http://adhlui.com.ui.edu.ng/jspui/handle/123456789/64 Theses in Medicine 2026-02-28T11:25:48Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/785 Title: EPIDERMAL GROWTH FACTOR IN MAN AND MOUSE: PHYSIOLOGICAL, CLINICAL AND EXPERIMENTAL STUDIES Authors: DAGOGO-JACK, S. E. Abstract: Epidermal growth factor (EGF), which was first isolated from the mouse submaxillary gland and later from human urine belongs to a new class of polypeptides collectively known as growth factors. These growth factors regulate cell growth, tissue differentiatIon and maturation. EGF has interesting interactions with the endocrine system particularly in the thyroid gland, where it stimulates proliferation and inhibits differentiated thyrocyte function in vitro. The synthesis of EGF in mouse submaxillary gland is, in turn, regulated by hormones such as thyroxine and testosterone. Ever since its discovery, attempts have been made to assign a role to EGF in normal physiology or in the causation of disease. The results have so far proved inconclusive. The aim of the present study was to investigate the significance of EGF in man and mouse by using radioligand binding assays to measure EGF levels in a number of physiological, clinical and experimental situations. Specific and sensitive radio immunoassays and radioreceptor assays were developed for both human and mouse EGF. Methodologies for the extraction of EGF from human and mouse tissues were validated. The human (h) EGF radioimmunoassay was optimised for use in saliva, urine and thyroid tissue homogenates and applied to populations of healthy subjects and patients with various diseases. The concentration of (m) EGF in homogenates from mouse thyroid and other tissues was measured by the homologous mEGF radioimmunoassay. The biological activities of both hEGF and mEGF detected by the radioimmunoassays were assessed in separate radio receptor assays and their molecular integrity, by gel chromatography. The main findings in this work were as follows: hEGF was found to be normally present in saliva of healthy subjects from the different racial groups without significant racial variations. The mean salivary hEGF concentration (pmol) was 368.55 ± 30.00 in Pakistanis, 457.25 ± 54.21 in Black Africans, 414.00 ± 31.20 in Chinese and 450.00 ± 58.22 in white Britons, p > 0.05. The mean salivary hF concentration in 27 pregnant famales and 23 healthy age - matched controls were similar (713.19 ± 56.10 vs 665.22±51.66 pmol/1); there was no correlation between salivary hEGF and gestational age among the former. Significant increases in salivary hEGF levels were observed In patients with goitrous thyrotoxicosis and in those with terminal renal failure. Declining urinary excretion of hEGF was observed in diabetic patients with worsening proteinuria. hEGF was found measurable in every human thyroid gland examined and increased concentrations were found in glands from patients with uncorrected thyrotoxicosis. Studies using immunochemistry localized hEGF to the cytoplasm of the follicular cells in frozen human thyroid sections. Studies in the mouse demonstrated for the first time the presence of mEGF within murine thyroids. The mean mEGF concentration in thyroid homogenates was 26.10 ±6.00 ng/mg protein (range 5.50 - 68.00 ng/mg). This was equivalent to 1.5 ng/mg wet weight and was of the order of 20 to 150 times the mEGF concentration previously reported in mouse testes, brain or pituitary. Extracts from the mouse submaxillary gland expectedly contained abundant mEGF (600 - 1220ng/mg wet weight) but there was no correlation between thyroid and submaxillary mEGF content; Sialoadenectomy augmented thyroid mEGF content. Exposure of mice to various hormonal and metabolic manipulations indicated that mouse thyroid and submaxillary mEGF was responsive to thyroid hormone status, androgen status and to changes in dietary iodine. Further studies in newborn mice revealed that their thyroids had begun to t elaborate appreciable amounts of mEGF while the growth factor remained undetectable in their submaxillary glands. In conclusions these mouse indicate that EGF is a normal constituent of human saliva, human urine and of both human and murine thyroid tissues with differinig levels relating to different disease states such as thyrotoxicosis, diabetic nephropathy and end - stage renal failure. Furthermore, evidence has been presented to implicate the thyroid gland as a probable site of EGF synthesis in both man and the mouse. Description: A Thesis in the Department of Medicine, submitted to the Faculty of Clinical Sciences and Dentistry in partial fulfillment of the requirements for the Degree of Doctor of Medicine of the University of Ibadan 1989-04-01T00:00:00Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/543 Title: THE PATHOPHYSIOLOGY OF RESPIRATORY GAS EXCHANGE Authors: OTULANA, B. A. Abstract: Respiratory gas exchange involves the transfer of oxygen from the atmosphere to the metabolizing cell, and the movement of carbon dioxide in the opposite direction. Contributing to this phenomenon are various cardiorespiratory processes including ventilation, gas diffusion, perfusion, and transport and tissue delivery. Three major groups of patients were studied to investigate areas of abnormalities in these processes. Patients with primary pulmonary hypertension (PPM) showed major abnormality in the ventilation-perfusion matching as well as having poor cardiac output, both resulting in low mixed venous oxygen saturation and hypoxaemia at rest. Both exercise and prostacyclin infusion failed to alter the ventilation-perfusion imbalance although the latter caused improvement in arterial oxygenation by improving the mixed venous oxygen as a result of increased cardiac output. Patients with chronic obstructive pulmonary disease (COPD) also showed abnormal gas exchange. It was shown that in this group as well as in the PPH patients, the presence of ventilation-perfusion mismatching and exaggerated phasic variation in pulmonary end-capillary CO2 made estimation of cardiac output using alveolar gas exchange (Fick Principle) imprecise. By contrast to these two groups, recipients of heart-lung transplantation have no afferent innervation to their lungs and hearts. Nonetheless they manifested normal gas exchange at rest. Abnormalities developed on exercise, with suboptimal cardiac response and increase ventilated response. Exercise gas diffusion was also impaired. These studies demostrated the interrelationship of various abnormalities of gas exchange, the knowledge of which are essential for understanding the pathophysiology of disease processes. Description: A dissertation submitted to the University of Ibadan, Ibadan, Nigeria in partial fulfillment for the award of the Degree of Doctor of Medicine (M.D.), Department of Medicine, College of Medicine, University of Ibadan. 1991-01-01T00:00:00Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/344 Title: A SPECTRUM OF IMMUNITY IN TUBERCULOSIS Authors: ONWUBALILI, JAMES KENECHUKWU Abstract: ABSTRACT The variable clinical presentation of tuberculosis would suggest a spectrum of host immune responses to the disease. To investigate this hypothesis, 30 hospitalized patients aged 19 to 61 years (moan 34.4 years) with bacteriologically-proven tuberculosis were studied prospectively clinically and with a representative range of in vivo and in vitro tests of immune function. 73% of patients had pulmonary disease, 70% originated from the Indian Subcontinent, and 50% were vegetarian. Responses were compared with those of healthy controls carefully matched for age, sex, ethnic group and diet. Before treatment, patients were profoundly malnourishedand had significant anaemia, hyponatraomia, hypoalbuminaemia, neutrophil leucocytosis, lymphocytopenia, (predominantly helper T-cell), monocytosis, elevation of sedimentation rate, serum alkaline phosphatase, total globulins and Immunoglobulins G and A. Accelerated skin reactions (6-8 hrs.) to intradermal tuberculin-purified protein derivative were significantly more frequent, and 48hr skin reactions were larger in the patients. Even allowing for the booster effect of repeated tuberculin testing seen in controls, chemotherapy was associated with an increase in tuberculin reactivity. Peripheral blood mononuclear cells from patients were less responsive in vitro to purified protein derivative, but not to potent mitogens. No inhibitory effect was observed when normal mononuclear cells were cultured in patients’ sera. Migration of mononuclear cells, judged by mean random locomotion and casein-stimulated chemotaxis in vitro wan impaired but no differences were observed between patients and controls in spontaneous and interferon-augmented Natural Killer cytotoxicity. No significant differences were found between patients and controls in titers of Interferon-a Induced by Newcastle Disease Virus. However, mononuclear cells from a subset of nine patients produced relatively low titers of Interferons in response to purified protein derivative. In comparison with other patients, this group wascharacterized by lower Interferon-a and Interferon-7 response to virus and mitogens respectively, relative energy to virus and mitogens respectively, relative energy to tuberculin skin testing, depressed in vitro mononuclear cell proliferative response to purified protein derivative, and neutrophil leukocytosis. Two patients, both alcoholic male Caucasians with extensive pulmonary disease, developed acute respiratory failure within two weeks of starting chemotherapy. One of them died. In all other patients, the initially abnormal measurements returned to normal limits for controls during chemotherapy, except that protein malnutrition permitted for at least as long as the nine-month regimen of treatment. It 1s proposed that patients be categorizedinto five groups according to their reactivity to tuberculin-purified protein derivative in the accelerated and delayed skin tests, mononuclear cell proliferation and lymphokine (Interferon-y) production assays. Responses to purified protein derivative were graduated and ranged from a state of hypersensitivity (Croup 1) to one of energy (Croup 5) In a continuous downward gradation. These immunological patterns showed only a weak association with nutritional status, but no association with age, radiological extent or duration of disease, serum antibodies, cell counts or erythrocyte sedimentation rate. These studies indicate a spectrum of Immunological responses In human tuberculosis, analogous to leprosy, but exclusive of a form equivalent to chronic lepromatous leprosy. Description: A THESIS IN THE DEPARTMENT OF MEDICINE SUBMITTED TO THE COLLEGE OF MEDICINE IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF IBADAN 1984-09-01T00:00:00Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/331 Title: PERSONALITY CHARACTERISTICS OF A SAMPLE OF UNIVERSITY FRESHMEN AND FRESHWOMEN Authors: JEGEDE, ROWLAND OLUKAYODE Abstract: ABSTRACT Eight hundred and seventy University of Ibadan freshmen, consisting of 725 males and 145 females, were studied during their first few weeks in the university with the aim of assessing their social and personality characteristics. The following instruments were used: (1) A sixty-five item general questionnaire (GO) covering social- demographic factors, biographic and secondary school background, attitudes and other characteristics; (2) the Health Opinion Survey; and (3) Eysenck Personality Questionnaire. Most subjects had parents who were either Yoruba or Ibo and were predominantly Christians. The parents of the majority of the students were either Illiterate or had little formal education. Half of the subjects came from polygamous homes. Although about two thirds of the students had consulted a doctor during the past 12 months, most subjects reported their current health to be good or excellent. While most of the students reported that they had Intimate friends, they had more difficulty making friends with members of the opposite sex than with persons of the same sex as themselves. The mean scores on the scales of the Eysenck Personality Questionnaire (EPP) were broadly similar to results obtained with samples of British subjects and Nigerian soldiers, although some Important differences from British data could be found. Statistical analysis demonstrated interesting relationships between some of the variables on the general questionnaire. Self¬-assessed recent mental health (SMH) was found significantly associated with (1) whether or not subjects had problems to discuss with a doctor; (2) recent physical health; (3) neuroticism score on the EPQ. Factor analysis of the General Questionnaire yielded 17 factors which accounted for 50.2 per cent of the variance on the GO. Eight of the factors were related to the students' family background, three with health, two with Interpersonal relationships, and the rest with miscellaneous characteristics of the subjects. The GO-derived factors arc, as a group, rather weak predictors of scores on the Health Opinion Survey. A few of the factors are good predictors of self-assessed mental health and Extraversionscores of the EPQ, but the 17 factors are as a group not good predictors of either self-assessed mental health or extraversion. The seventeen factors are fairly weak predictors of Neuroticismscores on the EPO. The first follow-up study which took place 6 months after the Initial study covered a representative sample, that Is one third, of the students who took part in the Initial study. Current self-assessed physical and mental health and history of doctor consultation 12 months prior to admission to the university (all 3 variables were from the Initial study) were not significantly related to whether or not the university health center was visited for treatment. However, all 3 variables except SWI were significantly associated with general neurotic symptom as measured in the first follow-up study. A follow-up study, involving one third of the subjects occurred 15 months after the onset of the initial study. The subjects were randomly selected from the initial sample of 870 students. Scores obtained on a list of 10 common neurotic symptoms were significantly associated with the following initial study variables: (a) self-¬assessed recent physical health; (b) history of consulting a doctor 12 months prior to university admission; (c) self-assessed recent mental health. Desire to see a doctor without actually seeingone aa reported at the follow-up study was also significantly associated with the same 3 variables. A clinical Interview of each member of a randomly selected sub¬sample of 30 students was carried out 26 months after the onset of the Initial study. The main findings were that the subjects resembled United States students studied with similar techniques in their interests, aspirations, object relations and some other respects. In general, the relation between past health history (I.e. before coming to the university) and health history in the university Is consistent with the findings of other workers. The results are discussed in terms of their Implications for personality development; provision of student mental health facilities in the university; adaptation of students to university life and academic achievement; and the value of self-assessment as an Index of mental health. Methodological implications and limitations of the study arc also discussed. Description: A THESIS IN THE DEPARTMENT OF MEDICINE SUBMITTED TO THE COLLEGE OF MEDICINE IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF IBADAN 1979-01-01T00:00:00Z