Myosin heavy chain (MHC) isoforms in vertebrate striated muscles are encoded by a highly conserved multigene family. Seven sarcomeric MHCs are known to be expressed in cardiac and skeletal muscles of the rat. These isoforms show distinct patterns of tissue-specific expression which are hormonally and developmentally regulated. Thyroid hormone has been shown to regulate the expression of the ventricular isoforms by causing an accumulation of alpha-MHC and a repression of beta-MHC. Alterations in thyroid status have also been reported to affect MHC isoforms in skeletal muscles. The first part of this study describes the development of a dot-blot assay with which to measure the levels of the sarcomeric MHC mRNAs. This assay was utilized in part two of this dissertation to analyze the effects of thyroid hormone administration on the expression of MHC and actin mRNAs in ventricular muscle, as well as in representative fast and slow skeletal muscles of the hypothyroid rat. The results indicate that expression of all of the MHC genes is regulated by thyroid hormone in a highly complex, tissue specific manner. Also, thyroid hormone caused transient increases in the expression of cardiac actin mRNA in the ventricle, but no actin isoform transitions were observed in any muscle type. The third portion of this dissertation describes the development of a cultured cell system that has been used to analyze changes in MHC and alpha-actin gene expression in response to thyroid hormone in vitro. Cultured primary fetal cardiomyocytes were found to express only the cardiac MHC and actin isoforms. In addition, the alpha- and beta-MHC isoforms were found to be regulated by thyroid hormone in a similar manner to that observed in the intact rat ventricle. In the final portion of this study, the promoter region of the thyroid hormone inducible gene, alpha-MHC, was isolated and ligated to the bacterial chloramphenicol acetyltransferase gene. Chimeric genes were utilized in transfection studies and found to be thyroid hormone inducible. The results suggest that DNA sequences in the 5' flanking region of the alpha-MHC gene are sufficient to mediate hormone induction of the gene.

The central role of the mammalian heart in the circulation was recognised by Nei Chung when he wrote in his Third Book of the Yellow Emperor's Classic of Internal Medicine (2698 - 2598 B.C.): Treatise on the Five Viscera in Relation their part in Perfecting Life, "The Heart is in accord with the pulse. The complexion of a person shows when the heart is in a splendid condition. The heart rules over the kidneys. . . . . . . . The importance of assessing the functional state of the heart was realised even by the early Egyptian physicians in the 17th Century B.C. as described in the Ebers Papyrus:- "The begining of the physician, secret : knowledge of the heart's movements and knowledge of the heart. There are vessels from it to every limb. As to this, when any physician, any surgeon, or any exorcist applies the hands or his fingers to the head, to the back of the head, to the hands to the place of the stomach, to the arms or to the feet, then he examines the heart, because all his limbs possess its vessels, that is, the heart speaks out of the vessels of every limb".

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A cytochemical analysis was undertaken of C cells of thyroid glands obtained from sixteen young oogs and five human s t ill - b o r n neonates. Tissues were fixed in selective liquid fixatives (N e lly 's , Carnoy s, glutaraldehyde-picric-acetic acid, glutaraldehyde-potassium dichromatesodium sulphate and formol-saline) or fixed in formalin vapour a f t e r freeze drying. Cryostat sections and some of the above fixatives were used for enzyme demonstration. Simple and conjugated proteins in the cytoplasm of canine C cells were studied by numerous cytochemical reactions. Acetylatiun, methylation, benzoylation, nitrosation, acid hydrolysis and aldehyde blockade as well as enzyme hydrolysis were employed to evaluate the aldehyde fuchsin, colloidal iron, toluidine blue and periodic acid-Schiff staining reactions in canine C cells. I have confirmed that the cytoplasm of canine C cells contains an abundance of acidic protein groups which are due to side-chain carboxyls. Mild acid hydrolysis, amongst other reactions, may result in peptide hydrolysis at the aspartyl group, which hydrolysis contributes to the anionic charge in the C cell cytoplasm. Basic proteins are not readily stained in the canine C c e l l . Bisulphide groups are numerous and their oxidation adds to the negative charge of the C cell cytoplasm. I found that the positive aldehyde fuchsin and colloidal iron reactions are not attributa ole to mucosubstances such as sulphomucms, sialomucins or acidic mucopolysaccharides, but seem to be imparted by an acidic protein unconjugated to polysaccharide. A positive aldehyde fuchsin reaction probably depends on both disulphidc and carboxyl groups within C c e lls . A positive colloidal iron reaction in canine C cells requires the presence of carboxyl groups but an increased number of these groups does not enhance the staining reaction. The conditions required generally for s ilv e r binding and more specifically for the Grimelius s ilv e r impregnation in canine C cells were evaluated by oxidation and various other cytochemical procecures. I found that the argyrophilia of thyroid C colls depends upon an exogenous reducing agent and upon pH, optimal impregnation occurring at a s lig h tly acid pH. Oxidation preceding s ilv e r impregnation by the Grimelius method, reduces the a f f i n i t y of structures in the cell for s ilv e r n itr a te . Indirect evidence supports the view that argyrophilia in the C cells depends upon disulphide groups. I t is suggested that s ilv e r nitrate and disulphide groups react in C cells to form silv e r nercaptide which produces the argyrophilia. The presence of C cel s was demonstrated in human neonates by means of cytochemical methods known to demonstrate C cells in dogs. C cells were found predominantly in the posterior region and upper pole of both lobes where they were found scattered in clusters of six to eight cells per high power f i e l d Two morphological forms of normal human C cells were observed - an ovoid cell and one with cytoplasmic processes. By demonstrating oxidative enzymes and masked metachromasia, three categories of e p ith e lia l cells have been shown in the neonatal thyroid gland : A ( f o l l i c u i a r ) , C and AC (intermediate) c e lls . The l a t t e r may be homologous with the oxyphil cells observed in normal and pathological adult thyroid glands. The c lin ic a l applications in which I have useo the results of the above studies are outlined in the la s t section of the dissertation.

by Poon Yim-chu Daisy. / Bibliography: leaves 128-148 / Thesis (M.Phil.) -- Chinese University of Hong Kong, 1983

by Lam Kang Yau. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 127-143). / Acknowledgements --- p.iii / Abstract --- p.iv / List of abbreviations --- p.vi / Introduction --- p.1 / Literature review / Chapter A. --- Historical background --- p.6 / Chapter B. --- Histology on the epidermis of squamate reptile --- p.8 / Chapter C. --- The effects of thyroid hormone on the integument in the vertebrate --- p.13 / Chapter D. --- Extrathyroidal conversion of T4 to T3 --- p.18 / Experiment 1. The study of epidermal cellular changes and the effect of Tx on the sloughing cycle of Elaphe taeniura / Introduction --- p.21 / Materials and methods --- p.22 / Results --- p.26 / Discussion --- p.34 / Experiment 2. To study the extrathyroidal conversion of T4 to T3 (5'-D activities) of Elaphe taeniura / Introduction --- p.47 / Materials and methods --- p.48 / Results --- p.52 / Discussion --- p.54 / Experiment 3. The study of the effects of T3 and Tx on the sloughing cycle of Elaphe taeniura and in vitro 5'-deiodinating activities / Introduction --- p.56 / Materials and methods --- p.58 / Resul ts --- p.63 / Discussion --- p.81 / Experiment 4. The study of plasma T3 and T4 levels during the sloughing cycle of Elaphe taeniura / Introduction --- p.111 / Materials and methods --- p.112 / Results --- p.114 / Discussion --- p.115 / General discussion --- p.120 / Summary and conclusions --- p.125 / References --- p.127

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