The effect of oral contraceptives on the urinary excretion of several methionine metabolites was determined in women before and after they had received a 3-g dose of L-methionine. Nine women between the ages of 20-29 years served as subjects: five had been using a combination-type oral contraceptive for six months or more (experimental group), and four had not been using these drugs (control group). Cystathionine excretion by both groups before and after the methionine loading was in the range reported for normal female subjects who were not deficient in vitamin B₆ (Krishnaswamy, 1972; Shin and Linkswiler, 1974). Changes in urinary methionine metabolites that were apparently produced by oral contraceptive drugs are: (1) homocysteine was detected in the basal urine of three of the oral contraceptive users. After methionine loading, it was found in the urine of four of these subjects, two of whom excreted measurable quantities. In contrast, three of the control subjects excreted traces of homocysteine only after methionine loading. (2) The mean excretion of taurine by oral contraceptive users was only one-tenth of that excreted by the control subjects. The activity of erythrocyte glutamic oxaloacetic transaminase (EGOT) before and after in vitro stimulation with added pyridoxal phosphate was similar in both groups. Basal activity of erythrocyte glutamic pyruvic transaminase (EGPT) was lower in oral contraceptive users, although the mean values for both groups were within the normal range reported by Miller et al. (1975) and Woodring and Storvick (1970). The percent in vitro stimulation after addition of pyridoxal phosphate was somewhat higher in oral contraceptive users, but the difference was not statistically significant. Thirteen free acidic and neutral amino acids (including metabolites of the methionine pathway) were measured in the urine specimens. The sum of the urinary excretion of these 13 amino acids was significantly lower (p < 0.01) for oral contraceptive users than for control subjects. However, total α-amino nitrogen excretion, measured in the same urine specimens, was similar for both groups. / Graduation date: 1976

The effect of oral contraceptives on urinary and plasma vitamin B₆ as well as erythrocyte transaminase activities was investigated in women. Five women who were taking oral contraceptives and four who were not using these drugs served as subjects. They were apparently healthy and free from any known metabolic disorder. The subjects, who consumed normal diets, recorded their dietary intake for three days. Twenty-four hour urine specimens were collected on two consecutive days by the subjects. On the morning of the second day blood for the various biochemical measurements was drawn from fasting subjects. Following the blood drawing the women were given an oral dose of 3 g of L-methionine. Results of the methionine load test are reported elsewhere. The subjects consumed diets that supplied at least two-thirds or more of their National Academy of Science-National Research Council (1974) Recommended Dietary Allowances (RDA) for most nutrients except iron and vitamin B₆. The mean dietary intake of vitamin B₆ was 1.57 mg per day for the untreated women and 1.52 for the oral contraceptive users. On both days the mean levels of free and total vitamin B₆ in urine were less in the oral contraceptive users than that in the untreated controls, but the differences were not statistically significant. There appeared to be some relationship between dietary intake of vitamin B₆ and urinary excretion of the vitamin. The methionine loading dose did not affect the excretion of vitamin B₆ The mean plasma level of vitamin B₆ was lower for the oral contraceptive users than for the untreated controls although the difference is not statistically significant. There was, however, a large variation in values among the subjects taking oral contraceptives. Two of them had extremely low plasma vitamin B₆ levels. Vitamin B₆ in the plasma did not appear to be related to dietary intake or urinary excretion of the vitamin. Erythrocyte glutamic oxaloacetic transaminase (EGOT) and erythrocyte glutamic pyruvic transaminase (EGPT) activities with and without in vitro stimulation with pyridoxal phosphate (PALPO) were also measured. There were no significant differences between the two groups in EGOT and EGPT activities with and without in vitro stimulation. According to the activity indexes (PALPO stimulated activity/activity without added PALPO) for EGOT and EGPT (Sauberlich et al., 1972), all subjects had adequate vitamin B₆ nutritional status. Activity indexes for EGOT and EGPT did not appear to be related to urinary or plasma levels of vitamin B₆ Urinary and plasma vitamin B₆ levels and erythrocyte trans- aminase activities were not related to the length of time the women had been taking oral contraceptives or the estrogen content of their oral contraceptive agent. / Graduation date: 1976

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No description available.

This research initiated an investigation of the structural relationships between melanocyte stimulating hormone (α-MSH) and its melanin dispersion on lizard (Anolis carolinensis) and frog (Rana pipiens) skins bioassays as representing models for mammalian and amphibian melanocytes, respectively. From previous extensive structure-activity relationships of α -MSH together with the theoretical modeling we were able to design a group of linear and cyclic peptides related to "4-10" fragment analogues of α -MSH. The solid phase synthesis of α -MSH and its related analogues using the p-methyl-benzhydrylamine resin was accomplished. The C-terminal carboxamide and N-terminal acetylamide were maintained in all peptides synthesized. The cyclic peptides were prepared in solution phase using the linear peptides generated by solid phase. All the cyclization were done by using the hydrochloride salts of the peptide and DMF as solvent with diphenylphosphoryl azide (DPPA) as a coupling reagent in the presence of K₂HPO₄ as a base. The yields of the cyclic peptides were in the range of 30-40 percent. In all the synthesized peptides the replacement of D-Phe⁷ with L-Phe⁷ causes reduction in the potency of the peptide on lizard or frog skins bioassays. Also, the reduction or increase in ring size in the cyclic peptide from a 23 membered ring diminishes the biological effect of the peptide under testing.

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No description available.

Chemotherapy and radiotherapy are widely accepted as common forms of treatment for cancers. The majority of cancer patients receive chemotherapy alone or in combination with radiotherapy. Most chemotherapeutic drugs cause DNA damage to the rapidly dividing cancer cells but normal cells are also damaged in the process. Therefore DNA repair levels in tumour and normal cells may determine the success of the treatment. The aim of this work was to evaluate the use of DNA repair biomarkers for assessing responses to chemotherapeutic drugs. The novel technique of imaging flow cytometry was employed to analyse the induction and resolution of γ-H2AX and RAD51 DNA repair biomarkers in DNA repair normal cell lines MRC5-SV1 and NB1-HTERT, an ATM-deficient cell line AT5BIVA (derived from an Ataxia Telangiectasia patient) and an XPF-deficient cell line GM08437B. Two cell lines were also developed, MRC5-SV1R and NB1-HTERTR which had been made resistant to HN2. A range of chemotherapeutic drugs, Adriamycin, Cisplatin and Nitrogen Mustard which have different modes of action were examined in this work. We have demonstrated distinct differences in γ-H2AX and RAD51 foci induction and resolution between the two DNA repair normal cell lines following exposure to different chemotherapeutic drugs. Additionally, it was demonstrated that both the resistant and sensitive cell lines have elevated γ-H2AX and RAD51 expression profiles in comparison to the parental cell lines over a 48 hour period post treatment with the cross-linking agent HN2. It is concluded that while both the γ-H2AX and Rad51 biomarkers may be useful for determining chemotherapeutic response, a larger cohort of cell lines and tumour samples is required for further analysis.

No description available.