Showing papers by "University of the Witwatersrand published in 1997"

Critical Discourse Analysis as a Research Tool

Abstract: (1997). Critical Discourse Analysis as a Research Tool. Discourse: Studies in the Cultural Politics of Education: Vol. 18, No. 3, pp. 329-342.

Follicular dendritic cell sarcoma : Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized

Abstract: BACKGROUND The goal of this study was to characterize the clinicopathologic features of follicular dendritic cell sarcoma, a very uncommon neoplasm. METHODS The 17 cases were collected from the consultation and surgical pathology files of the authors, including 8 previously reported cases. The histologic and immunohistochemical features and outcome were analyzed. RESULTS The patients had a median age of 40 years, with a slight female predominance. Seven patients presented with enlarged lymph nodes, and ten presented with tumor in extranodal sites. Two cases were associated with hyaline-vascular Castleman's disease. The tumors had an average greatest dimension of 6.7 cm. The most common histologic feature was a storiform or fascicular array of spindle, ovoid, or polygonal cells with oval nuclei, delicate nuclear membrane, vesicular or granular chromatin, distinct nucleoli, indistinct cell borders, and frequently fibrillary cytoplasm. There were often scattered multinucleated forms. The tumor cells sometimes formed sheets, circular whorls, follicle-like structures, trabeculae, or pseudovascular spaces. There was a sprinkling of small lymphocytes, with or without cuffing around blood vessels. The neoplastic cells were immunoreactive for CD21 (17 of 17 cases), CD35 (17 of 17 cases), desmoplakin (10 of 17 cases), epithelial membrane antigen (14 of 16 cases), S-100 protein (6 of 17 cases), and CD68 (2 of 17 cases), but not cytokeratin. Ultrastructural studies showed villous processes connected by desmosomes. Only one harbored the Epstein-Barr virus. Among 13 patients with a median follow-up of 3 years, local recurrence occurred in 6, metastasis in 6, and 3 died of disease. CONCLUSIONS Follicular dendritic cell sarcoma exhibits distinctive histologic features that permit its presumptive recognition, but a firm diagnosis requires confirmation with special studies. Because it has a significant recurrent and metastatic potential (the latter risk having been previously underestimated), it should be viewed as an intermediate grade malignancy. An intraabdominal location is associated with a particularly aggressive clinical course. Cancer 1997; 79:294-313. © 1997 American Cancer Society.

Melt production during granulite-facies anatexis: experimental data from “primitive” metasedimentary protoliths

Abstract: We conducted fluid-absent partial melting experiments, at 0.5 and 1.0 GPa in the temperature range 750 to 1000 °C, to investigate the influence of bulk rock Mg ? [100Mg/(Mg+Fe)] and the effects of additional TiO2 on the granulite-grade anatectic evolution of relatively magnesian metapelites and metagreywackes. In these experiments, melting began between 780 and 830 °C by the incongruent breakdown of biotite to produce quartz-saturated, granulite-facies residual mineral assemblages in equilibrium with H2O-undersaturated granitic melt. The glass (quenched melt) compositions produced in this study vary little. Generally, the glasses have compositions similar to those of many natural strongly peraluminous leucogranites. The solidus temperatures in both rock types increase with increasing Mg ?, but are unaffected by the presence or absence of a TiO2 component. At 0.5 GPa the metapelites melted at temperatures up to 50 °C lower than the equivalent metagreywackes, but at 1 GPa there was no discernible difference. This study suggests that the fluid-absent solidus has a steep positive dP/dT slope in metapelites and steep negative dP/dT slope in metagreywackes. The pattern of melt production with increasing temperature is strongly controlled by the upper limit of biotite stability. In TiO2-free compositions this was found to increase by 15 to 20 °C in the metapelites and by 30 to 40 °C in the metagreywackes, as a function of increasing Mg ? from 49 to 81. The presence of a TiO2 component increases the upper limit of biotite stability by ∼50 °C in the metapelites and by ∼80 °C in the metagreywackes, over that observed in the equivalent TiO2-free compositions. In consequence, in the TiO2-free samples large pulses of melt (up to 35 wt%) are produced over narrow temperature ranges (as little as 15 °C in these experiments) between 830 and 875 °C. In the TiO2-bearing samples the major pulse of melt production occurs more gradually between 830 and >900 °C.

The Lessons of User Fee Experience in Africa

Abstract: This paper reviews the experience of implementing user fees in Africa. It describes the two main approaches to implementing user fees that have been applied in African countries, the standard and the Bamako Initiative models, and their common objectives. It summarizes the evidence concerning the impact of fees on equity, efficiency and system sustainability (as opposed to financial sustainability), and the key bottlenecks to their effective implementation. On the basis of this evidence it then draws out three main sets of lessons, focusing on: where and when to implement fees; how to enhance the impact of fees on their objectives; and how to strengthen the process of implementation. If introduced by themselves, fees are unlikely to achieve equity, efficiency or sustainability objectives. They should, therefore, be seen as only one element in a broader health care financing package that should include some form of risk-sharing. This financing package is important in limiting the potential equity dangers clearly associated with fees. There is a greater potential role for fees within hospitals rather than primary facilities. Achievement of equity, efficiency and, in particular, sustainability will also require the implementation of complementary interventions to develop the skills, systems and mechanisms of accountability critical to ensure effective implementation. Finally, the process of policy development and implementation is itself an important influence over effective implementation.

The Geographic Distribution of Human Y Chromosome Variation

Abstract: We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or "YAP" element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five "YAP haplotypes" in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 "combination haplotypes". All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions.

Climatic variability and change over southern Africa: a reflection on underlying processes:

Abstract: Quasi-periodicities in annual rainfall totals over southern Africa have been identified; in particular, an approximately 18-year cycle may be related to interdecadal variability in sea-surface temp...

Layering of a liquid metal in contact with a hard wall

Abstract: When a liquid makes contact with a solid wall, theoretical studies1,2,3,4 indicate that the atoms or molecules will become layered adjacent to the wall, giving rise to an oscillatory density profile. This expectation has not, however, been directly verified, although an oscillatory force curve is seen for liquids compressed between solid surfaces5. Here we present the results of an X-ray scattering study of liquid gallium metal in contact with a (111) diamond surface. We see pronounced layering in the liquid density profile which decays exponentially with increasing distance from the wall. The layer spacing is about 3.8 a, which is equal to the repeat distance of (001) planes of upright gallium dimers in solid α-gallium. Thus it appears that the liquid near thewall assumes a solid-like structure similar to the α-phase, which is nucleated on freezing at lower temperatures. This kind of ordering should significantly influence flow, capillary osmosis, lubrication and wetting properties5,6, and is likely to trigger heterogeneous nucleation of the solid.

Large Animals and System-Level Characteristics in River Corridors Implications for river management

Abstract: rocesses structuring riparian corridors can be viewed as a hierarchy, in which primary factors (such as matter, energy, and water) create a spatially extensive and temporally variable physical environment, which becomes habitat for plants and animals. The habitat is further modified by the activities of large animals as they selectively eat vegetation, burrow and wallow in soils, and build dams on streams, among other activities. As a result, the variety of habitats, or "patches," is increased. The vegetation and microorganisms living on the increased variety of habitat patches largely determine the eventual distribution and cycling rates of elements (e.g., nitrogen and phosphorus) as basic population and community processes are carried out (Table 1). In general, ecologists understand how interactions among water, energy, and matter shape the physical characteristics and habitat patches of river corridors, and how vegetation and microbes cycle elements, grow, reproduce, compete, and otherwise function. However, there has been little recognition of the equal importance of large animals in shap-

Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis.

Abstract: Background Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease that occurs in parts of Africa, Asia, and eastern Europe, and that is caused by a recently emerged bunyavirus. Rapid laboratory diagnosis of CCHF infection is essential and is currently performed by virus isolation and serology. Histopathologic studies have been limited to a small number of cases, and little is known about the cellular tropism of CCHF virus and the pathogenesis of this disease. Design We conducted a retrospective case analysis of 12 patients with a diagnosis of CCHF infection, confirmed by virus isolation, who were evaluated at the Special Pathogens Unit, National Institute for Virology, South Africa. The clinicopathologic features of CCHF and the diagnostic role of virus isolation as compared with serology, immunohistochemistry, and in situ hybridization were evaluated. Additionally, the distribution of CCHF virus in human tissues was examined. Results The clinical and histopathologic features of CCHF resemble those of other viral hemorrhagic fevers. Of the 12 patients with virus isolation-confirmed CCHF infection, 5 were positive by serology, 10 by immunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the mononuclear phagocytes, endothelial cells, and hepatocytes are main targets of infection. Association of parenchymal necrosis in liver with viral infection suggests that cell damage may be mediated by a direct viral cytopathic effect. Conclusions The diagnosis of CCHF, suspected by history and clinical features, can be supported histopathologically. However, since the pathologic features resemble those of other viral hemorrhagic fevers, an unequivocal diagnosis can be made only by laboratory tests. The utility of immunohistochemistry as a sensitive and rapid diagnostic modality was established by the high degree of concordance with virus isolation. Infection of mononuclear phagocytes, endothelial cells, and hepatocytes may play a critical role in the pathogenesis of CCHF.

Myocardial Stiffness Is Attributed to Alterations in Cross-Linked Collagen Rather Than Total Collagen or Phenotypes in Spontaneously Hypertensive Rats

Abstract: Background The relative contributions of increases in myocardial collagen, collagen cross-linking, and the ratio of type I to type III collagen to the stiff myocardium in hypertension were determined. Methods and Results We compared the action of hydralazine (0.07 mmol · kg−1 · d−1) with that of captopril (0.22 mmol · kg−1 · d−1) on the left ventricular end-diastolic (LVED) myocardial stiffness constant, k (g · cm−2) and LV myocardial interstitial characteristics in spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) control rats. LVED k (SHR, 27.9±1; WKY, 19.5±1.2; P <.01), myocardial hydroxyproline concentrations (HPRO; μg/mg dry wt) (SHR, 4.19±0.16; WKY, 3.17±0.09; P <.001), and collagen type I/III ratios (SHR, 7.1±0.7; WKY, 2.1±0.2; P <.001) were increased, whereas the percentage of myocardial collagen extracted after cyanogen bromide digestion (an index of cross-linked collagen) was decreased (SHR, 17±3; WKY, 41±4; P <.001) in SHRs compared with WKY controls. Captopril therapy reduced LVED k , myocardial HPRO, collagen type I/III, and augmented collagen solubility (43±4) in SHRs to values similar to those measured in WKY controls. Hydralazine therapy, despite a favorable effect on LVED k in SHRs (20.±1.6, P <.01 compared with untreated SHRs), failed to influence either myocardial HPRO (4.18±0.18) or collagen type I/III (8±1) but did improve collagen solubility (31±2). Conclusions An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.

A unique segment of the hepatitis b virus group a genotype identified in isolates from south africa

Abstract: The preS2/S genes of hepatitis B virus isolated from 29 acutely or chronically infected individuals in the Gauteng province of South Africa were sequenced. Phylogenetic analysis of these sequences in comparison with global isolates from the GenBank database showed that 24 sequences clustered with genotypic group A, three with genotypic group D and one each with genotypic groups B and C. Group A isolates had greater identity with groups D (variation of 6.6%) and E (6.8%) than with the Eastern groups B (7.4%) and C (8.1%) and were most different from group F (11.0%). Of the South African group A specimens, 59.1% clustered with two global sequences to form a discrete segment which we have called subgroup A. The amino acid differences that set these isolates apart from the rest of group A tended to cluster in the preS2 region (amino acids 7, 10, 32, 35, 47, 48, 53 and 54), with a few changes occurring in the major surface antigen (amino acid sites 207 and 209). Analysis of isolates showed that there was a 9-fold higher prevalence of the ay determinant in South Africa than previously reported.

Phylogeography of the sardines (sardinops spp.): assessing biogeographic models and population histories in temperate upwelling zones

Abstract: Sardines (Sardinops spp.) occupy temperate upwelling zones in the coastal regions of the Indian and Pacific Oceans, including locations in Japan, California, Chile, Australia, and South Africa. East and West Pacific populations are separated by vast expanses of open ocean, and northern and southern hemisphere populations are separated by tropical waters which are lethal to sardines. The relative importance of these barriers has been the focus of a long- standing debate between vicariance and dispersal schools in biogeography. Comparisons of a 500 bp fragment of the mitochondrial (mt) DNA control region reveal strong geographic structuring of mtDNA lineages but shallow divergence both within and between regional populations. Regional populations are related to one another in a stepping-stone pattern, the apparent result of a series of Pleistocene dispersal events around the continental margins of the Indian- Pacific Basin. These mtDNA data, combined with an electrophoretic survey of variability at 34 nuclear loci (Grant and Leslie 1996), indicate that the five regional forms of Sardinops (considered separate taxa by most authorities) probably diverged within 500,000 years BP, a much shorter timeframe than predicted by vicariance models based on plate tectonics. High mtDNA haplotype diversity, coupled with an excess of rare alleles in the protein electrophoretic dataset, may indicate exponential growth from a small ancestral population. The mtDNA and allozyme data are concordant with climate records and fossil evidence in portraying regional populations as recent, unstable, and ephem- eral. Regional populations of sardines have probably been extinguished and recolonized over short evolutionary timescales in response to changes in climate and the oceanography of coastal upwelling zones.

Percolation exponents and thresholds obtained from the nearly ideal continuum percolation system graphite-boron nitride

Abstract: Compressed disks made from graphite and, its mechanical but not electrical isomorph, boron nitride as well as graphite-boron nitride powders, undergoing compression, are nearly ideal continuum percolation systems, as the ratio of their conductivities is nearly ${10}^{\ensuremath{-}18}$ and the scatter of the experimental points near the critical volume fraction ${\ensuremath{\varphi}}_{c}$ is very small. The following measurements, with the characteristic exponent(s) in brackets, are made on some or all of the samples in (axial) and at right angles (radial) to the direction of compression, as a function of the volume fraction of graphite (\ensuremath{\varphi}); dc conductivity ($s$ and $t$), dielectric constant ($s$), magnetoresistivity ${(t}_{\ensuremath{\perp}}),$ and noise power $(K).$ The noise power is also measured as function of resistance $(w)$ and volume ${(b}^{\ensuremath{'}}).$ The ${\ensuremath{\varphi}}_{c}$'s obtained for all measurements are consistent and explicable. The results for the exponents are less well understood but, where possible, these results are compared with theoretical predictions and previous experiments. The reasons for the nonuniversality of $t$ are clarified.

Tissue Engineering, Morphogenesis, and Regeneration of the Periodontal Tissues By Bone Morphogenetic Proteins:

Abstract: Tissue engineering is the emerging field of science developing techniques for fabrication of new tissues for replacement based on principles of cell and developmental biology and biomaterials. Morphogenesis is the cascade of pattern formation and the attainment of form of the various organs and the organism as a whole. The periodontium consist of the periodontal ligament, cementum, and alveolar bone. Bone has considerable potential for regeneration and therefore is a prototypic model for tissue engineering. The three main ingredients for tissue engineering are regulatory signals, responding stem cells, and extracellular matrix. Recent advances in molecular biology of the bone morphogenetic proteins (BMPs) have set the stage for tissue engineering of bone and related tissues, including the periodontium. Bone-derived BMPs, with a collagenous matrix as carrier, induced cementum and alveolar bone regeneration in surgically created furcation defects in the primate. It is noteworthy that there was morphogenesis of periodontal ligament and a faithful insertion of Sharpey's fibers into cementum. In the same furcation model, recombinant human osteogenic protein-1 (rhOP-1, also known as BMP-7), in conjunction with the collagenous carrier, induced extensive cementogenesis with insertion of Sharpey's fibers into the newly formed cementum. The observation that BMPs induce cementogenesis and periodontal ligament formation indicates that these proteins may have multiple functions in vivo not limited to cartilage and bone induction. The rapid advances in the molecular biology of BMPs and their receptors bode well for novel strategies to engineer the regeneration of the periodontal tissues.

Recombinant Transforming Growth Factor-β1 Induces Endochondral Bone in the Baboon and Synergizes with Recombinant Osteogenic Protein-1 (Bone Morphogenetic Protein-7) to Initiate Rapid Bone Formation

Abstract: Several members of the bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-beta) families are molecular regulators of cartilage and bone regeneration, although their actual roles and combined interactions in skeletal repair are poorly understood. The presence of several molecular forms suggests multiple functions in vivo as well as synergistic interactions during both embryonic bone development and regeneration of cartilage and bone in postfetal life. Here we show for the first time that recombinant human transforming growth factor-beta1 (TGF-beta1) induces endochondral bone formation in extraskeletal sites of adult baboons. We also show that TGF-beta1 and recombinant human osteogenic protein-1 (OP-1, bone morphogenetic protein-7) synergize in inducing large ossicles in extraskeletal sites of the primate as early as 15 days after implantation. A single application of OP-1, in conjunction with an insoluble collagenous matrix as carrier (5, 25, and 125 microg/100 mg of carrier matrix) induced bone differentiation in the rectus abdominis of the baboon. This level of tissue induction was raised several-fold by the simultaneous addition of comparatively low doses of TGF-beta1 (0.5, 1.5, and 5 microg), which by itself induces bone formation in the rectus abdominis at doses of 5 microg/100 mg of carrier matrix. Combinations of OP-1 and TGF-beta1 yielded a 2- to 3-fold increase in cross-sectional area of the newly generated ossicles, with markedly elevated key parameters of bone formation, and corticalization of the newly formed bone by day 15, culminating in bone marrow generation by day 30. The tissue generated by the combined application of OP-1 and TGF-beta1 showed distinct morphological differences when compared with OP-1-treated specimens, with large zones of endochondral development and extensive bone marrow formation. At the doses tested, synergy was optimal at a ratio of 1:20 by weight of TGF-beta1 and OP-1, respectively. These results provide evidence for a novel function of TGF-beta1 in the primate and the scientific basis for synergistic molecular therapeutics for the rapid regeneration of cartilage and bone.

NO and N 2 O emissions from savanna soils following the first simulated rains of the season

Abstract: Data on the emissions of oxides of nitrogen from the soil during the early part of the wet season are reported for nutrient-rich and nutrient-poor sandy soils at Nylsvley, South Africa. The emissions of NOx and N2O following the first wetting event of the season are elevated relative to subsequent events. The observed high emission rates (76 ng N-NO m-2 s-1) are partially attributed to the sandiness of the soil, which permits NO to diffuse out of the soil rapidly. The pulse of high emissions following wetting is maintained for approximately 72 hours, thereafter continuing at around 20 ng NO m-2 s-1 while the soil remains moist. The initial pulse is suggested to be due to the accumulation of a substrate pool during the dry period, coupled with an inability of plants and microbes to use it effectively during the first few days after wetting. There were no significant differences in the peak or subsequent emission rates for either NO or N2O between two sites of differing nitrogen mineralisation potentials. N2O emissions averaged 8% of NOx emissions. The enhanced emissions of NOx which follow the first wetting after a prolonged dry period do not make a very large contribution to the annual gaseous N emission budget, but could be a significant contributor to the high tropospheric ozone levels observed over southern Africa in springtime.

Optimality Theory and variable word-final deletion in Faetar

Abstract: We examine a pattern of end-of-word deletion in Faetar, a Francoprovencal dialect spoken in southern Italy, considering synchronic variants like [brokələ] ˜ [brokəl] ˜ [brokə] ˜ [brok] ‘fork’. We use the word “deletion” as a synchronic description of the facts; speakers do not always phonetically produce everything in the input form, assuming that the input form is the longest form ever produced. Optimality Theory accounts for this type of variation by positing different rankings of the constraint hierarchy, each of which produces a different optimal output. The predication of alternate constraint rankings within a single dialect, however, poses problems for Optimality Theory as it has been formulated, necessitating numerous grammars for each speaker. We propose floating constraints (Reynolds, 1994), whereby some particular constraint within a single grammar may be represented as falling anywhere within a designated range in the ranking hierarchy. In a previous study (Reynolds & Nagy, 1994) we showed that this model accounts for the distribution of types of output forms produced. Here, we analyze a corpus of 624 tokens from 40 speakers and show that the pattern of distribution of tokens is accounted for as well: the number of rankings that produce each output form is closely correlated to the number of output forms that occur in the data set.

An Analysis of Porphyrin Molecular FlexibilityUse of Porphyrin Diacids

Abstract: The crystal structures of three porphyrin diacid species, [H4OEP](ClO4)2, [H4TPP](ClO4)2, and [H4TMP](ClO4)2, have been determined from low-temperature X-ray diffraction data to delineate how the peripheral substituents of the porphyrin affect the overall molecular flexibility. [H4OEP](ClO4)2 (|Cb| = 0.46 A), [H4TMP](ClO4)2 (|Cb| = 0.67 A, molecule 1), and [H4TPP](ClO4)2 (|Cb| = 0.93 A) show increasingly saddled core conformations with effective D2d symmetry. The mean porphyrin−aryl group dihedral angles in [H4TPP](ClO4)2 and [H4TMP](ClO4)2 (molecule 1) are 27(2)° and 63(13)°, respectively. The steric bulk of the mesityl substituents in [H4TMP]2+ limits the range of observed porphyrin−aryl group dihedral angles to >50° and, consequently, the magnitude of the core distortion. [H4TMP]2+ is therefore less flexible than [H4TPP]2+. Molecular mechanics calculations, using a modified version of MM2(87) and a newly developed force field for porphyrin diacids, correctly predict that the flexibility of meso-tetraar...

Exercise, immunology and upper respiratory tract infections.

Abstract: The literature reveals a paradoxical response of the immune and host defense systems to endurance exercise apparent stimulation following long-term regular training and suppression in response to acute exposure to exhaustive endurance exercise. Several epidemiological surveys have confirmed a clinical manifestation of immunosuppression in the form of increased incidence of upper respiratory tract infection symptoms following participation in competitive marathon and ultramarathon running events. Prerace training status and racing intensity have been related to the incidence of this symptomatology during the postrace fortnight. Nutritional intervention studies have shown the antioxidant nutrient, vitamin C, to be effective in reducing the incidence of upper respiratory tract infection symptoms following competitive distance events. Laboratory studies have revealed this vitamin to be the first line of defense in neutralizing the auto-oxidative activity of phagocytes. It is hypothesized that exercise-induced neuroendocrine stimulation of the oxidative burst in neutrophils increases the rate of release of reactive oxygen species and that these are, in turn, neutralized by high plasma ascorbate levels. Enhancing intrinsic antioxidant defense by increasing exogenous antioxidant intake is thus theorized to be of long-term benefit to serious endurance athletes engaged in heavy training and competition.

Conformational stability of pGEX-expressed Schistosoma japonicum glutathione S-transferase: a detoxification enzyme and fusion-protein affinity tag.

Abstract: A glutathione S-transferase (Sj26GST) from Schistosoma japonicum, which functions in the parasite's Phase II detoxification pathway, is expressed by the Pharmacia pGEX-2T plasmid and is used widely as a fusion-protein affinity tag. It contains all 217 residues of Sj26GST and an additional 9-residue peptide linker with a thrombin cleavage site at its C-terminus. Size-exclusion HPLC (SEC-HPLC) and SDS-PAGE studies indicate that purification of the homodimeric protein under nonreducing conditions results in the reversible formation of significant amounts of 160-kDa and larger aggregates without a loss in catalytic activity. The basis for oxidative aggregation can be ascribed to the high degree of exposure of the four cysteine residues per subunit. The conformational stability of the dimeric protein was studied by urea- and temperature-induced unfolding techniques. Fluorescence-spectroscopy, SEC-HPLC, urea- and temperature-gradient gel electrophoresis, differential scanning microcalorimetry, and enzyme activity were employed to monitor structural and functional changes. The unfolding data indicate the absence of thermodynamically stable intermediates and that the unfolding/refolding transition is a two-state process involving folded native dimer and unfolded monomer. The stability of the protein was found to be dependent on its concentration, with a delta G degree (H2O) = 26.0 +/- 1.7 kcal/mol. The strong relationship observed between the m-value and the size of the protein indicates that the amount of protein surface area exposed to solvent upon unfolding is the major structural determinant for the dependence of the protein's free energy of unfolding on urea concentration. Thermograms obtained by differential scanning microcalorimetry also fitted a two-state unfolding transition model with values of delta Cp = 7,440 J/mol per K, delta H = 950.4 kJ/mol, and delta S = 1,484 J/mol.

Original size of the Vredefort Structure: Implications for the geological evolution of the Witwatersrand Basin

Abstract: — Historically, there have been a range of diameter estimates for the large, deeply eroded Vredefort impact structure within the Witwatersrand Basin, South Africa. Here, we estimate the diameter of the transient cavity at the present level of erosion as ∼124–140 km, based on the spatial distribution of shock metamorphic features in the floor of the structure and downfaulted Transvaal outliers. Taking erosion into account (<6 km) and scaling to original final rim diameter, an estimate of close to 300 km for the rim diameter is obtained. Independent estimates of the final rim diameter, based on an empirical relation of central uplift diameter to rim diameter, spatial distribution of pseudotachylites, and concentric large scale structural patterns, give a similar estimate of close to 300 km for the original final rim diameter. An impact structure of this size is expected to have had an original multi-ring form. At this size, the Vredefort impact structure encompasses the bulk of the Witwatersrand Basin, which appears to owe its preservation to the Vredefort impact. In addition, the Vredefort impact event may have been the thermal driver for some of the widespread hydrothermal activity in the area, which, in recent interpretations, is believed to be a component in the creation of the world-class gold deposits of the Witwatersrand Basin.

Low Serum Testosterone and a Younger Age Predict for a Poor Outcome in Metastatic Prostate Cancer

Abstract: Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.

Effects of training volume on sleep, psychological, and selected physiological profiles of elite female swimmers.

Abstract: Excessive training is reported to cause sleep disturbances and mood changes. We examined sleep and psychological changes in female swimmers across a competitive swimming season, that is, at the start of the season (onset), during peak training period (peak), and after a precompetition reduction in training (taper). For each phase, polysomnographic recordings, body composition, psychological parameters, and swimming performance were obtained. A daily training log and sleep diary were maintained for the entire study period. Sleep onset latency (SOL), time awake after sleep onset, total sleep time (TST), and rapid eye movement (REM) sleep times were similar at all three training levels. Slow wave sleep (SWS) formed a very high percentage of total sleep in the onset (26%) and peak (31%) training periods, but was significantly reduced following precompetition taper (16%), supporting the theory that the need for restorative SWS is reduced with reduced physical demand. The number of movements during sleep was significantly higher at the higher training volumes, suggesting some sleep disruption. In contrast to other studies, mood deteriorated with a reduction in training volume and/or impending competition.

Rufous Oculocutaneous Albinism in Southern African Blacks Is Caused by Mutations in the TYRP1 Gene

Abstract: Summary Oculocutaneous albinism (OCA) is the most common autosomal recessive disorder among southern African Blacks. There are three forms that account for almost all OCA types in this region. Tyrosinase-positive OCA (OCA2), which is the most common, affects ∼1/3,900 newborns and has a carrier frequency of ∼1/33. It is caused by mutations in the P gene on chromosome 15. Brown OCA (BOCA) and rufous OCA (ROCA) account for the majority of the remaining phenotypes. The prevalence of BOCA is unknown, but for ROCA it is ∼1/8,500. Linkage analysis performed on nine ROCA families showed that ROCA was linked to an intragenic marker at the TYRP1 locus (maximum LOD score=3.80 at θ=.00). Mutation analysis of 19 unrelated ROCA individuals revealed a nonsense mutation at codon 166 (S166X) in 17 (45%) of 38 ROCA chromosomes, and a second mutation (368delA) was found in an additional 19 (50%) of 38 chromosomes; mutations were not identified in the remaining 2 ROCA chromosomes. In one family, two siblings with a phenotypically unclassified form of albinism were found to be compound heterozygotes for mutations (S166X/368delA) at the TYRP1 locus and were heterozygous for a common 2.7-kb deletion in the P gene. These findings have highlighted the influence of genetic background on phenotype, in which the genotype at one locus can be influenced by the genotype at a second locus, leading to a modified phenotype. ROCA, which in southern African Blacks is caused by mutations in the TYRP1 gene, therefore should be referred to as "OCA3," since this is the third locus that has been shown to cause an OCA phenotype in humans.

Mutations in the dihydrofolate reductase gene of trimethoprim-resistant isolates of Streptococcus pneumoniae.

Abstract: Streptococcus pneumoniae isolates resistant to several antimicrobial agent classes including trimethoprim-sulfamethoxazole have been reported with increasing frequency throughout the world. The MICs of trimethoprim, sulfamethoxazole, and trimethoprim-sulfamethoxazole (1:19) for 259 clinical isolates from South Africa were determined, and 166 of these 259 (64%) isolates were resistant to trimethoprim-sulfamethoxazole (MICs > or =20 mg/liter). Trimethoprim resistance was found to be more strongly correlated with trimethoprim-sulfamethoxazole resistance (correlation coefficient, 0.744) than was sulfamethoxazole resistance (correlation coefficient, 0.441). The dihydrofolate reductase genes from 11 trimethoprim-resistant (MICs, 64 to 512 microg/ml) clinical isolates of Streptococcus pneumoniae were amplified by PCR, and the nucleotide sequences were determined. Two main groups of mutations to the dihydrofolate reductase gene were found. Both groups shared six amino acid changes (Glu20-Asp, Pro70-Ser, Gln81-His, Asp92-Ala, Ile100-Leu, and Leu135-Phe). The first group included two extra changes (Lys60-Gln and Pro111-Ser), and the second group was characterized by six additional amino acid changes (Glu14-Asp, Ile74-Leu, Gln91-His, Glu94-Asp, Phe147-Ser, and Ala149-Thr). Chromosomal DNA from resistant isolates and cloned PCR products of the genes encoding resistant dihydrofolate reductases were capable of transforming a susceptible strain of S. pneumoniae to trimethoprim resistance. The inhibitor profiles of recombinant dihydrofolate reductase from resistant and susceptible isolates revealed that the dihydrofolate reductase from trimethoprim-resistant isolates was 50-fold more resistant (50% inhibitory doses [ID50s], 3.9 to 7.3 microM) than that from susceptible strains (ID50s, 0.15 microM). Site-directed mutagenesis experiments revealed that one mutation, Ile100-Leu, resulted in a 50-fold increase in the ID50 of trimethoprim. The resistant dihydrofolate reductases were characterized by highly conserved redundant changes in the nucleotide sequence, suggesting that the genes encoding resistant dihydrofolate reductases may have evolved as a result of inter- or intraspecies recombination by transformation.