Call number: LD2668 .T4 1962 U68

LD2668 .T4 1966 B64 / Master of Science

Call number: LD2668 .T4 1966 F854 / Master of Science

Call number: LD2668 .T4 1984 G58 / Master of Science

Call number: LD2668 .T4 1965 C97 / Master of Science

Call number: LD2668 .T4 1966 R923 / Master of Science

The purpose of this research was to determine the effects of retinoic acid on bovine papillomavirus (BPV) transformed cells. Since BPV transformed cells are able to form colonies in agar and their untransformed counterparts are not, of particular interest was the effect of retinoic acid on this marker. Retinoic acid inhibited the growth of colony forming cells, but the extent of inhibition varied among several cloned cell lines. Retinoic acid inhibited the proliferation of BPV transformed cells and the extent of this inhibition also varied. The copy number of the virus was determined for each of three cell lines by liquid reassociation experiments. The copy number did not change when the cells were treated with RA for a prolonged period of time. Gel electrophoresis and Southern blotting of extrachromosomal DNA from the cell lines revealed the presence of unit length BPV DNA in all three transformed cell lines. The amount of BPV DNA per cell was decreased when the cells were treated with 10⁻⁵ M RA for three days.

The well-known field of engineering psychology, also known as human factors engineering, utilizes psychologists to solve Engineering's problems that concern the behavior of humans in their operation and control of engineering systems such as military aircraft. To limit psychology's relation to engineering this way is, however, counterproductive. Psychology requires a broader conceptualization of engineering psychology, a subfield of psychology, within which the psychologist's major concern is with the behavior of psychoengineering systems that affect the reliability, validity and safety of psychological research and practice. In contrast with human-factor systems, the psychoengineering systems include healthy and unhealthy, human and animal subjects. The affiliated problems are not those of the engineering industry. This study in engineering psychology concerned the safety of two electrical stimulation systems that are used on animals, chiefly dogs, in punishment and escape/avoidance conditioning procedures of psychology. The study referenced two safety questions. First, is the electricity, when applied externally to the ventral neck of the animal, capable of stimulating carotide sinus and vagus nerves to the point of dangerously disrupting systemic blood pressure and sinus rhythm? Second, is the electricity capable of damaging the epidermis when it is applied repeatedly to the same two points of contact? Of forty-two anesthetized dogs, half were tested with a punishment system; the remainder were tested with an escape/avoidance system. Each was stimulated for five seconds, five times, at each of five intensities. Inter-stimulus interval was about thirty seconds. Systemic blood pressures and electrocardiograms (ECG) were recorded. Control and experimental biopsies were taken for histological examinations of electrified and unelectrified specimens. Each animal's neck was examined grossly each day for ten days following the stimulation runs. None of the gross examination reports was positive. An exact binomial test supported the hypothesis that tissue samples from control and experimental biopsies did not differ histologically. Repeated measure ANOVAs were used to detect significant differences in systolic pressures, diastolic pressures, and R to R intervals of the ECG throughout stimulation runs. While there were some statistically significant results, there was no clinical significance, especially with regard to safety hazards.

Splenic and lymph node lymphocytes from Balb/C mice were activated in vitro by the heavy metal cations, Zn⁺⁺ and Hg⁺⁺, as noted by the several-fold increases in ³H-thymidine incorporation at 144 hours of culture. Optimal mitogenic concentrations of Zn⁺⁺ and Hg⁺⁺ were 200 μM and 10 μM, respectively. Data from experiments in which three different methods were used to enrich for either T or B splenic lymphocytes, i.e. cell passage over nylon wool columns, use of athymic Nu/Nu mouse spleen cells, or cell lysis with monoclonal anti-Thy-1 antibody plus complement, suggested that Zn⁺⁺ and Hg⁺⁺ were mitogens for T cells. Removal of macrophages from spleen cells by treatment with carbonyl iron followed by cell passage through nylon wool eliminated the lymphocyte responses to Zn⁺⁺ and to Hg⁺⁺. Moreover, addition of these macrophage-depleted lymphocytes to monolayers of resident peritoneal macrophages restored the lymphocyte responses to these mitogens. Both Zn⁺⁺ and Hg⁺⁺ activated splenic lymphocytes to display lectin-dependent cytotoxicity and to produce gamma interferon. Furthermore, Zn⁺⁺ induced low levels of natural killer activity in spleen cells. In contrast to spleen and lymph node cells, thymocytes and bone marrow lymphocytes did not respond to either cation under standard culture conditions. However, when cultured in the presence of E. coli-derived lipopolysaccharide (LPS) and 2-mercaptoethanol for 144 hours, thymocytes were activated by Zn⁺⁺ (200 μM) but not by Hg⁺⁺. Quantities of LPS as low as 1.0 ng/ml satisfied this culture requirement. Purified interleukin 1 could not replace the helping activity mediated by LPS. Thymocyte subpopulation studies showed that Zn⁺⁺ activated enriched peanut lectin receptor-negative mature thymocytes, but LPS was required for the response. Spleen cells from mice, intraperitoneally injected with ZnCl₂ for 7 to 14 days, were not activated in vivo as assessed by ³H-thymidine incorporation in vitro, nor did they display enhanced responses to T-cell or B-cell mitogens. However, zinc administration had negative effects by decreasing spleen cell numbers by 31% and thymic weight by 59%. A theoretical model is presented in which Zn⁺⁺ and Hg⁺⁺ may mediate their stimulating effects in vitro by altering histocompatibility "self" structures on the surface of lymphocytes and macrophages via interactions with sulfhydryl groups on these structures to which T lymphocytes with receptors for "altered self" structures respond with proliferation or cytotoxicity.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy