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Biomedical subjects

A M Lewis

Publications and source records attributed to A M Lewis.

At least 19 recordsLinked to original sources
PubMed2001

Developing an approach to evaluate the use of neoplastic cells as vaccine substrates.

Advances in technology, emerging infectious diseases and accumulating knowledge of the mechanisms of neoplastic development are stimulating the need to develop a regulatory management plan that can be used to evaluate different types of neoplastic cells as possible substrates for vaccine development. To address this challenge, CBER is developing an approach, based on issue identification, issue-based model development and validation, and, where possible, a quantitative risk evaluation, as a basis for regulatory guidance on the use of neoplastic cell substrates for the manufacture of viral vaccines. The issues or concerns that have been identified with the use of neoplastic cell substrates include vaccine contamination with viable human tumour cells or adventitious agents, the possible risks associated with residual cell-substrate DNA or proteins in the vaccine, possible vaccine virus interactions with the cell substrate, and possible uncertainties associated with the instability of the neoplastic cell genome.

Neoplasms↗
PubMed2000

Genetic variation in the bovine myostatin gene in UK beef cattle: allele frequencies and haplotype analysis in the South Devon.

Work on Belgian Blue cattle revealed that an 11 base pair (bp) deletion within the bovine myostatin gene (GDF8) is associated with the double-muscled phenotype seen in this breed. Investigations focusing on other European breeds known to show double-muscling identified several mutations within the coding region of the gene associated with the double-muscled phenotype in different breeds. The number of mutations found suggest that myostatin is highly variable within beef cattle. Variations that alter the structure of the gene product such that the protein is inactivated are associated with the most pronounced form of double-muscling as seen in the Belgian Blue. However, other mutations may have a less extreme affect on muscle development. While overt double-muscling gives rise to a high incidence of dystocia (calving difficulty), it is possible that some variants may give enhanced muscling, but with limited calving problems. We describe sequence analysis of the myostatin gene in ten beef breeds commonly used in the UK and show that the 11-bp deletion responsible for double-muscling in the Belgian Blue is also present in the South Devon cattle population. Allele frequencies and haplotypes in the South Devon and a polymerase chain reaction (PCR) based test for the deletion are described. PCR amplification across the deleted region provides a quick and effective test with clear identification of heterozygous individuals. We discuss our results with regard to the effect of genotype on phenotype and differences observed between the Belgian Blue and the South Devon.

Animals↗
PubMed1999

Quantitative electron microscopic study of the hypoxic fetal sheep heart.

In order to determine the effects of chronic, high-altitude hypoxia on the ovine fetal heart, we exposed pregnant ewes to 3,820 m beginning at 30 days gestation. We previously showed that following approximately 110 days of hypoxia the fetal heart showed significant reduction in cardiac output (76% of control) and contractility, and elevated levels of citrate synthase and lactate dehydrogenase. To investigate ultrastructural influences on these observed physiologic changes at altitude, we hypothesized that the volume densities of myofibrils and mitochondria, and glycogen content would be reduced in the ovine fetal heart and that this may contribute to contraction and cardiac output deficits in hypoxia. Mitochondria and myofibril volume density were determined by standard point-counting techniques and glycogen content was determined by biochemical analysis. The glycogen content from the hypoxic right ventricle (4.8 +/- 0.3%) was significantly lower than in control right ventricle (6.8 +/- 0.5%) and both left ventricles (hypoxia, 7.2 +/- 0.5; control, 7.8 +/- 0. 4%). Total mitochondrial volume density was also significantly reduced following hypoxia (15.5 +/- 0.7%) compared to controls (16.9 +/- 0.4%). As is common in the ovine fetal heart, the myofibril volume density of the right ventricle from both groups was significantly higher than the left ventricle (RV, 58.6 +/- 1.6; LV 54.3 +/- 0.9%). However, it was not different between control and high altitude. In support of our hypothesis, we may speculate that deficits in the quantity of myocyte glycogen and mitochondria contribute to the observed reduction in cardiac output and contractility, despite the upregulation of citrate synthase and lactate dehydrogenase. In contrast, myofibril volume density was unchanged.

Altitude↗
PubMed1999

Evaluating virus-transformed cell tumorigenicity.

The tumorigenicity of adenovirus (Ad) 12-transformed mouse cells was evaluated by analyzing the relationship of tumor cell dose to tumor incidence and tumor latency. The tumor producing dose 50% endpoint values used to define these relationships remained stable during 52 weeks of serial passage in tissue culture and were not determined by low frequency events within the cell population. The data from these analyses suggest that the phenotype of Ad12-transformed mouse cells is influenced by two set of traits--those traits that determine the threshold number of cells required for tumor formation and those that extend the cell dose-dependent tumor latency period. Both traits are established independently of cell immortalization, and both can be influenced by the immunological status of tumor-challenged animals. These observations were verified by using mouse cells transformed by Ad5 and SV40. The biological and molecular processes that contribute to these traits remain to be determined. The approach developed by this analysis provides a reliable, quantitative means of evaluating endogenous traits that determine transformed cell tumorigenicity. This method can also be used to test the effects of tumor cell manipulations or changes in host response that could alter expression or detection of these neoplastic cell traits.

Adenoviridae↗
PubMed1999

The pros and cons of isolation and containment.

This paper is a review of isolation and containment models, policies and procedures. The arguments for and against various practices are outlined. The psychological effects of isolating patients in single rooms and new ideas for staff intervention are discussed. A modern, flexible approach is suggested.

Hospitals, Public↗
PubMed1999

Effects of long-term, high-altitude hypoxia on the capillarity of the ovine fetal heart.

To determine the effect of chronic hypoxia on myocardial capillarity, we exposed pregnant ewes to an altitude of 3,820 m from day 30 to day 139 of gestation and compared the fetus to low-altitude (approximately 300 m) controls. We hypothesized that capillarity would increase in the hypoxic myocardium to optimize oxygen and metabolite flux to hypoxic tissues. Fetal hearts were fixed by retrograde aortic perfusion and processed for microscopy and stereological evaluation. Fiber cross-sectional area and capillary density were measured and standardized to sarcomere length. Capillary volume density and capillary diameter were measured, capillary-to-fiber ratio and capillary length density were calculated, and the capillary anisotropy coefficient was obtained from a table of known values. Capillary-to-fiber ratio, capillary volume density, and the capillary anisotropy coefficient were not different between hypoxia and control groups. Capillary diameter was significantly larger in the right compared with the left ventricle of hypoxic but not control hearts; fiber cross-sectional area tended to be larger in the right ventricle of both groups, but this was not significant. As a result of larger fiber size, capillary density and capillary length density were significantly smaller in the right ventricle of hypoxic but not control fetal hearts. Contrary to our hypothesis, the ovine fetus does not show morphological adaptation in the myocardium after approximately 109 days of high-altitude hypoxic stress.

Altitude↗
PubMed1998

FDA "reform"?

Explore the source record for details and available documents.

Budgets↗
PubMed1998

Safety of viral DNA in biological products.

Data from studies of the infectivity of DNA injected directly into laboratory animals are used to estimate the potential infectivity risk of residual DNA in biological products. The potential for some novel products to contain infectious quantities of residual cellular DNA is discussed, and further study of this subject is suggested.

Animals↗