Thesis--M.D., University of Hong Kong, 1982.

Thesis (M. Phil.)--University of Hong Kong, 1978. / Typewritten.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Many studies in animals and humans have demonstrated that exposure topolychlorinated biphenyls (PCBs) can interfere with the normal function of the thyroid system. In this study, Atlantic croaker (Micropogonias undulatus) were exposed to a PCB mixture (Aroclor 1254) or one of three individual congeners (ortho-PCB 153, ortho-PCB 47 or planar PCB 77) in the diet for 30 days to investigate the effects of PCBs on thyroidal status. Thyroid hormones, thyroxine (T4) and triiodothyronine (T3) were extracted from plasma samples and measured with an enzyme-linked immunosorbent assay. Both male and female croaker exposed to the PCB mixture Aroclor 1254 (0.2 and 1.0 mg/kg body wt/day) had decreased plasma levels of total T3 when compared to the parallel control groups, but the effects on total T4 levels were inconsistent. Exposure to PCB 153 (0.1 and 1.0 mg/kg body wt /day) significantly lowered both T4 and T3, while PCB 47 at the same doses had no effect on thyroid hormone levels. Fish exposed to PCB 77 had no effect on T4 or T3 levels except an increase in T4 levels at the highest dose employed (0.1 mg/kg body weight/day). However, this dose of PCB 77 caused partial loss of appetite and may be too high to be relevant for the effects observed after exposure to Aroclor 1254 considering the fact that it constitutes only 0.31% of the PCB mixture. The results of the present study demonstrate that exposure to synthetic endocrine disrupting chemicals, such as PCBs at the higher end of environmentally realistic concentrations can have profound effects on the thyroidal status of Atlantic croaker. The ability of Aroclor 1254, as well as ortho-PCB 153, to consistently disrupt the natural homeostasis of the thyroid system in croaker is an important finding that contributes to a better understanding of PCB endocrine toxicity in teleosts.

published_or_final_version / Zoology / Master / Master of Philosophy

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Ο καρκίνος του θυρεοειδούς αδένα είναι ο πιο συχνός κακοήθης όγκος του ενδοκρινικού συστήματος και αποτελεί περίπου το 1% όλων των περιπτώσεων καρκίνου που διαγιγνώσκονται για πρώτη φορά. Θεωρείται υπεύθυνος για την πλειονότητα των θανάτων από ενδοκρινικό καρκίνο κάθε χρόνο. Περίπου 30.000 νέες περιπτώσεις κακοήθων θυρεοειδικών νεοπλασιών διαγιγνώσκονται ανά έτος και η επίπτωση αυξάνεται κατά 5-6 % κάθε χρόνο στις Η.Π.Α. Σύμφωνα με πρόσφατη μελέτη ο θυρεοειδικός καρκίνος υπερδιπλασιάστηκε τα τελευταία 30 χρόνια στην Αμερική. Διάφοροι παράγοντες έχουν ενοχοποιηθεί για την ανάπτυξη του θυρεοειδικού όγκου. Ο καλύτερα μελετημένος αιτιολογικός παράγοντας είναι η ακτινοβολία. Προηγούμενες βλάβες του θυρεοειδούς όπως βρογχοκήλη ή καλοήθεις όζοι αποτελούν ισχυρούς παράγοντες κινδύνου για ανάπτυξη κακοήθειας. Έχουν επίσης αναφερθεί ότι σχετίζονται με τις κακοήθειες του θυρεοειδούς και αρκετοί παράγοντες που συσχετίζονται με την αναπαραγωγική δραστηριότητα των γυναικών, όπως αριθμός κυήσεων, θηλασμός, ηλικία εμμηναρχής, χρήση αντισυλληπτικών, διαιτητικοί παράγοντες, δίαιτα πλούσια ή πτωχή σε ιώδιο, κατανάλωση ζωικού λίπους, λαχανικών και οστρακοειδών όπως και ένας αριθμός ογκογονιδίων. Μέσα από την διπλωματική αυτή εργασία έγινε φανερό πως η έρευνα σχετικά με τους μοριακούς μηχανισμούς που εμπλέκονται στην παθογένεια του καρκινώματος του Θ.Α. συνεχίζεται με εντατικούς ρυθμούς. Δυο θεωρίες επικρατούν. Αυτή της πολυσταδιακής καρκινογένεσης (multi-step carcinogenesis) και η.fetal cell carcinogenesis. Φαίνεται πως σε κάθε ιστολογικό τύπο καρκίνου του θυρεοειδούς κυριαρχούν διαφορικές μοριακές ανωμαλίες που σχετίζονται με την εξέλιξη του φυσιολογικού σε καλοήθη, καλά διαφοροποιημένο και αναπλαστικό καρκίνο του αδένα. Ωστόσο, είναι σαφές πως υπάρχουν ακόμα πολλά αναπάντητα ερωτήματα σχετικά με τα μοριακά μονοπάτια που οδηγούν στην ανάπτυξη των θυρεοειδικών νεοπλασιών. Στόχος της μελέτης αυτής είναι να συνοψίσει τα σημαντικότερα δεδομένα που εμπλέκονται στην παθογένεια του θυρεοειδικού καρκινώματος και που θα αποτελέσουν πολύτιμο εργαλείο για την περαιτέρω επιστημονική έρευνα με απώτερο σκοπό την μελλοντική μοριακή θεραπευτική παρέμβαση. / -

No description available.

Wastewater reclamation and reuse is imperative in water-starved areas such as the southwestern United States. In the Tucson Active Management Area, a geographic region defined for the purpose of groundwater management, the total demand for water already exceeds the available water supply, which consists of renewable ground water and the regional entitlement to Central Arizona Project water. Thus, the regional demand cannot be satisfied without resorting to groundwater mining unless water is reclaimed for local beneficial use. Less certain are the acceptable uses for reclaimed water and the nature of use-dependent treatments or water quality requirements that will protect human and ecological health. Disruption of thyroid-mediated actions is among the possible risks from chronic exposure to environmental contaminants. Endocrine disrupting compounds are generally of greater concern in this context than other trace contaminants because of the very low concentrations at which hormones induce physiological responses. Accordingly, a sensitive nuclear-based bioassay system was developed in order to evaluate environmental samples. A luciferase-reporter construct and the human thyroid receptor β (TR-β) construct in the human hepatoma cell line (HepG2) and human medulloblastoma cells (TE671) was evaluated for sensitivity. The transfected cells were exposed to the thyroid hormone, T3, in order to establish a lower thyroid hormone detection limit for the new bioassay procedure. The assay was then applied to environmental samples containing organics concentrated from final effluent derived from a conventional secondary wastewater treatment plant. The effluent samples activated thyroid receptor-mediated transcription. Also in this study, a two-dimensional gel electrophoresis (2D-DIGE) was used as an in vitro bioassay to look for wastewater related alteration of cellular protein expression in the human breast cancer cell T47D. Steps in this bioassay include the one-dimensional separation of proteins by isoelectric focusing followed by orthogonal electrophoresis to isolate the proteins. The consistency of test response was examined for wastewater-dependent up- or down-regulation of protein expression. Some proteins that were upregulated were preliminarily identified via mass spectrometry. Here, the procedure is used to provide direct information regarding the probable effects of residual hormones in treated wastewater on the activities of human, estrogen-responsive cells in cell culture.

The competition between two molecules of similar polarity for adsorption sites on the stationary phase is discussed in light of rapid kinetics of adsorption and desorption, and of the effects of temperature, acetonitrile, surfactant (cyclohexylaminopropane sulfonic acid, CAPS) and salt concentrations on the retention of the thyroid hormones (3,5-diiodothyronine, T2; 3,3',5-triiodothyronine, T3 and thyroxine, T4). A three parameter equation relates the surfactant concentration and ionic strength to the retention of the hormones and is analyzed in terms of the Stern-Gouy-Chapman theory. A second order polynomial describes the temperature dependency and permits the evaluation of the enthalpy, entropy and heat capacity, demonstrating a reduction in the molecular motion of the analyte with increasing surfactant and acetonitrile concentrations. The equation parameters for linear or non-linear equations, using data sets with or without homogeneous variances, are evaluated using a Simplex optimization procedure that uses one of two proposed optimization criteria. The construction and operation of a computer based gradient programmer for HPLC is described. A surfactant mediated gradient elution with electrochemical detection is examined for the analysis of serum thyroid hormones.