The development of a radioimmunoassay for salmon calcitonin is described. Synthetic salmon calcitonin was iodinated with I(125) and used as tracer. The coated charcoal method, suitably modified, was employed to separate bound and free salmon calcitonin. Antisera were raised by intradermal and intramuscular injection of calcitonin conjugated to keyhole limpet hemocyanin with carbodiimide. The sensitivity of the assay is 50 - 60 pg/ml of incubate. The disappearance of synthetic salmon calcitonin in rainbow trout was determined, illustrating two components, an initial rapid decline followed by a prolonged drop in concentration. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Acid extracts of the ultimobranchial glands of domestic fowl Gallus domestica and the dogfish Squalus suckleyi had a very potent hypocalcemic effect when injected into young rats, while extracts of the corresponding thyroid glands were devoid of such activity. The log. dose response paralleled that obtained with mammalian calcitonin preparations. The data indicate that the ultimobranchial gland, rather than the thyroid, is the source of calcitonin in these species. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Thesis (Ph.D.)-- University of Adelaide, Dept. of Orthopaedics and Trauma, 2000. / Bibliography: leaves 141-169.

Although the first preparations of the hypocalcemic hormone, calcitonin (ct), were extracted from rat thyroid glands, histological evidence showed that the "c" cells which produce the hormone are not restricted to this gland, but also occur in the parathyroid and thymus tissues of mammals. These cells arise embryologically from the last branchial pouch and in non-mammals they form a separate ultimobranchial gland which also contains hypocalcemic activity. The work described in this thesis provides evidence that this activity results from polypeptides structurally similar to those isolateo from mammalian thyroid tissues and.explores the relationship between the structural and functional differences of the two types of ct. A survey of four mammalian thyroid tissues (human, bovine, porcine and murine) ano four non-mammalian ultimo-branchial tissues (turkey, chicken, salmon and dogfish) demonstrated that these tissues contained hypocalcemic polypeptides with molecular weights of about 4000 as determined by gel filtration. When extracts were prepared using an organic solvent mixture developed for the thyroid ct' s the ultimobranchial tissues yielded more hypocalcemic activity on a fresh weight basis and the final product had a higher specific activity. Salmon ultimobranchal tissue was collected on a large scale and extracted to provide material for chemical characterization. A series of three gel filtration stages on sephaoex g-50 alternating with two ion-exchange chromatography stages on se-sephadex c-25 at two ph's provided a 300,000 fold purification and yielded 15 mg of pure salmon ct. amino acid analysis and partial characterization of tryptic peptides indicated that the ultimobranchial hormone was a 32 amino acio polypeptide with a disulfide bridge at the c-terminus. Although these features are also common to all the mammalian ct's, there are a number of unique features in the salmon ct structure. These structural differences were also reflected in the biological activity of the hormone. Salmon ct was nearly 50 times more active than human ct in the standard bioassay and the response to the salmon hormone was prolonged. Tests in plasma both in vivo and in vitro indicated that salmon ct was much more stable than the 'thyroid ct' s suggesting a possible reason for its greater potency. A survey of cohn fractions from human plasma showed that fractions iii-o, iv-1 iv-4 contained enzymes capable of rapidly degrading porcine ct. in further studies on fraction iv—1 a selective "calci-toninase" was purified by chromatography on deae-sephadex, sephadex g-200 and cm-sephadex. this enzyme rapidly inactivated porcine ct, but had no significant effect on salmon or human ct. synthetic porcine ct was digested with the enzyme and the resultant peptides were isolateo and identified. The nature of these peptides indicated that the enzyme was a peptidase with a specificity for the carboxyl side of arginine residues. similar digestions of pure native salmon ct produced no peptides providing at least a partial explanation for the greater stability of this hormone. These experiments also showed that the enzyme would not split at all arginine residues and would not cleave bonds associated with other basic residues. The data indicated that the enzyme had a molecular weight of about 30,000 and probably was derived from a precursor with a molecular weight of about 100,000. Tests of the action of the enzyme on fibrinogen showed that it was not thrombin. comparison of available data with that for other plasma enzymes indicated similarities to the kallikrein family of enzymes, but the "calcitoninase" does not appear to be identical with any of the well studies members of this group. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Human calcitonin (hCT) is a peptide hormone that is produced by the thyroid gland where it regulates blood calcium and stimulates bone formation. However, increased concentrations can cause hCT to aggregate into amyloid fibrils where they can cause cellular toxicity. In this dissertation, we investigated the role of the N-terminal intramolecular disulfide bond, the effects cholesterol derivatives, the inhibitory effects of a group of polyphenolic molecules, and membrane interactions on hCT amyloid formation. To better understand hCT amyloid formation, we investigated the role of the N-terminal intramolecular disulfide bond has on the aggregation kinetics of hCT. Our results demonstrated that the presence of the disulfide bond is key to the formation of the oligomeric nucleus that is needed for amyloid formation. We also investigated the role of cholesterol, cholesterol sulfate, and 3β-[N-(dimethylaminoethane)carbamoyl]-cholesterol (DC-cholesterol) in moderating hCT fibril formation. We showed that cholesterol does not significantly affect hCT fibrillization while high concentrations of cholesterol sulfate has a moderate inhibiting effect. However, DC-cholesterol strongly inhibits hCT fibril formation in a concentration-dependent manner suggesting the role of electrostatic and hydrogen bonding interactions have in moderating the interactivity between hCT and the surface of DC-cholesterol vesicles. We also probed the inhibitory effects of a group of polyphenolic molecules on hCT fibril formation. Our results showed that molecules containing vicinal hydroxyl groups on the phenyl ring effectively inhibits hCT fibril formation though a plausible covalent linkage between the oxidized polyphenol and hCT. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

Thesis (M.Sc.)--Memorial University of Newfoundland, 2002. / Bibliography: leaves 104-111.

No description available.

Der spezifischste und sensitivste biochemische Tumormarker in der Diagnostik und Verlaufskontrolle des MTC ist Kalzitonin. Der hCT-Spiegel sollte nach totaler Thyreoidektomie nicht mehr messbar sein. Ein messbares hCT weist nach Therapie auf ein Rezidiv oder eine Metastasierung hin. Die hCT-Sekretion kann durch Gastrin stimuliert werden, was beim Pentagastrin-Stimulationstest genutzt wird. Im Rahmen dieser Arbeit wurde untersucht, welchen Stellenwert die Bestimmung des basalen Kalzitonin im Vergleich zum Pentagastrin-stimulierten hCT in der Nachsorge des MTC einnimmt. Hierzu wurden 129 Pentagastrintests von MTC-Patienten der Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg retrospektiv ausgewertet. Bei sechs Prozent der Patienten fand sich nach anfänglicher biochemischer Remission ein hCT-Anstieg. Die im Pentagastrintest stimulierten hCT-Werte zeigten den Anstieg früher an als die lediglich basal gemessenen Werte. Das Ergebnis dieser Arbeit lässt den Schluss zu, dass der Pentagastrintest weiterhin ein wichtiger Bestandteil in der Nachsorge von Patienten mit MTC ist, da die stimulierten hCT-Werte im Einzelfall eine noch subklinische residuelle Erkrankung, Metastasierung oder ein Rezidiv frühzeitig detektieren. / Calcitonin is the most specific and most sensitive biochemical marker in diagnostic investigation and follow up of patients with medullary thyroid carcinoma. hCT-level should be incapable of measurement after complete thyroidectomie. A measurable hCT after therapy indicates recrudescence or metastases. hCT-secretion can be stimulated by gastrin, which is used in the pentagastrin-stimulationtest. In the context of this study the significance of basal calcitonin compared to pentagastrin-stimulated hCT in the after-care of patients with medullary thyroid carcinoma was analysed. Therefore 129 pentagastrin-tests of MTC-patients from the ´Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg´ were evaluated retrospectively. In a percentage of 6 an increase of hCT could be found after initial biochemical remission. The pentagastrin-stimulated hCT-values indicated the increase earlier than the basal values. To draw a conclusion the pentagastrin-stimulationtest remains an important component in the follow-up of patients with MTC because stimulated hCT-levels can - in individual cases - detect subclinical residual disease, metastases or recrudescence early.

No description available.

No description available.