosis is incompletely understood. To directly assess its role in the intrapulmonary immune response, we compared the responses of transgenic mice with a local pulmonary blockade of TNF-alpha (SPCTNFRIIFc mice) to mice with globally inhibited TNF-alpha (TNFRKO mice) and mice with normal immune systems (control mice). Consistent with previous reports, 100% of TNFRKO mice died by 28 days after aerosol infection, and these mice had markedly increased numbers of bacteria and widespread tissue necrosis in their lungs compared to controls. The median survival time of the SPCTNFRIIFc mice was 142 days, and 75% died by 180 days. Even though the numbers of bacteria in the lungs of the SPCTNFRIIFc mice were marginally increased compared to controls, these mice had a persistent neutrophilic inflammatory response and increased expression of proinflammatory cytokines (interleukin-1 alpha/beta [IL-1 alpha/beta], IL-18, gamma interferon, IL-6, and macrophage migration inhibitory factor) and chemokines (eotaxin, macrophage inflammatory protein 1 alpha/beta, gamma interferon-inducible protein 10, macrophage chemotaxic protein 1, and TCA-3) in their lungs. These studies with the SPCTNFRIIFc mice provide direct evidence for the local importance of TNF-alpha in the proper regulation of host defense to M. tuberculosis. The studies also suggest that when the local actions of TNF-alpha are selectively impaired in the lungs, tissue destruction and death ensue, at least in part, due to persistent expression of proinflammatory mediators that would normally be downregulated.

Animals↗

PubMed2002

What is your diagnosis?: Multifocal subcutaneous tumors in a young male baboon.

A juvenile male baboon (Papio cynocephalus anubis), while being held in quarantine prior to research assignment at the Washington National Primate Research Center (WaNPRC), presented with three soft tissue masses on the right elbow, wrist, and knee on routine physical examination. The masses were subcutaneous and did not appear to cause any discomfort to the animal. An excisional biopsy of the knee mass was submitted for histopathologic analysis and found to be poorly defined, rapidly growing, and of undetermined histogenesis. Euthanasia was elected, and a full necropsy done with samples collected for histopathologic analysis. By immunohistochemistry, the "large" cells in the masses were suggestive of a mesenchymal, nonmacrophage origin because of their being positive for vimentin and negative for cytokeratin and the macrophage maturation marker CD68. Eosinophilic intracytoplasmic inclusions were seen on HE-stained sections and corresponded to aggregates of ovoid to brick-shaped viral particles on transmission electron microscopy (TEM), which proved to be the key diagnostic tool for this case. The masses were determined to be Yaba monkey tumor virus (YMTV)-induced "benign histiocytomas" by TEM.

Animals↗

PubMed2002

Delivery of deoxyribonucleic acid (DNA) to somatic cells: an overview of species and strain-related responses.

There is great potential in successful delivery of genetic material to somatic cells of animals and humans, not only to treat genetic deficiencies, but also to provide more effective therapies and vaccines. Concerted effort has been mounted over the past decade to validate the concept of gene-based therapy. Delivery of genes in vitro via multiple methods has demonstrated the biologic usefulness of the basic concept. However, application of similar gene delivery strategies to whole animal systems has been more difficult. Much of the complexity associated with gene delivery involves encounters with host biological barriers, including innate and acquired host responses to exogenous DNA, as well as specifically encoded proteins. Delivery of genetic material to somatic cells in vivo is a multi-factorial event involving variables in formulation, route, and dose, and target species or strain. In vivo expression of these variables can result in conflicting findings with regard to gene expression and toxicity. These findings may compromise the predictive reliability of interstrain and, particularly, interspecies studies. This review will address representative in vivo somatic cell transfection modalities, variability in species and strain responses following delivery of nucleic acids, and some of the potential mechanisms involved.

Animals↗