Thesis (M.S.)--University of Wisconsin--Madison, 1965. / eContent provider-neutral record in process. Description based on print version record. Bibliography: l. 30-31.

Thesis (Ph. D.)--Columbia University, 1935. / Vita. Bibliography: p. [21].

Thesis (Ph. D.)--Columbia University, 1933. / Vita. Bibliography: p. [17].

Thesis (M.S.)--Bowling Green State University, 2008. / Document formatted into pages; contains ix, 65 p. : ill. Includes bibliographical references.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references. Also available in electronic version.

The plasma calcium level is one of the most precisely regulated constants of the internal environment, and the large reservoir of calcium in the skeleton is primarily responsible for this homeostasis. The experiments presented in this thesis were designed to study quantitatively the regulation of plasma calcium. Acute hypocalcemia was induced by continuous intravenous EDTA infusion (a calcium chelating agent) at a known rate, and hypercalcemia was induced by intravenous calcium gluconate infusion. The rate used in most cases was 10 mg. calcium per kg. for one hour. Both mobilization and storage of calcium appeared to depend on equilibrium with a labile calcium storage pool in bone. The rate of storage or mobilization was shown to be proportional to the amount of blood coming in contact with this labile pool in bone (bone blood flow), and the plasma/bone difference in Ca++ activity. Bone blood flow was measured using the Pick Principle for calcium storage, and it was calculated to be 6.46 ± 0.60% of the cardiac output (14 dogs). The extracellular fluid calcium was also estimated and found to be 15.73 ± 0.72 mg/kg (14 dogs), corresponding to an extracellular fluid volume of approximately 20% of body weight. Less than 5% of the injected calcium was excreted in the urine. The labile calcium storage pool in bone was estimated from the changes in the bone-blood equilibrium after calcium was injected, and was found to be 2 - 5 times greater than the extracellular calcium. The net loss of calcium from the plasma after calcium injection, which is assumed to equal the rate at which calcium is used for bone mineralization less calcium released by resorption, was estimated as 1 - 2 mg. Ca/kg/hr. or 0.15 - 0.35% of the total bone calcium per day. The methods described provide a means of assessing quantitatively the factors involved in acute regulation of the plasma calcium level. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Isotopic and spectrophotometric assays show that micromolar concentrations of heavy metal ions (particularly Ag⁺ and Hg²⁺) stimulate ATPase activity but inhibit Ca²⁺ uptake in isolated SR vesicles. Both effects are caused by increased Ca²⁺ permeability of the membrane, apparently the result of activation of the Ca²⁺ release system of the vesicles due to heavy metal binding to a critical sulfhydryl group associated with the Ca²⁺ release channels. CU²⁺catalyzed co-oxidation of this sulfhydryl with exogenous cysteine to form a mixed disulfide also results in activation of the Ca²⁺ release system. The rate and extent of Cu²⁺/cysteine-induced release is maximal at physiological pH and is inhibited by local anaesthetics and Mg²⁺, suggesting that the redox state of this sulfhydryl may play a role in activation of the Ca²⁺ release system of intact muscle. Modification of the SR with the proteolytic enzyme trypsin also increases the Ca²⁺ permeability of the SR, and enhances the rate of Ca²⁺ release activated by cAMP, doxorubicin, Hg²⁺, and Cu²⁺/cysteine. The rates of release activated by all reagents are stimulated by a factor of five after five minutes exposure to trypsin. Hg²⁺- and Cu²⁺/cysteine-activated release are not stimulated further, while cAMP- and doxorubicin-activated release continue to increase up to maximum of 20-fold stimulation after 15 minutes exposure to trypsin. Inhibitors of the Ca²⁺ release system such as Mg²⁺ and ruthenium red still inhibit release from proteolytically modified SR, and the binding affinities of activators and inhibitors to their sites are not significantly altered by proteolysis; only the rates of Ca²⁺ transport are affected. The most probable mechanisms of tryptic stimulation of Ca²⁺ release are (1) removal of a regulatory protein or subunit of the Ca²⁺ release system, making more channels available for transport; (2) increasing the single channel unitary conductance; (3) increasing the open time of activated channels. The biphasic character of proteolytic stimulation of cAMP- and doxorubicin-activated release (as opposed to monophasic stimulation of Hg²⁺- and Cu²⁺/cysteine-activated release} suggests that more than one of the above parameters are involved in tryptic stimulation of the Ca²⁺ release system.

No description available.

Call number: LD2668 .T4 1943 T3 / Master of Science