published_or_final_version / Dentistry / Master / Master of Dental Surgery

published_or_final_version / Speech and Hearing Sciences / Doctoral / Doctor of Philosophy

The objective of this research was to indirectly determine the existence of a possible retinal-endocrine pathway activated, or Inhibited, by artificial fluorescent light as evidenced by it subsequent effects on bone metabolism. Forty-eight male Long-Evans post-breeder rats, half of which were bilaterally orbitally enucleated, were used in this experiment. A 21-day pretreatment diet contained calcium and phosphorus, each at a level of 0.2% of the diet, with no dietary vitamin D. During the last seven days of this period the animals were in complete darkness. For the 12-week experimental period, the diet contained 0.6% calcium and 0.4% phosphorus, and oholecalciferol wets administered the first day by intubation. During this time, four groups of 12 animals each, half of which were bilaterally orbitally enucleated, were exposed to either ultraviolet lights, cool green lights, Vita-Lite (full spectrum) lamps, or kept in complete darkness in specially constructed environmental boxes. On the first and last day of the experimental period, the left femurs were x-rayed and blood was sampled. The serum of the animals was analyzed for alkaline phosphatase, total calcium and total phosphorus. Bone density was determined. Femur ash was measured for total calcium and total phosphorus. Under all lighting conditions, for both the sighted and enucleated rats, the parameters measured in the serum declined. For serum alkaline phosphatase, the sighted rats under the cool green lights had the least change; the sighted in darkness had the greatest decline. The least change in serum total calcium occurred for both the sighted and enucleated rats under the cool green lights, whereas the greatest decline was for the sighted rats under the Vita-Lite lamps and the enucleated under ultraviolet lights. The sighted rats under the cool green lights had the highest percent ash per gram of dry fat-free weight; the sighted under the Vita-Lite lamps had the lowest. The highest ash calcium was in the sighted rats under the cool green and the Vita-Lite lamps. By both methods of bone density measurements, specific gravity and densitometry, the sighted rats under the cool green lights had the greatest loss. Overall there appeared to be more significant differences among the sighted animals for the various lighting conditions than for the enucleated. Also the enucleated rats had less extreme variations from the mean than the sighted. The results of this study suggest that the light mediated by the pbotoreceptors of the retina of the sighted rats produced an effect on bone metabolism. / Graduation date: 1982

The present study sought to define a possible role of phosphorus-stimulated ammoniagenesis, previously observed in vitro and in experimental animals, in the hypocalciuric effect of phosphorus in young men. It was hypothesized that titrating some of the hydrogen ions destined for excretion with ammonia would be beneficial to kidney calcium reabsorption because ammonium ion unlike hydrogen ion does not increase urinary calcium loss. To test this hypothesis, seven young men (22 - 31 years old and average weight of 70 kg) were fed a single menu providing 800 mg phosphorus, 1200 mg calcium, 11.7 MJ (~ 2800 kcal) and 14.5 g nitrogen for 10 days. In a subsequent 10-day period, dietary phosphorus was doubled to 1600 mg by the addition of cheddar cheese and milk to the menu. Dietary nitrogen, calcium and vitamin D were equalized for the two periods. Three 24-hour urine samples and a fasting blood sample were collected at the end of each experimental period. Comparison of period 2 with 1 showed urinary phosphorus excretion + 82%, urinary calcium excretion - 38%, serum phosphorus + 6.2%, serum calcium - 3.8%, urinary sulfate and creatinine excretion no change. Urinary ammonia nitrogen excretion increased in all seven subjects with an average increase of 13%. Furthermore each individual increase in ammonia nitrogen excretion was found to be directly correlated with urinary phosphorus excretion (r = 0.76, P < 0.05). Urinary urea nitrogen excretion was found to vary inversely with urinary ammonia nitrogen excretion with an average decrease of 12% and urinary total nitrogen excretion decreased 14% for the entire group. Results obtained therefore offer a mechanism by which phosphorus directly improves the non-parathyroid hormone portion of tubular calcium reabsorption. The magnitude of the effects seen however suggest that phosphorus-stimulated ammoniagenesis only plays a small role in the mechanism of the hypocalciuric effect of phosphorus in young men. / Graduation date: 1996

This study was designed to evaluate the effect of glucose on plasma pyridoxal 5'- phosphate (PLP) concentration. The objective was to determine whether there was a negative relationship between glucose ingestion and plasma PLP concentration and to evaluate the possible mechanism of decreased PLP after acute glucose ingestion. Seven healthy subjects (three males and four females) completed the oral glucose tolerance test (OGTT) on three separate occasions over a period of three weeks. Each week, subjects ingested the assigned solutions (a water solution with artificial sweetener equivalent to 25g glucose, a 25g glucose or a 75g glucose load) in a randomized order. Plasma PLP, pyridoxal (PL), 4-pyridoxic acid (4-PA), pyridoxine (PN), glucose, insulin, alkaline phosphatase (AP) activity and red blood cell PLP concentrations were measured at 0 (fasting) (TO), 1 (T1), 2 (T2) and 3 (T3) hours. The mean vitamin B-6 intake based on two 3-day dietary records was 1.57 ± 0.34 mg/day. All subjects had normal glucose tolerance. There were gender differences among the three solutions. Both the water solution and the 75g glucose load showed a significant decrease in the mean plasma PLP concentration was observed at T3 for males and at T2 for females (p<0.05). An overall mean decrease of 20% (9nmol/L) and 15% (7 nmol/L) was observed for males and females, respectively, after the 75g glucose load. The 25g glucose load resulted in a lower decrease in the mean plasma PLP concentration at each time point compared with the 75g glucose load, but no significant difference was found in the level of decrease between the two glucose loads. Both genders had a non-significant increase in the mean plasma PL and PN concentrations for the three solutions. Mean plasma 4-PA concentration was decreased at T1 with the three solutions. There was no significant change in the plasma AP activity at any time points after the three solutions. In addition, no significant increase in mean red blood cell PLP concentration was observed at all time points after the three solutions. This study found a negative relationship between glucose ingestion and plasma PLP concentration. However, it did not provide clear evidence for the hypothesized mechanism of the decreased plasma PLP concentration after acute glucose load. Further studies are required to determine the mechanism by which glucose decreases plasma PLP concentration. / Graduation date: 2000

This research was designed to study the perinatal and postweaning effects of the interaction between ethanol and low dietary zinc during gestation and lactation in the rat. Pregnant rats were fed liquid diets containing either 2 or 10 μg zinc/ml with or without 30% of kcal from ethanol throughout gestation and lactation. The liquid diet formulation was nutritionally adequate to insure offspring growth and survival during lactation. At weaning, dams and five of eight offspring from each litter were killed by exsanguination under sodium pentobarbital anesthesia. The remaining offspring were orally inoculated with Streptococcus mutans and fed a caries-promoting diet for six weeks. The low zinc diet produced a moderate zinc deficiency in dams as evidenced by a decrease in tissue zinc content, serum alkaline phosphatase activity, and urinary zinc concentration. Despite the presence of high zinc content in the diet, ethanol antagonized maternal zinc status to a level typical of that produced by the low zinc diet. The lowest zinc status, however, was found when low dietary zinc and ethanol were combined. The maternal interaction between ethanol and zinc also depressed offspring serum zinc and alkaline phosphatase activity in a similar manner but the magnitude was smaller. The maintenance of a lower than normal maternal tissue zinc and decreased maternal urinary excretion of zinc suggested a maternal attempt to support the growth and development of offspring despite zinc deficiency. Physiological consequences of ethanol-antagonized zinc status were evidenced by depressed activity of maternal and offspring serum alkaline phosphatase, increased maternal urinary excretion of hydroxyproline, decreased offspring molar enamel and dentin zinc content, increased dental caries score, and decreased cross-linking structure of mandibular second molar enamel. The liquid diet developed in the present study was nutritionally adequate and allowed for the investigation of a single nutrient deficiency, zinc, in ethanol fed rats during gestation and lactation without confounding effects of general malnutrition. Although the direction of interaction was predominately an effect of ethanol on zinc rather than the effect of zinc on ethanol, this study clearly indicates that zinc deficiency is an important consequence of maternal ethanol ingestion. / Graduation date: 1984

Taurine (2-aminoethane sulfonic acid) is one of the most abundant inhibitory amino acids in the mammalian central nervous system (CNS). Substantial evidence exists to suggest that this amino acid is a physiological modulator of neuronal excitability. Taurine is also a potent anticonvulsant in a variety of animal epilepsies and in certain human epileptics. The mechanisms of these neuromodulatory and anticonvulsant actions of taurine are not known. I have investigated a proposed relationship between altered amino acid metabolism, seizure-susceptibility and the anticonvulsant action of taurine. The findings of the work presented in this dissertation indicate that in the genetically seizure-susceptible rat there are alterations in the subcellular concentration and transport of taurine. Furthermore, the data presented here indicate that these alterations in the CNS handling of taurine are not a consequence of seizure activity but rather may be contributing to the seizure-susceptibility. This supports the hypothesis that taurine is a physiological modulator of neuronal excitability and that defects in this neuromodulatory process may contribute to seizure-susceptibility. The action of taurine was found to not be mediated by a redistribution of glutamate in the brain but instead may be by increasing the conversion of glutamate to GABA.

Glycoproteins play a key role in cellular growth and differentiation. In order to study glycoprotein biosynthesis and processing, we have chosen the murine Immunoglobulin M (IgM) system as a model. Our system utilizes hybridoma, lymphoma and plasmacytoma cell lines which synthesize intracellular, membrane-bound and secreted IgM. Each type of IgM is synthesized during a specific phase of B-cell differentiation. We have examined the kinetics of IgM synthesis and processing in cells at each developmental stage. The rate of synthesis of membrane-bound and soluble IgM are different. Characteristic rates for membrane versus soluble IgM may be dependent on the extent of oligosaccharide processing. The membrane-bound IgM contains more high-mannose oligosaccharide than does the secreted product. In addition, we have begun to determine how protein structural requirements can affect final glycosylation patterns on the glycoprotein. Two cell lines were studied which secreted smaller than normal IgM heavy chains in tissue culture. One cell line studied (208) contains one glycosylation site, while another (562) retains three sites on the molecule synthesized in tissue culture. Studies performed on these cell lines in tissue culture indicate greater processing of the oligosaccharides on these mutant IgM molecules when compared to the parental cell line (PC700). Studies on the 208 IgM molecules synthesized in the mouse and purified from ascites fluid confirm these results. Upon injection into the mouse, the 562 cell line reverts to produce protein and carbohydrate structures characteristic of the parental cell line. Studies on the 562 protein purified from ascites fluid illustrate the need for more precisely defined cell lines and genetic engineering for the study of altered protein structures.

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