It has been shown by various investigators that reserpine and certain other rauwolfia alkaloids can antagonize digitalis-induced cardiac arrhythmias (Boyaji and Nash, 1965; Takagi et al., 1965). [...]

It is well known both from experimental and clinical observations, that prolonged cortisone administration can result in the induction of de novo ulcera, exacerbation of latent ulcers or the reactivation of previously healed ulcers. The mechanism of this action is still unresolved. [...]

Extracts obtained from both animal and plant tissues have been shown to exert both 'in vivo' and 'in vitro' antihistamine-like activity. [...]

Since the introduction of foxglove in clinical medicine by Withering in the 18th century, extensive clinical and experimental investigations have been performed to elucidate the mechanism of action of cardiac glycosides. Until recently, it was believed that cardiac glycosides exert fundamentally different actions on normal and failing myocardium. [...]

Clinical and experimental evidence suggests a link between elevated gastric secretion and peptic, especially duodenal ulcer. While a high secretion of acid and pepsin by the gastric glands may not necessarily be the sole cause of peptic ulcer, there are certain conditions in which there seems to be a significant correlation between gastric acidity and incidence of peptic ulcer. [...]

In 1856, Vulpian described the formation of a green colour when the adrenal medulla was moistened with ferric chloride; iodine produced a red coloration. The medulla was shown to develop a blue colour with ferric sulphate (Colin, 1856), while the formation of a brown colour on adding dichromate to adrenal extracts was described by Menle in 1865. These observations laid the foundation for subsequent attempts to estimate adrenaline by chemical means. Following the isolation of the physiologically active principle of the adrenal medulla, by Takamine and by Aldrich (1901), attempts were made to utilise various colour reactions for the estimation of adrenaline in medullary extracts.

It is now well established that atheroscleretic-like chances can be demonstrated histologically in rabbits following prolonged feeding with cholesterol added to the diet. Thus, it has been reported by Rinzler et al. (1956), that, as early as two and a half months following administration of a diet containing 2 per cent cholesterol and 6 per cent corn oil to rabbits, histological lesions are detectable in the walls of the aorta. [...]

The exact physiological significance of the frequent occurrence of adrenaline and noradrenaline in varying ratios in different body tissues is still unknown. The earliest pharmacological distinction between the actions of the two agents, was based upon the well-known observation that after a previous injection of the ergot alkaloids, the pressor response to adrenaline is usually inverted, while that to noradrenaline although diminished is not reversed. [...]

Coronary insufficiency occurs when there is a disproportion between the oxygen needs of the heart and the oxygen supply to the heart. It can therefore be produced either (a) by decreasing the available oxygen supply to the heart, (b) by increasing the work of the heart, or (c) by a combination of both changes. The diagnosis of angina pectoris or coronary insufficiency can often easily be made in the presence of a typical clinical history and characteristic electrocardiographic changes. In many instances, however, the appraisal of substernal and precordial pain may be extremely difficult.

The production of bioactive lipids by phospholipases has long been appreciated as an important mode of cellular communication. Phospholipase D (PLD) enzymes hydrolyze phosphatidylcholine to generate a choline headgroup and the important lipid second messenger, phosphatidic acid (PtdOH). PLD family members are found in a diverse range of species from viruses to humans and regulate many important physiological processes including cytoskeletal rearrangements, cell migration, immune response, and cell proliferation. As such, PLD promotes oncogenic processes and elevated PLD activity has been documented in many types of cancerous tissue and derived cell lines. PLD activity is associated with cell cycle progression, resistance to apoptotic stimuli, and tumor cell invasion, but the molecular mechanisms of these PLD-mediated processes are largely uncharacterized. The goal of this project was to identify and characterize novel PLD-protein complexes in order to further understand the mechanisms by which PLD promotes cancer growth and survival. In this dissertation, PLD-derived PtdOH is demonstrated to be a novel regulator of pro-survival Akt kinase in glioblastoma cells by regulating membrane recruitment and activation of Akt. Inhibition of PLD enzymatic activity and subsequent Akt activation decreases GBM cell viability by specifically inhibiting autophagic flux. Additionally, PLD is shown to interact with a number of metabolic enzymes and a potential role for the regulation of cellular bioenergetics in GBM is explored. The results of this research provide mechanistic insight into PLD-mediated cancer cell survival.