The symptoms, classification, occurrence and possible aetiologies of bipolar manic-depressive psychosis have been reviewed, with particular emphasis on the possible role of the vanadate ion (V5+) and cation transport in the illness. The effect of vanadate on cation transport in intact cells has been determined using the well-characterised HeLa cell line. Cation transport in virally transformed lymphoblastoid cell lines from 13 bipolar manic-depressive patients and 13 control subjects has been examined, under normal conditions and after treatment (24 hours) with lithium, ouabain or vanadate. The phosphatidylinositol system has also been examined in these cell lines, in view of the therapeutic effect of lithium, and its known inhibitory actions on inositol I-phosphatase. In HeLa cells, no effects of vanadate on cation transport were seen until concentrations greater than 3.2 x 10- 6 M. This was attributed to the intracellular reduction of V5+ to V4+ shown to occur using ESR. Similar decreases were seen in all the K+ influx pathways, with maximum decreases of approximately 30% at 10-4M vanadate extracellularly. Significant toxicity was also seen at these concentrations, with a maximum decrease in cell number of 40% at 10-4M vanadate. No change in the energy charge was seen and changes in ATP levels occurred subsequently to the changes in cell number, with a decrease of 40% at 10-4M vanadate. Using the lymphoblastoid cell lines, no significant differences were seen in any of the cation transport parameters examined, with the exception of mean sodium pump number which was 30% greater in the bipolar group compared with the control group. Lithium or vanadate treatment produced either no effect or inconsistent changes in cation transport. Ouabain treatment produced similar decreases in sodium pump number in both groups. Inositol uptake was similar in both groups, but the percentage incorporation into phosphoinositides was reduced in bipolar cell lines compared with controls.

Hen egg riboflavin binding protein (RfBP) acts as a source of riboflavin to the developing embryo. It is the most abundant vitamin binding protein in the egg white. Mutations giving rise to a lack of RfBP lead to embryo death at approximately 13 days. RfBP binds riboflavin tightly in a 1:1 ratio. On formation of this complex, the fluorescence of riboflavin is completely quenched; this quenching is thought to be due to the stacking of aromatic groups within the hydrophobic binding pocket. This quenching provides a convenient assay for the integrity of the riboflavin-binding site of the protein. RfBP consists of a single polypeptide chain of 219 amino acids of molecular mass 29.2 kDa. RfBP undergoes a number of post-translational modifications, namely: the formation of nine disulphide bonds, extensive glycosylation on Asn 36 and Asn 147, and the phosphorylation of eight serine side chains from between Ser 186 and Ser 197. The unfolding and refolding of RfBP was studied by denaturing in 6M guanidium chloride, followed by dilution in buffer, to start refolding. The processes were followed by both steady-state and stopped-flow circular dichroism and fluorescence spectroscopy. RfBP was found to readily unfold and refold, provided the disulphide bonds were intact. The regain of secondary structure was found to be too rapid to measure by the methods available (<12msec). The regain of tertiary structure was found to consist of 4 main phases, and a large proportion (80%) of the tertiary structure formed within 2 msec. The regain of riboflavin binding ability was complete at the end of the second phase, a reaction with a half-life of around 30 msec. In the presence and absence of riboflavin, the kinetics for the first 3 stages of tertiary structure changes seemed to be identical. In the presence of riboflavin, however, seemed to impede the completion of the final, very slow stage, with the refolding reaction only going to 95% completion. The dephosphorylation of the protein seemed to have no affect on this process. When the 9 disulphide bonds are reduced however, RfBP is unable to spontaneously reoxidise to a native-like state in the presence of an oxidised/reduced glutathione redox system. However, the addition of protein disulphide isomerase to the system increases significantly the yield of successfully reoxidised RfBP to about 50%. Attempts to prepare deglycosylated RfBP by chemical methods were unsuccessful since the treatment led to fragmentation of the polypeptide chain.

Graduation date: 1945

Thesis (Ph. D.)--Columbia University, 1945. / Vita. "Literature cited": p. 66-67.

Thesis (Ph. D.)--Columbia University, 1932. / Vita. eContent provider-neutral record in process. Description based on print version record. Bibliography: p. [21].

Thesis (Ph. D.)--Columbia University, 1945. / Vita. "Literature cited": p. 66-67.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xviii, 167 p.; also includes graphics (some col.) Includes bibliographical references (p. 115-121). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Wisconsin--Madison, 1939. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (2 leaves between numbered leaves 48 and 49).

Thesis (M.S.)--University of Wisconsin--Madison, 1947. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 26-29).

Thesis--Copenhagen. / "Litteraturfortegnelse": p. [144]-149.