OpenUCT is the open access institutional repository of the University of Cape Town (UCT). It preserves and makes UCT scholarly outputs digitally and freely available, including theses and dissertations, journal articles, book chapters, technical and research reports, as well as open educational resources.
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Assay of neural differentiation transcripts using genomic techniques: acetylcholinesterase transcripts in aganglionosis coli in humans
(1997) Purves, Tertia Deborah; Purves, LR; Henderson, HE
Application of mRNA analysis technologies, as a technique for protein detection, for the provision of information regarding gene expression and cellular function is an important new diagnostic tool and enhances the information gained from immuno-and enzymehistochemical detection of proteins. A unique opportunity to apply genomic technologies to an unresolved clinical problem was provided by the availability of colonic material from patients with Hirschsprung's disease (HD). HD is a relatively common condition (1:5000 live births) characterised by aganglionosis of the myenteric and submucosal plexuses of the distal colon. The pathophysiology of the disease is unknown but it is thought to arise due to a failure of neural crest cells to migrate to the distal colon during embryogenesis. It is characterised by a striking quantity of AChE enzyme activity in the distal aganglionic colon compared to much lower levels in proximal ganglionic colon as well as in normal colonic tissue. This difference in AChE enzyme activity was investigated using the mRNA analysis technologies of quantitative RT-PCR and RNA primed in situ labelling (PRINS) to detect the specific mRNA transcript, E4,6 AChE mRNA, responsible for the AChE protein. Due to the striking AChE picture there was a good chance of detecting the cells involved such as primitive or undifferentiated ganglion cells, if the corresponding mRNA was made locally. Cell lines were used as initial test vehicles to validate the use of these techniques. Quantitation of the specific transcript using a specially constructed internal standard in the RT-PCR reaction proved both reliable and reproducible and indicated a higher level of expression in K562 cells than N2a cells. The transcript was localised using the PRINS reaction in K562 cells but not in N2a cells indicating a lower limit of mRNA for the technique to be applicable. Analysis of colonic tissue from HD patients proved to be more difficult and the E4,6 AChE mRNA was quantitated in only 1 out of 4 patients who expressed higher levels of mRNA in aganglionic than ganglionic colonic tissue, although in situ localisation of this transcript in colonic tissue was unsuccessful. These techniques require much optimisation and must take into account the half-life of mRNA, mRNA stability and post-translational modification of proteins. However, this lack of detection of AChE mRNA in the colon supports the contention that the origin of the AChE protein is extrinsic to the colon, originating of necessity in the perikaryon of neurons located outside the colon. The technique of using specific mRNA detection to widen the understanding of the genetic programme of cells is feasible and should provide a valuable new tool in the diagnostic pathology laboratory once all the problems have been resolved.
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Open Access
Locating susceptibility genes in Myasthenia Gravis: a trans-racial approach
(1998) Heckmann, Jeannine Mariette; Eastman, R
Myasthenia gravis is an autoimmune disease in which antibodies directed against the muscle acetylcholine receptor result in muscle fatiguability and weakness. The clinical phenotype amongst three South African populations was initially studied in anticipation of a molecular study to locate susceptibility genes contributing to the manifestations of seropositive disease. The disease patterns in patients from Mixed-Ancestry, Black and Caucasian populations were essentially similar. Two subsets of patients were then studied at the molecular level; those with disease onset before the age of 40 years, and those with later onset. The HLA-region on chromosome 6, which has shown associations with different loci in Caucasian subsets, as well as genes encoding two muscle subunits [the alpha- and epsilon subunit of the acetylcholine receptor (AChR)], were studied for disease-allele associations using polymorphic markers such as HLA antigens and RFLP markers in the HLA-region, and microsatellites in all three regions. Myasthenic subjects from two populations [South-African Mixed-Ancestry (n= 58) and Black (n= 21) subjects] were studied in a population-based study. A family-based association and linkage study, using affected-family based controls and allele transmission disequilibrium analysis respectively, in Caucasian simplex- (n= 33) and multiplex families (n= 16), complemented the population studies. Thus, up to sixteen loci spanning the HLA region were investigated for allele associations in early-onset - and late-onset myasthenia gravis, in a case-control study in the three populations. The study was then extended to a linkage analysis using the transmission disequilibrium test as well as allele sharing analysis in a small number of sib pairs. The same strategy was followed to analyse a microsatellite within the first intron of the alpha-subunit of the acetylcholine receptor gene and one 5' to the initiation codon of the epsilon-subunit, to test disease association. The HLA-region in the early-onset subset showed a consistent moderate to strong association with the HLA-B8 allele in all three populations, and less consistently, associations with loci in the region stretching between the HLA-B and TNF loci. In the two South African populations the high relative risks for developing disease were due to a scarcity of the HLA-B8 allele in the control populations rather than to such high prevalences in the patients as are seen in the Caucasian patients. An alternative to the HLA-B8 allele but sharing amino acid sequence motifs with -B8, was thus sought by scrutinising the amino acid sequences of their non-B8 alleles, but not found. The late-onset subset showed an association with HLA-DR5 in two of the three populations (Mixed-Ancestry and Caucasians), and the association extended to the HLA-DQ locus (-DQ7) in Caucasian patients. The Black late-onset sample was too small to yield informative results although all three populations also showed associations with rare alleles at one of the marker loci flanking the TNF locus. A second susceptibility locus was confirmed at the alpha-subunit of the muscle acetylcholine receptor when positive associations with a marker locus (HB) in both subsets of Caucasian and Black myasthenics patients and, linkage in Caucasians, supported the results of a previous study in French Caucasians (Garchon et al. 1994). Preliminary evidence of a possible epistatic effect between the alpha-subunit locus and the HLA class II region (HLA-DR5) was found in the small sample of late-onset myasthenic patients. A recent report, albeit with a different class II haplotype (HLADQAl *O 101 and DR3 combination) in both subsets of myasthenics, also suggests epistasis between these two loci (Djabiri et al. 1997). There was no evidence for association of the epsilon-subunit with either subset of myasthenia gravis.
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Open Access
'n Studie van Franz Liszt se Prelude en Fuga op B-A-C-H vir orrel met spesifieke verwysing na die verskillende uitgawes van die werk
(1998) Nell, Mario Daniel; Smith, Barry
In hierdie tesis word een van Liszt se belangrikste orrelwerke, die Prelude en Fuga op B-A-C-H, ondersoek en ontleed as voorbeeld van sy orrelstyl en om sy bydrae as orrelkomponis te bepaal. Daar word eerstens na Liszt as orrelkomponis gekyk en 'n opsomrning van sy bydrae tot die orrelrepetorium word verskaf Hiema word sy orrelstyl ondersoek en word gekyk na die verskillende orrels wat moontlik 'n invloed hierop kon he. In hoofstuk 3 word die Prelude en Fuga op B-A-C-H ontleed as manifestasie van Liszt se musiekstyl in die algemeen, terwyl Hoofstuk 4 die verwerking van hierdie werk vir klavier ondersoek om te sien watter aanpassings die komponis moes maak. Hoewel hierdie werk van Liszt reeds deur talle uitgewers uitgegee is, is die verskillende uitgawes uiteenlopend en heel dikwels teenstrydig as dit kom by aanduidings in die partituur. Di~ uitgawes wat in hierdie tesis bespreek en vergelyk word, is die wat vrylik in die mark beskikbaar is en dus algemeen deur uitvoerders gebruik word, naarnlik die uitgawes Dover, Musica Budapest, Neue Musik ag Winterthur, Nuwe Liszt, Novello, Peters en Universal. 'n Vergelyking van die verskillende uitgawes geskied aan die hand van tempi-, toonsterkte-, karakter-, partituur-, artikulasie- en manuaalaanduidings. Aandag word ook gegee aan die tonale kleuring, dit wil se die registrasie van die komposisie, asook Liszt se verwerking daarvan vir die klavier en hoe hy die styl van die werk daarvoor moes aanpas. In Hoofstuk 5 word daar gekyk na die verskillende uitgawes van Liszt se orrelwerke en weer spesifiek na die Prelude en Fuga op B-A-C-H verwys. Aangesien sommige uitgawes uiteenlopend is, is gepoog om die belangrikste bronne van elke uitgawe vas te stel en ook 'n vergelyking te tref tussen hierdie uitgawes wat tempi-, toonsterkte-, karakter-, partituur-, artikulasie- en manuaalaanduidings betref Die notetekste van die verskillende uitgawes van die Prelude en Fuga op B-A-C-H word in die bylae verskaf. In this thesis one of Liszt's most important organ works, the Prelude and Fugue on B-A-C-H, has been examined and analysed in order to determine his organ style and evaluate his contribution as a composer for the organ. " Initially the thesis looks at Liszt as an organ composer and a summary is provided of his contribution to the organ repertoire. This is followed by an analysis of his style, taking into account the different organs which could possibly have had an influence on his work for this instrument. In Chapter 3 the Prelude and Fugue on B-A-C-H is analysed as a manifestation of his " musical style in general, while Chapter 4 attempts to explore the adaption for piano in order to determine what changes the composer had to make. Although this work of Liszt's has already been published by a myriad of publishers, the editions differ considerably and often contain contrary indications in the score. The editions that are discussed and compared in this thesis are those which are freely available on the market and are therefore often used by performers, viz the Dover, Musica Budapest, Neue Musik ag Winterthur, New Liszt, Novello, Peters and Universal editions. These editions are compared in terms of their tempi, tonal strength, character, score and articulation and manual indications. Attention is also paid to the tonal colour, ie the registration of the composition, as well as Liszt's adaption for the piano and how it had to be changed for the latter. In Chapter 5 the different editions of Liszt's organ works are compared, with specific reference to the Prelude and Fugue on B-A-C-H. Since some of the editions differ considerably an attempt has been made to determine the most important sources of each edition and to draw a comparison between these editions in terms of tempi, tonal strength, character, score and articulation and manual indications. The scores of the different editions of the Prelude and Fuge on B-A-C-H are included in the schedules.
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Open Access
Neural and humoral control of muscle atrophy
(1998) Gibson, Alan St Clair; Lambert, Mike
The aim of this thesis was to examine the relative input of neural activity changes and humoral factors in the control of muscle atrophy, which is a consequence of anterior cruciate ligament (ACL) deficiency. The first study was an epidemiological investigation of injuries in the Cape Town sporting community. Two hundred and sixty questionnaires were randomly distributed to individuals involved in a variety of different sports, in order to assess the incidence of sport-induced injuries, nature of the injuries and rehabilitation modalities used. Injuries occurred in most anatomical regions, with the knee joint being involved in 18% of injuries. The majority of respondents went directly to a physiotherapist after suffering their injuries. In contrast, no injuries were treated by a biokineticist. and 47% of respondents were unsure of the role of the biokineticist. Twenty two percent of respondents were dissatisfied with the treatment of their sporting injuries. It was concluded that the multi-disciplinary approach to sport injury management was not being correctly utilised in the Cape Town community. The second study was an epidemiological investigation of techniques used by Orthopaedic surgeons for repair and rehabilitation of ACL injuries. Four hundred and seventy five questionnaires were distributed to all Orthopaedic surgeons in South Africa. A 77% questionnaire return rate occurred. A significantly higher proportion of state hospital respondents used standard or modified parapatellar arthrotomy procedures rather than arthroscopy techniques when compared to private respondents (p < 0.01 ). Similarly, the majority of these surgeons preferred to immobilise the damaged limb for 6 weeks or longer as compared to private surgeons, who more often would use accelerated rehabilitation schedules. The large majority of all respondents (79%) used bone-patellar tendon-bone grafts as their material of choice for ACL replacement. It was concluded that registrar Orthopaedic surgeons may be learning techniques different to those used in the private sector, and that this concern could be resolved by involving the private sector Orthopaedic surgeons in registrar training where deficiencies existed. The third study was an epidemiological investigation of pneumatic tourniquet use and 11 perceptions of complications which may arise from tourniquet use. The subjects in this study were the same Orthopaedic surgeons described above in study two. Although the large proportion of respondents were aware of the hazards of excessive duration of tourniquet use and the complications of subsequent underlying muscle ischaemia, a large proportion of respondents used high tourniquet inflation pressures and were not as aware of the side effects of tourniquet pressure in causing side effects. It was similarly found that those subjects who did not believe the pneumatic tourniquet caused underlying complications did not check the pneumatic tourniquet apparatus as regularly as those respondents who were aware of the possibility of complications. It was concluded that this finding was of some concern because of the fact that a number of studies have shown that malfunctioning gauges can under-read the true pressure significantly, and because it has been demonstrated that a large proportion of hospital tourniquet apparatuses are faulty in certain hospitals. The fourth study was a study of anthropometrical and isokinetic quadriceps and hamstrings strength and endurance capacity in normal subjects (n=10), and an assessment of the relationship between these variables tested. A strong correlation was found between lean thigh volume (LTV) and both quadriceps and hamstrings isokinetic concentric and eccentric peak torque and total work capacity for both maximal strength and endurance capacity testing. This was particularly evident for the relationship between quadriceps eccentric peak torque capacity and LTV (r=0.98). There were no significant differences between limbs for all variables tested. The fifth study examined functional, anthropometrical and strength deficits in chronic ACL deficient subjects. There were significantly lower LTV and isokinetic strength measurements in the ACL deficient limb compared to the normal limb (n=20). The eccentric component of strength testing was particularly affected, showing lower values for eccentric peak torque than concentric peak torque. The relationship between LTV and eccentric peak torque was lower than that elicited both in normal subjects (r=0.66) and that elicited in the normal contralateral limb. These changes were reflected in changes in the subjects' lifestyle, with the majority of subjects having to downgrade their lifestyle, and a number experiencing frequent episodes of giving way or collapse of the ACL deficient limb. It was concluded that the loss of the quadriceps muscle size was not the only responsible factor for eccentric peak torque losses, and that perhaps a protective neural inhibition of quadriceps function, and particularly maximal eccentric contraction during ballistic isokinetic testing, exists. The sixth study examined subjects with partial (n=7) as compared to complete (n=12) chronic ACL deficiency. Both partial and complete groups showed similar inhibition of quadriceps eccentric function, and it was thus concluded that this functional loss may be related to anterior tibial translation in the damaged ACL limb rather than loss of the ACL itself. It was also found that hamstrings strength was greater in the complete ACL deficient subjects compared to partial ACL deficient subjects, which indicates that in the ACL deficient limb the hamstrings act to a greater degree as secondary stabilisers of the knee joint preventing anterior tibial translation . The seventh study examined subjects whose ACL had been repaired at least a year or more previously (n=8}. Despite these subjects having improved subjective functional ratings, the correlation between the ACL reconstructed quadriceps eccentric peak torque and LTV was similar to that in the ACL deficient limb (r=0.50), and significantly decreased eccentric peak torque capacity in the affected limb. This finding indicated that ACL reconstruction does not improve quadriceps strength function and strengthened the hypothesis of a mechanoreceptor mediated quadriceps inhibitory mechanism. The eighth study examined subjects in the acute phase after ACL rupture (n=6), to assess whether these changes were a chronic adaptation to ACL deficiency or occurred directly as a consequence of the injury. In these subjects an almost identical pattern of anthropometrical and isokinetic strength deficits occurred as in the chronic ACL deficient and ACL groups. This finding indicated that these strength deficits were nor a late-onset compensatory mechanism but occurred directly as a result of the ACL rupture. Similarly, these findings were unlikely to have been caused simply by pain-induced nociceptor stimulation, as they remained present in the pain free, chronic ACL deficient subjects described earlier. The ninth study examined the underlying muscular pathology in the acutely injured ACL subjects described earlier (n=6). Compared to control subjects (n=10), the ACL deficient subjects demonstrated visible type I and type II muscle fibre atrophy associated with fibrosis, fibre degeneration and vacuolar degeneration. Although both fibre types were damaged, type I fibres were atrophied to a greater degree, with the ratio of type I/type II fibres decreasing. Similarly, citrate synthase activity decreased while phosphofructokinase activity increased. 13 This indicated that either neural firing patterns in the musculature were altered, that piezo- electric humeral signals induced by inactivity, or a combination of both these factors caused pathological changes in the underlying musculature. The presence of angulated fibres and fibre splitting, both pathognomonic of denervation atrophy, were observed in the ACL damaged subjects muscle samples, indicating that perhaps neural activity pattern changes are more responsible for the changes in the musculature. The tenth study examined the effects of ACL resection, immobilisation and denervation on underlying musculature in a rat model (n=72). In the ACL resected group, similar changes to the human group was found, with fibrosis, fibre degeneration and angulated and split fibres present in both superficial and deep vastus rat muscles. In this rat model, both fibre types showed atrophy, with type I fibres showing a greater degree of atrophy than type II fibres. Similar findings occurred in rats whose femoral nerve was resected. In contrast, both type I and type II fibres were severely and equally affected in spica-immobilised rats, and none of these changes occurred in sham-operated rats. It was concluded that ACL resection, in the absence of any other pathological intervention, leads to quadriceps muscle atrophy which resembles a denervation rather than an immobilisation atrophy. The eleventh study examined neural activity pattern changes during eccentric quadriceps muscular activity in ACL deficient (n=20), ACL repaired (n=8) and recently injured (n=6) ACL subjects using electromyography (EMG) techniques. In the vastus medialis musculature, the neural activity patterns were unequivocally altered, with less neural activation of the underlying musculature. It was noted that these changes were present only in eccentric activity, while during concentric muscle function no significant changes occurred. This indicated that these EMG changes could not be caused by altered signals occurring in damaged muscle, as the concentric component was normal. These findings strongly support the theory that a neural inhibitory pathway rather than humeral piezo-electric changes, are primarily responsible for the LTV changes, strength deficits and muscle pathology described earlier. The twelfth study examined quantitative and qualitative changes in EMG activity during step down activity in ACL deficient (n=20); ACL repaired (n=8) and recently injured (n=6) ACL subjects. Surprisingly, there were no significant qualitative and quantitative changes in the ACL group. Rather, gait pattern changes were found in the ACL repaired group. This group 14 demonstrated an avoidance pattern of movement, with the normal limb being activated to a greater degree during step down activity, perhaps to unload the affected limb. These findings indicated that different mechanisms are involved in these changes compared to the quadriceps inhibition response described earlier, one being a complex excitatory response and the other a reflexive inhibitory response. One must speculate that perhaps multiple different pathways are activated by ACL damage, some of which are permanent reflex responses and others learned response modification induced by the subsequent reconstruction and rehabilitation. In summary, this thesis describes neural activity changes in the quadriceps musculature of ACL deficient subjects with associated eccentric isokinetic strength deficits and a dissociation in the strong relationship between LTV and strength capacity described in normal subjects. These changes are not altered by ACL reconstruction, and occur in the acute phase after ACL injury. These neural activity changes induce pathological fibre atrophy in the underlying quadriceps musculature which are a consequence rather than a cause of the altered neural activity patterns. Gait pattern changes in ACL reconstructed subjects during step down activity indicate that there may be more than one neural recruitment pattern changes induced by ACL damage, reconstruction and subsequent rehabilitation.
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Open Access
The politics of technology in higher learning: the role of information technology in the transformation of higher education in South Africa
(1998) Rodenacker, Franz; Simons, Mary
The objective of this research is to investigate the effects of the increasing use of IT for learning in HE generally, and with respect to the aims for the transformation of HE in South Africa specifically. This informs the formulation of principles for a socially-compatible implementation and use of IT in HE in SA The central question guiding this research is what are likely effects of the increasing use of IT in HE, and how they relate to the aims for HE as set out by South African policy makers. This objective is achieved through a review of the theoretical work pertaining to the relationship between technology and society; an examination of the arguments for IT brought forwards by proponents; a thorough examination and critique of IT by use of writings of substantivist, educationalists and educational technology experts; and by an examination of the aims for HE as formulated by South African policy makers, the reasons for the use of IT in South Africa and a comparison of these factors with social realities. The social realities of interest are the poor preparation of some South Africans for HE and the inequitable access structures to IT and telecommunications in particular. The research argument is that the reasons for the use of IT in HE are significant indicators for potential effects of IT on HE. The motivations for the use of IT are closely related to the financial pressures that the expansion of HE exerts on the government and institutions for higher learning alike. IT is seen as the means of easing these financial pressures by increasing the economic efficiency and effectiveness of HE. This thesis argues that HE-institutions may thus place greater emphasis on their economic efficiency and financial effectiveness, and suggests that this may be to the detriment of objectives that are not directly economically significant. The integration of IT into South African HE-institutions thus has the potential to have significant adverse effects on some of the aims and goals of transformation of HE in SA This thesis is based on a thorough examination of the literature on IT in its application for learning in HE, supported by an in-depth interview and frequent participation in electronic discussion forums. Data collection involved library searches, e-mail links, an interview and Internet searches.