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Biomedical subjects

C G Gay

Publications and source records attributed to C G Gay.

10 recordsLinked to original sources
PubMed2003

Challenges and opportunities in developing and marketing vaccines for OIE List A and emerging animal diseases.

Veterinary pharmaceutical products generated 14.5 billion U.S. Dollars (USD) in worldwide sales in 2000, with biological products contributing 16.2 percent or 2.3 billion USD. The leading biological products were foot-and-mouth disease (FMD) vaccines, with 284 million USD in sales, representing 26.4 percent of the entire livestock biological business. Despite the potential opportunities for the biologicals industry, non-vaccination policies and undefined control and eradication strategies have deterred the private sector from significant investments in the research and development of vaccines against List A diseases. The primary research focus remains vaccines for infectious diseases that have an impact on current domestic herd health management systems. Changing the vaccine paradigm, investing in new technologies, and creating the future by integrating into key alliances with producers and regulatory authorities will be paramount in protecting our poultry and livestock industries against highly infectious diseases and potential acts of bioterrorism.

Animal Diseases↗
PubMed1995

Risk analysis for the importation of veterinary biologicals into the United States of America.

International trade in veterinary biological products has been restricted by the following factors: a) concerns that contaminated products could result in the introduction of foreign animal disease agents into the importing country b) differences between countries in the technical requirements for product registration. The provisions of the North American Free Trade Agreement (NAFTA) and the General Agreement on Tariffs and Trade (GATT: now the World Trade Organisation [WTO]) require importation decisions to be science-based and transparent. This requires regulatory agencies to implement valid, credible, and science-based risk analysis models for decision-making. The Veterinary Biologics section of the United States Department of Agriculture, Animal and Plant Health Inspection Service, currently uses a formalized risk analysis model to evaluate the safety risks associated with proposals to field test and license new and biotechnology-derived veterinary biological products. This model for evaluating field tests has been modified to evaluate proposals to import veterinary biological products into the United States of America. The authors describe this risk analysis model, which was specifically designed to evaluate the risks of importing veterinary biological products potentially contaminated with foreign animal disease agents.

Animals↗
PubMed1994

Confirming the safety characteristics of recombinant vectors used in veterinary medicine: a regulatory perspective.

Regulatory guidelines for experimental vaccines should encourage scientists in the biological industry to consider safety at the onset of product development. They should aid scientists to develop the necessary information to confirm conclusively the safety characteristics of the vaccine micro-organism. Moreover, these guidelines should be incorporated into a standardized regulatory process. Veterinary Biologics (VB) provides these guidelines in Summary Information Formats. These Summary Information Formats specify the relevant information to submit with a product licence application for conventional and recombinant vector vaccines. This paper compares two Summary Information Formats to demonstrate that, apart from the construction process, the information required to confirm the safety characteristics of conventional and recombinant vaccines is equivalent. A short discussion on the availability of established safety studies for experimental veterinary vaccines is included.

Animals↗
PubMed1992

Current USDA procedures for licensing biotechnology-derived veterinary biologicals.

The establishment of appropriate procedures for regulating the commercialization of biotechnology products is an international issue which has been debated extensively in many countries. This paper will discuss the current procedures that have been established for the regulation of biotechnology-derived veterinary biologicals within the United States Department of Agriculture (USDA) and more specifically within Biotechnology, Biologics, and Environmental Protection (BBEP) of the Animal and Plant Health Inspection Service (APHIS). These procedures implement recent BBEP regulatory policy that has been developed to ensure risk-based regulation and avoid excessive restrictions that might curtail the development of biotechnology products.

Animals↗
PubMed1991

Regulated expression of PDGF A-chain mRNA in human saphenous vein smooth muscle cells.

Platelet-derived growth factor (PDGF) may be an important regulator of vascular smooth muscle cell (SMC) replication and migration in vivo. Platelets, macrophages, endothelial cells, and SMC are all potential sources of PDGF in the vessel wall. In this study, we have examined the regulation of PDGF gene expression using human SMC cultured in vitro. These cells express transcripts encoding the PDGF A-chain, but not the B-chain. The addition of serum, phorbol ester, acidic fibroblast growth factor, transforming growth factor-beta, or tumor necrosis factor-alpha to serum-starved SMC increased PDGF A-chain mRNA levels. The cytokines interleukin-1 and -6 had no detectable effect. These results indicate that SMC present at sites of injury or inflammation may express elevated levels of PDGF-AA, which could act locally in an autocrine or paracrine manner.

Cells, Cultured↗
PubMed1991

Interleukin 1 regulates heparin-binding growth factor 2 gene expression in vascular smooth muscle cells.

The angiogenic polypeptide heparin-binding growth factor 2 (HBGF-2), or basic fibroblast growth factor, is a mitogen for vascular smooth muscle cells in vitro and in vivo. Smooth muscle cells also synthesize HBGF-2; thus, it may stimulate their proliferation in vivo by both autocrine and paracrine mechanisms. We report here that HBGF-2 gene expression in human saphenous vein smooth muscle cells is induced by interleukin (IL)-1 alpha and IL-1 beta, inflammatory cytokines produced by many cell types in response to a variety of signals. Maximal HBGF-2 mRNA levels are detected 2-4 hr after IL-1 treatment; induction may require de novo protein synthesis and does not occur if transcription is inhibited. Immunoprecipitation analysis indicates that IL-1-stimulated cells also express an increased amount of HBGF-2 protein. Interferon gamma and glucocorticoids, inhibitors of smooth muscle cell proliferation in vitro and in vivo, suppress the induction of HBGF-2 expression by IL-1. These results imply that cytokines released at sites of vascular injury or inflammation may regulate HBGF-2 production by smooth muscle cells. Increased HBGF-2 levels within the vessel wall could play a role in both the smooth muscle cell proliferation and the neovascularization associated with the development of atherosclerotic lesions.

Aorta↗
PubMed1991

The half-lives of platelet-derived growth factor A- and B-chain mRNAs are similar in endothelial cells and unaffected by heparin-binding growth factor-1 or cycloheximide.

Platelet-derived growth factor (PDGF) is mitogenic and chemotactic for vascular smooth muscle cells cultured in vitro, and, thus, may play a role in the smooth muscle cell proliferation and migration that occurs during atherosclerotic lesion development. Two related PDGF polypeptides, designated as the A and B chains, form functionally active PDGF-AA, AB, or BB dimers. The PDGF A- and B-chain genes are both transcribed in human umbilical vein endothelial (HUVE) cells and their expression is regulated by cytokines, growth factors, endotoxin, and phorbol ester. We reported previously that the angiogenic polypeptide heparin-binding growth factor (HBGF)-1 induces PDGF A-chain gene expression, but does not affect PDGF B-chain gene expression. In this study, we determined whether mRNA stabilization contributed to this induction by measuring the half-life of PDGF A-chain mRNA in quiescent, HBGF-1-stimulated, and proliferating HUVE cells. PDGF A-chain mRNA levels increase when quiescent HUVE cells are treated with the protein synthesis inhibitor cycloheximide; therefore, the effect of cycloheximide on PDGF A-chain mRNA decay was also investigated. The half-life of PDGF A-chain transcripts in quiescent cells was approximately 2.4 h and neither HBGF-1 nor cycloheximide significantly altered this decay rate. We also estimated the half-life of PDGF B-chain mRNA under the three different growth conditions and in the absence or presence of cycloheximide. The half-life in quiescent cells was approximately 1.8 h and was unaffected by HBGF-1 or protein synthesis inhibition. Therefore, the PDGF mRNAs have similar decay rates in HUVE cells, even though the 3' untranslated region of B-chain transcripts, but not A-chain transcripts, contains AU-rich sequence motifs postulated to confer rapid turnover in vivo.

Blotting, Northern↗
PubMed1991

Serum, phorbol ester, and polypeptide mitogens increase class 1 and 2 heparin-binding (acidic and basic fibroblast) growth factor gene expression in human vascular smooth muscle cells.

Vascular smooth muscle cell proliferation is regarded as a key early event in the pathogenesis of atherosclerosis. Heparin-binding growth factor (HBGF)-1 and HBGF-2, also referred to as acidic and basic fibroblast growth factor, are potent mitogens for human vascular smooth muscle cells. These cells coexpress HBGF-1 and HBGF-2 and thus represent a vessel wall source for both polypeptides. In this report, we demonstrate that HBGF-1 and HBGF-2 expression is increased when quiescent human smooth muscle cells are treated with fetal bovine serum. The kinetics of HBGF-1 and HBGF-2 mRNA accumulation following serum treatment are distinct. In addition, HBGF-1 transcripts remain elevated for a longer time period; this may reflect the different decay rates of the HBGF-1 and HBGF-2 mRNAs. Serum-inducible HBGF-1 and HBGF-2 mRNA expression does not occur when RNA synthesis is repressed by actinomycin D but can occur in the presence of cycloheximide, an inhibitor of protein synthesis. Immunoprecipitation experiments indicate that serum treatment also increases HBGF-1 and HBGF-2 production. Smooth muscle cells treated with phorbol 12-myristate 13-acetate or certain combinations of polypeptide growth factors also express increased levels of HBGF-1 and HBGF-2 transcripts. Potential sources for these growth factors in vivo include platelets, macrophages, and T lymphocytes; thus, smooth muscle cells located at sites of vascular injury or inflammation may express elevated levels of HBGF-1 and HBGF-2.

Animals↗
PubMed1990

Heparin-binding growth factor-1 stimulation of human endothelial cells induces platelet-derived growth factor A-chain gene expression.

Heparin-binding growth factor-1 (HBGF-1), also known as acidic fibroblast growth factor, is a potent mitogen for a variety of cell types including vascular endothelial and smooth muscle cells. Studies using murine 3T3 fibroblasts have shown that HBGF-1 induces numerous cellular responses such as the tyrosine phosphorylation of specific polypeptides and the increased expression of actin mRNA. Here we report that the addition of HBGF-1 to quiescent human umbilical vein endothelial cells increases the level of platelet-derived growth factor (PDGF) A-chain mRNA but not PDGF B-chain mRNA. In contrast, factors that inhibit endothelial cell proliferation such as phorbol myristate acetate and the cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha increase both PDGF A-chain and B-chain mRNA levels. HBGF-1 induction of PDGF A-chain mRNA expression occurs in the presence of the protein synthesis inhibitor cycloheximide and thus does not require de novo protein synthesis. HBGF-1 also increases c-fos, c-jun, and c-myc mRNA levels; in the presence of cycloheximide, PDGF A-chain and protooncogene mRNA accumulation kinetics are similar. Nuclear run-on experiments indicate that the transcription rate of the PDGF A-chain gene transiently increases after HBGF-1 addition. Immunoprecipitation analysis using PDGF A-chain-specific antibodies indicates that HBGF-1-stimulated cells synthesize and secrete an increased amount of PDGF relative to unstimulated cells. If HBGF-1 can regulate PDGF expression by vascular endothelial cells in vivo, then HBGF-1 availability would be an important component of smooth muscle cell growth control. For example, HBGF-1 within the vessel wall would promote smooth muscle cell proliferation by (a) direct interaction with smooth muscle cell HBGF-1 receptors, and (b) increasing the amount of endothelial cell-derived PDGF available for binding to smooth muscle cell PDGF receptors.

Cell Division↗