Thesis (PhD) -- Stellenbosch University, 2002. / ENGLISH ABSTRACT: Children and adults may differ in their immune function. An adequate function of the individual's immune system is crucial to the risk for development of tuberculosis (TB) after infection with Mycobacterium tuberculosis (Mtb). Epidemiological evidence suggests an age-related incidence of TB. Furthermore, the prevailing clinical expression t ' of TB varies between age groups. -The aims of this study were to characterise the cellular immune response at different ages in TB patients and healthy individuals living in a region highly endemic for TB and to relate the findings to the clinical expression of TB in different age groups. A total of 150 persons of different ages were included in this study: 50 TB patients, (identified on the basis of clinical, radiological and microbiological characteristics), 49 healthy Mantoux positive (~15mm) and 51 healthy Mantoux negative (<15mm) subjects. All patients <12yrs were identified as having primary TB and postprimary TB was only diagnosed in patients ~12yrs. Haematologic indices were obtained from all the included subjects and found to be agerelated. With the exception of the absolute lymphocyte counts, all indices were significantly different in TB patients when compared to healthy controls. Whole blood was cultured and stimulated with PHA, PPD and ESAT -6 to measure lymphocyte proliferation and IFN-y, TNF-a, IL-2 and IL-10 production in the supernatants of the cultures. After stimulation with PHA, the production of IFN-y, TNF-a and IL-10 as well as lymphocyte proliferation were all age-related. After stimulation with PPD, age correlated positively with IFN-y production in healthy Mantoux positive subjects< 12yrs. In the age groups <20 yrs, patients produced similar amounts of IFN-y when compared to healthy age-related Mantoux positive controls. TNF-a and IL-2 production were not different between patients and controls. In this whole blood system, measuring any of these cytokines on their own did not differentiate patients from controls at all ages. The ratio of PPD stimulated IFN-y to TNF-a production was significantly less in patients with primary TB and postprimary TB when compared to Mantoux positive controls, irrespective of age. These findings indicate that calculated ratios between several cytokines may be useful markers of disease at all ages. ESA T -6 stimulated IFN -y production did not result in any significant correlation with age, but was significantly less in healthy Mantoux positive subjects ~12 yrs when compared to healthy Mantoux positive subjects <12 yrs and TB patients of all ages. This finding suggests that a positive immune response to ESAT -6 is indicative of recent immunological contact with Mtb. Total IgE was measured in serum. In children <12 yrs these values correlated with age and were highest in healthy Mantoux positive controls, thereby not confirming any inverse correlation between IgE and TB. Age should be recognised as a significant variable in quantitative measurements of cellular immune responses. / AFRIKAANSE OPSOMMING: Die immuunsisteem van kinders en volwassenes kan verskillend wees. Die mate van immuniteit van 'n individu is deurslaggewend vir die risiko om tuberkulose (TB) na infeksie met die Mycobacterium tuberculosis (M tb) te ontwikkel. Epidemiologiese bevindings suggereer dat die insidensie van TB ouderdomgebonde mag wees. V erder verskil die voorkomende kliniese beeld van TB ook tussen ouderdomsgroepe. Die doelstellings van hierdie studie was om die sellulere immuunrespons op verskillende ouderdomme by TB-pasiente en gesonde individue wat in 'n streek met hoogs endemiese TB-insidensie woon te vergelyk. Die doel was ook om vas te stel hoe hierdie bevindings by die kliniese beeld van TB by verskillende ouderdomsgroepe inpas. Daar is l50 persone van verskillende ouderdomme in hierdie studie ingesluit: 50 TBpasiente (geidentifiseer op grond van kliniese, radiologiese en mikrobiologiese karakteristieke), 49 gesonde Mantoux -positiewe (:2':l5mm) en 5l gesonde Mantouxnegatiewe (<l5mm) persone. Alle pasiente <l2 jaar is gediagnoseer met primere TB. Postprimere TB is alleenlik gediagnoseer in pasiente :2':l2 jaar. Daar is aangetoon dat. hematologiese indekse van al die persone in hierdie studie ouderdomsverwant was. Daar was n beduidende verskil in alle indekse van TB-pasiente in vergelyking met die gesonde kontroles met die uitsondering van die absolute limfosiettellings. Kulture van volbloed is gedoen en gestimuleer met behulp van PHA, PPD en ESAT -6 om limfosiet-proliferasie, IFN-y-, TNF-a-, IL-2- en IL-l0-produksie in die supematante van die kulture te meet. Na stimulasie met PHA was die produksie van IFN-y, TNF-a en IL-l0, asook die limfosiet-proliferasie ouderdomsverwant Na stimulasie met PPD het ouderdom positief gekorreleer met IFN-y produksie in gesonde Mantoux-positiewe persone <l2 jaar. In die ouderdomsgroep <20 jaar het pasiente dieselfde hoeveelhede IFN-y geproduseer as gesonde, ouderdomsverwante Mantoux-positiewe kontroles. Daar was geen verskil tussen die produksie van TNF -a. en IL-2 tussen pasiente en kontroles nie. In hierdie volbloed-sisteem het die meet van nie een van hierdie sitokiene op sigself 'n verskil getoon tussen pasiente en kontroles van aile ouderdomme nie. Die verhouding van PPD-gestimuleerde IFN-y- tot TNF-a.-produksie was betekenisvol minder in pasiente met primere TB en postprimere TB in vergelyking met Mantouxpositiewe kontroles, ongeag ouderdom. Hierdie bevindings toon dat berekende verhoudings tussen verskillende sitokiene waardevoile merkers van 'n siektetoestand {TB) by aile ouderdomme kan wees. ESAT-6 gestimuleerde IFN-y-produksie het geen betekenisvoile korrelasie met ouderdom getoon nie. Daar was egter betekenisvol minder produksie in gesonde Mantoux-positiewe persone ~l2 jaar as in gesonde Mantoux-positiewe persone <l2 jaar, asook in vergelyking met TB-pasiente van aile ouderdomme. Hierdie bevinding kan daarop dui dat 'n positiewe immuun respons op ESAT -6 'n aanduiding van onlangse immunologiese kontak met M tb is. Totale IgE was in serum bepaal. In kinders <l2 jaar het hierdie waardes gekorreleer met ouderdomme en die waardes was die hoogste in gesonde Mantoux-positiewe kontroles. Hierdeur is daar nie bevestig dat daar 'n omgekeerde korrelasie tussen IgE en TB is nie. Ouderdom behoort dus as 'n belangrike veranderlike gesien te word in die kwantitatiewe meting van die sellulere immuunrespons.

Although age-related differences in the correspondence bias are often attributed to cognitive decline, the present study found that age-related differences in the correspondence bias were differentially influenced by the participants mood states. Young and older participants completed an attitude-attribution task after having been induced to experience a positive, neutral, or negative mood. Whereas older adults demonstrated the correspondence bias more strongly in the negative mood condition relative to the positive mood condition, young adults exhibited the exact opposite pattern of results. Interestingly, the positive mood manipulation led older adults to be no more dispositionally biased than their younger counterparts. Further, mood and age-related differences in attributional confidence were not eliminated after controlling for individual differences in cognitive functioning.

The aim of this thesis was to investigate inter-individual variability on cognitive task performance in normal older adults. In a review of the cognitive aging literature, the implications of a differential perspective were drawn out in order to establish a theoretical and methodological basis for an investigation into variability. A number of regularly occurring patterns, identified on the basis of available reports in the literature, were used to develop a model of variability (the shuttle model). The empirically-based model was located broadly within a neuropsychological framework, and derived explanatory power from the tenets of brain reserve capacity (BRC) theory. It served to describe the bulge in interindividual variability due to aging (the shuttle bulge), and the shifting occurrence of the bulge in relation to the age axis due to cohort and task-related influences (the shuttle shift). A two phase research study was conducted in order to test hypotheses derived from the model. Phase 1 comprised between-groups analyses of normative data covering a broad range of neuropsychological tests in the domains of attention, memory, language, visual and hand motor skills, in order to examine the progression of variability effects across the adult age range. Phase 2 constituted between and within-groups analyses of normative data from a more limited number of neuropsychological tests. It included the examination of raw score distributions and the characteristics of outliers, and was undertaken to explore more closely the nature of the variability phenomena detected in the first phase of the analysis. Taken together, the results of both phases of the investigation revealed statistically significant variability effects in support of the shuttle model. There was a consistent pattern of increased variability in association with older age regardless of functional modality; frequently, in association with later old age, there was also a subsequent decrease in variability (the shuttle bulge). The age of onset of the initial increase in variability occurred earlier or later (the shuttle shift) as a function of four factors: education, gender, task challenge and age-sensitivity of task. The finding of an earlier onset of variability effects for low education, male gender, high task challenge and high age-sensitivity of task was interpreted in terms of BRC threshold theory. The clinical and social implications of the outcome were discussed with special emphasis on the need for a differential perspective on aging, as a complement to the prevailing normative tradition. It was concluded that the shuttle model has considerable heuristic value. It presents an integrative framework for understanding existing variability data and provides clear indications for future research.

This research investigated the influence of the normal aging process on truly photopic achromatic and chromatic retinal increment threshold over an extensive range of colored targets. It was found that for both achromatic and chromatic retinal thresholds there is a significant correlation between advancing age and the stimulus luminance intensity at threshold across the visible spectrum. This correlation is greater for the short wavelength range than for both the middle and the long wavelength ranges (r² (achromatic)= 0.43; r²(chromatic) = 0.49. In addition, a small exploratory study was completed which examined the role of prereceptoral changes in these age-related differences in color vision function. Results from this preliminary study (Experiment II) support the supposition that prereceptoral factors cannot account for all of the age-related losses that are seen in visual function, particularly in the middle and long wavelength ranges of the visible spectrum. / Arts, Faculty of / Psychology, Department of / Graduate

We examined the effect of daily stress, age, and emotional stability/neuroticism on stress reactivity, using cortisol diurnal rhythms. We used data from the Normative Aging Study (Spiro & Bosse, 2001). The 72 men in this study ranged from 67-93 (M =79.29, SD =4.88). Multilevel modeling showed that higher daily stress predicted flatter cortisol diurnal rhythms, B = .09, p < .001, as did age, B = .01, p < .001, while those higher in neuroticism on the emotional stability/neuroticism measure showed steeper slopes for cortisol diurnal rhythms, B = -.04, p < .001. These results indicate that age and emotional stability/neuroticism levels explain some of the variance in individual differences in stress reactivity and provide a basis for future research focused on the effects of psychosocial variables on physiological outcomes. / Graduation date: 2013

Skeletal fragility is characterized by low bone mass, negative changes in bone microarchitecture, and compromised tissue matrix properties, including accumulation of microdamage. Microdamage accumulates in vivo from daily physiological loading and is targeted for repair through a normal remodeling process, thus preventing microcrack growth and potential fracture. However, impaired remodeling is associated with aging and osteoporosis, resulting in an increased accumulation of microdamage which contributes to reduced bone mechanical properties. The current clinical method for assessing increased risk of fracture involves measuring bone mineral density (BMD) of the hip and spine, locations of trabecular bone where high rates of remodeling occur. The bisphosphonate alendronate (ALN) reduces clinical risk for fracture by significantly increasing BMD, but studies have shown a concomitant reduction in intrinsic properties that may be the underlying cause for recent reports of spontaneous fractures with long-term alendronate use. Another anti-resorptive agent called raloxifene (RAL) is a selective estrogen receptor modulator (SERM) and has been shown to modestly improve BMD while decreasing fracture risk to a similar degree as alendronate. The combination of RAL and ALN as a treatment for osteoporosis may provide the benefits of each drug without the negative effects of ALN. Therefore, the overall goal of this thesis was to address the effects of aging and anti-resorptive agents on the properties of bone through the formation of microdamage. Assessment of age-related effects on bone was conducted through quantification of microdamage progression. It was found that old bone results in greater incidences of microdamage progression, reflecting a compromised tissue matrix with reduced resistance to crack growth. Effects of combination treatment with RAL and ALN were evaluated through biomechanical testing, micro-CT imaging, and microdamage quantification. Results showed improved trabecular bone volume and ultimate load with positive effects on trabecular architecture. Combination treatment reduced the proportion of microdamage that may lead to catastrophic fracture, indicating an improvement in the local tissue matrix properties.

published_or_final_version / abstract / Psychology / Master / Master of Philosophy

published_or_final_version / Medicine / Master / Master of Medical Sciences

The objective of this dissertation was to study the disposition and absorption of riboflavin and ascorbic acid in healthy male subjects as a function of age. Deficiencies of these vitamins have been found in the elderly and malabsorption is suspected in this population. Absorption of riboflavin was examined by administration of an oral dose of 200 mg of riboflavin-5'-phosphate (FMN) and disposition was studied following a 30 min constant rate IV infusion of FMN equivalent to 25 mg of riboflavin. Ascorbic acid absorption was examined by administration of a 5 g oral dose and disposition was studied following a 1 g IV dose. Test doses of these vitamins were administered to subjects ranging in age from 33 to 85 years. High performance liquid chromatographic assays were developed for the determination of riboflavin and ascorbic acid in plasma and urine. The method for riboflavin separated FMN and flavin adenine dinucleotide under isocratic conditions. Quantification of the three flavins was achieved by fluorescence detection. The assay system for ascrobic acid used a postcolumn reaction for the fluorometric detection of a dehydroascorbic acid derivative. This method used isoascorbic acid as the internal standard. Finally, similar specificity between a "methoxyaniline" colorimetric method and the chromatographic method was observed for the quantification of ascorbic acid in plasma and urine. Albumin plasma concentration and riboflavin protein binding were decreased with age (p < 0.05). The in vitro stability of ascorbic acid in whole blood and plasma decreased with age (p < 0.05, n = 17). The results of this study indicate no age-related alterations in parameters associated with the gastrointestinal absorption of these vitamins. Increased relative renal excretion of riboflavin with age may explain the deficiency of this vitamin. On the other hand, ascorbic acid deficiency with age may be explained by decreased stability of the vitamin in blood.

Prior research in L2 reading has shown that adult ESL readers tend to lack in the use of reading strategies, failing to utilize contextual clues or their background knowledge base. In addition, studies demonstrated that when the adult readers who are highly competent in L1 reading read in L2, they become inefficient, "text-bound" readers, failing to utilize their effective reading strategies in L1. The present study investigated adult L2 readers' processes of reading in relation to their perceived view of L2 reading, in an attempt to explore the underlying factors related to "text-bound" processing in L2 reading. Two specific research questions were raised for investigation: (1) what is the relationship between an L2 reader's perceptions about L2 reading and his or her reading processes in L2?; (2) what is the relationship between an L2 reader's perceptions about reading (both in L1 and L2) and his or her transfer of reading strategies from L1 to L2 reading? A significant correlation between the perception and actual processing pattern was hypothesized for both questions within the three theories of reading: the metacognitive, the psycholinguistic, and the schema/interactive theory. These three theories of reading provided the theoretical bases for the study. The study consisted of two phases. In the first phase, a survey was conducted with 139 adult ESL readers who responded to a questionnaire developed to tap L2 readers' perceptions about reading and their actual processes while reading magazines in English. Their responses were statistically analyzed to test the research hypotheses. In the second phase, a case study method was utilized for further exploration with six readers chosen from the survey's respondents. Two meetings with the researcher were held with each of the six subjects to further probe their perceptions about L2 reading, and their actual reading processes while they read an article from a chosen magazine. The results indicated that the more linguistic perceptions an adult L2 reader has, the more text-based processing he or she employs. It was also found that the greater the difference perceived by the reader between L2 and L1 reading, the greater the difference between his or her interaction and transaction with L2 text compared to L1 text.