PhD

dissertationThe Smith diffuse variant and the wound mucoid strain of Staphylococcus aureus were shown to exhibit serologically distinct capsules. The Welwood and K-6 strains of S. aureus were tested to determine their capsular types. Both Welwood and K-6 were found to be representative of the Smith capsular type. An additional 13 isolated of S. aureus from mice were tested. Gel double-diffusion tests and immunoelectrophoresis of staphylococcal antigens disclosed the probable existence of at least two additional capsular types. Passive hemagglutination tests carried out with cells sensitized with 1 mg of antigen per ml showed a multiplicity of cross-reacting antigens. However, cells sensitized either with 0.1 or 0.05 mg of antigen per ml and reacted with antisera absorbed with 10 or 1 ug/ml of homologous antigen showed the presence of specific antigen of extracts from each strain of S. aureus. Corroborative evidence for multiplicity of capsular types was obtained by the specific capsular reaction. At least four capsular types of S. aureus were found. The prototypic strains for these antigens are the RLM or wound strain, the Smith diffuse strain, and mouse strains designated 36T and 43R. It was proposed to designated these types 1, 2, 3, and 4, respectively. Three serologically active components in partially purified capsular material (PPCM) from the wound strain S. aureus were separated by column chromatography on Sepharose 6B. Chemical analyses of the components following acid hydrolysis showed no significant qualitative differences in their amino acid contents. The 73-80 ml pool showed 37% glucosamine and 36% reducing sugars. A significant difference was noticed in the glucosamine and reducing sugar values of the 73-80 ml pool as compared with the other pools. Immunoelectrophoretic analysis showed the 73-80 ml pool contained a single serologically active component which migrated anodally. Gel diffusion investigations confirmed the presence of the same serologically active component in PPCM by showing the present of a reaction of identity between the PPCM and 73-80 ml pool when they were reacted with specific antiserum.. Antiserum absorption studies revealed that the 58-72 ml, 73-/0 ml, and 81-100 ml pools all contained capsular antigen. The most active pool in the anticapsular antibody absorption test was the 73-80 ml pool. This fraction was twice as active as the 58-72 ml pool and eight times more active than the 81-100 ml pool in the absorption of anticapsular antibodies

MS

thesisThe term specific capsular reaction has been used in this thesis instead of capsular swelling reaction or "quelling" because no data were available to indicate that an increase in capsular size occurred when specific antiserum and encapsulated staphylococci were combined. When specific antiserum and organisms were mixed, the antigen-antibody reaction occurred only at the surface of the capsule. However, the cell wall, cytoplasmic matrix, and nuclear material were not affected. The present study showed that erythrocytes sensitized with capsular material prepared from the wound strain of S. aureus were agglutinated by homologous staphylococcal antiserum. Gel double-diffusion tests showed three distinct precipitation lines when the partially purified capsular Material was diluted 1:1,000 in buffered saline pH 7.2 and only one precipitation line when the partially purified capsular material was diluted 1:10,000. However. since the partially purified capsular material used for the sensitization of rabbit erythrocytes was diluted 1:10,000 in buffered saline and since it showed only one precipitation line at this concentration in gel double-diffusion tests. it was justifiable to ascribe the sensitization of rabbit erythrocytes as probably due to the capsular antigen. The specificity of the hemagglutination reaction was clearly shown by inhibition of hemagglutination by microgram quantities of the partially purified capsular material prepared from the wound strain of S. aureus. Capsular material from the encapsulated wound strain and a nonencapsulated variant of it was detected in culture supernatant fluids by inhibition of indirect hemagglutination. The encapsulated wound strain retained capsular material on its surface as shown by the specific capsular reaction while the nonencapsulated variant did not. The increased virulence of the encapsulated wound strain for embrjonated hens' eggs as compared to the nonencapsulated variant derived from it was believed to be due to a better retention of capsular material. In the present work the specific capsular reaction was used exclusively to demonstrate capsules on the Smith diffuse variant and to demonstrate their absence on the compact variant of the Smith strain of S. aureus. Morse (1962a), Koenig (1962) and Modd and DeCourcy (1965) were unable to elicit a specific capsular reaction using the Smith strain. but workers in this laboratory succeeded in this endeavor by employing both rooster and rabbit antistaphylococeal serum. Morse used the Smith diffuse strain of S, aureus in all of his experiments (personal communication). India ink preparations of this strain showed that the organism was surrounded by an envelope structure (Morse, 1962a). Mudd and DeCourcy (1965) reported that the encapsulated Smith strain of S.aureus grew as a compact colony in normal rabbit serum. He reported that this staphylococcus was also surrounded by an envelope structure as demonstrated by the India ink method. Although this thesis does not dispute the validity of these observations, his data tend to obscure the basic question, namely, whether or not the virulent form of the Smith strain is encapsulated and grows as a diffuse colony in serum or plasma soft agar. Growth of the Smith strain of S. aureus in normal rabbit serum soft agar as a compact colony has usually been interpreted (Koenig, 1962; Koenig et al., 1962a, 1962b; Koenig and Melly, 1965) as an indication of nonencapsulation and characteristic of the avirulent form of the Smith strain of S. aureus, but Mudd and DeCourcy (1965) reported that their culture of the encapsulated Smith strain of S. aureus grew as a compact colony in normal rabbit serum soft agar. Electron photomicrographs of the Smith diffuse variant of S. aureus showed the presence of a capsule (Koenig and Melly, 1965). However, Koenig (1962) was unable to find any difference in the diffuse or compact Smith strains of S. aureus when these strains were examined in India ink preparations. To use wet India ink preparations as the only criterion for the demonstration of capsules of S. aureus could lead to confusion. It should be re-emphasized that the most definitiive method for the demonstration of capsules of S. aureus is the specific capsular reaction. In his research Mudd (1965) maintained that the encapsulated Smith strain of S. aureus should be considered as the prototype of encapsulated S, aureus strains and that the wound strain isolated in this laboratory should be considered as a representative of a phenomenon which he called the extracellular peripheral precipitation reaction (EPPR). The latter term, EPPR, seems to be only a circumlocution used to describe the specific capsular reaction,, Mudd and DeCourcy (1965) would exclude the wound strain of S. aureus as being truly encapsulated because they would restrict true encapsulation to virulent naturally occurring strains. The wound strain in its encapsulated state was obtained by the method employed by Bigger„ Boland and 0'Mera (1927). Its virulence in embryonated hens' eggs is indisputable (Wiley. 1961)„ Naturally occurring encapsulated S. aureus of the wound mucoid type-have been isolated from rabbits, roosters, mice, and humans. Each isolate exhibited a positive specific capsular reaction upon initial isolation (Wiley, 1961, 1963). Wiley (1961) devised and employed a virulence test in embryonated hens' eggs which is well suited to the testing of the virulence of S. aureus isolates. In this test, the wound strain behaved as a virulent strain with an LD50 of less than 500 organisms. The finding of anticapsular antibodies that react with the wound strain in normal rabbits, roosters, mice, and humans (Wiley, 1961, 1963) further supports the validity of this position. Apparently, the wound strain is a major capsular type of S. aureus, but not the only one. Evidence presented in this thesis indicates, for the first time, that the Smith diffuse variant is also encapsulated, as shown by the specific capsular reaction0 The wound mucoid strain and the RLM strain of Price and Kneeland represent members of a major capsular type against which antibodies are widely distributed (Wiley, 1961, 1963). No detectable differences were found between the wound mucoid strain and the Smith diffuse variant, regarding the amount of hemolysin present in cultures. Differences in the amount of coagulase formed by each strain were not great enough to explain the difference in virulence observed. Apparently, the best explanation is that the mice were resistant to the wound strain because they carried it„ and they had elaborated antibodies against it. Our tests did not reveal that mice carried the Smith capsular type of S, aureus, nor could we detect anticapsular antibodies against the latter

Economic impact of reduced mortality due to increased cycling.

Increasing regular physical activity is a key public health goal. One strategy is to change the physical environment to encourage walking and cycling, requiring partnerships with the transport and urban planning sectors. Economic evaluation is an important factor in the decision to fund any new transport scheme, but techniques for assessing the economic value of the health benefits of cycling and walking have tended to be less sophisticated than the approaches used for assessing other benefits. This study aimed to produce a practical tool for estimating the economic impact of reduced mortality due to increased cycling. The tool was intended to be transparent, easy to use, reliable, and based on conservative assumptions and default values, which can be used in the absence of local data. It addressed the question: For a given volume of cycling within a defined population, what is the economic value of the health benefits? The authors used published estimates of relative risk of all-cause mortality among regular cyclists and applied these to levels of cycling defined by the user to produce an estimate of the number of deaths potentially averted because of regular cycling. The tool then calculates the economic value of the deaths averted using the "value of a statistical life." The outputs of the tool support decision making on cycle infrastructure or policies, or can be used as part of an integrated economic appraisal. The tool's unique contribution is that it takes a public health approach to a transport problem, addresses it in epidemiologic terms, and places the results back into the transport context. Examples of its use include its adoption by the English and Swedish departments of transport as the recommended methodologic approach for estimating the health impact of walking and cycling

Ageing and the sustainability of Dutch public finances

The ageing of the population jeopardises the sustainability of public finances in the Netherlands. The doubling of the ratio between the number of retirees and the number of workers destroys the balance between future public expenditure and tax revenues. Read also the accompanying press release .Indeed, the increase in expenditure on public pensions and health and long-term care will outweigh the increase in tax revenues. Budgetary reforms are therefore necessary in order to avoid that future generations will have to raise taxes or economize on public expenditure. Reforms in the field of social security of the last few years are a step in the right direction, but are insufficient. In particular, the decline of interest rates and the reduced wealth of pension funds have worsened the sustainability of public finances. The effects of reforms on the intergenerational balance are important for the question which further reforms are most attractive.

The ACCC's Caltex-Mobil decision: A network view

On December 2nd 2009, the Australian Competition and Consumer Commission (ACCC) announced its intention to oppose the acquisition of Mobil's retail assets by Caltex, based in part on an assessment of adverse competition effects in some local markets. Their assessment was based upon the proportion of sites within each local market that would become controlled by Caltex post-merger. This paper suggests an alternative method foranalysing competitive effects, which formalises local market structure into a network and assesses the position of each outlet in that network

A simple spatial model for Edgeworth cycles

Maskin & Tirole (1998) formalise Edgeworth's (1925) model of a dynamic equilibrium between two players where prices increase sharply and decrease slowly; the Edgeworth Cycle. Here, we present an application of the model, showing how Edgeworth Cycles might arise in a marketplace where spatial competition is important. We illustrate the approach using the example of retail gasoline markets where Edgeworth Cycles have been widely observed

The shape and frequency of Edgeworth price cycles in an Australian retail gasoline market

Gasoline prices in many markets follow a saw-toothed pattern known as an Edgeworth Cycle. Lewis (2009) introduces a novel way of measuring the shape of the cycle, the median change in price, and regresses this against a number of explanatory variables in US markets. Here, we undertake a similar regression analysis, but using data from Perth, Australia, and with a novel measure of market structure as a regressor. We also explore a novel measure, based on spectral analysis, of the use of cycles in a mixed strategy, and the factors which drive this use

Retail gasoline markets as networks

The structure of a gasoline market can be an important element in the pricing choices of its participants. However, structure is often measured only indirectly by, for example, the number of independent sellers, or by seller density. Here we present a more direct and literal way of exploring market structure by representing it as a network. We use the structure of the network to delineate submarkets and present some measures from mathematical sociology which can be used to summarise aspects of network structure for use in further analysis. Although our case study here is in retail gasoline markets, the approach has broader application wherever spatial competition is important

Über die gesellschaftlichen Voraussetzungen und Konsequenzen moderner Produktivkräfte

Wissenschaftliches Kolloquium vom 27. bis 30. Juni 1989 in Weimar an der Hochschule für Architektur und Bauwesen zum Thema: ‚Produktivkraftentwicklung und Umweltgestaltung. Sozialer und wissenschaftlich-technischer Fortschritt in ihren Auswirkungen auf Architektur und industrielle Formgestaltung in unserer Zeit. Zum 100. Geburtstag von Hannes Meyer

Regulation of manganese superoxide dismutase in glomerular epithelial cells: Mechanisms for interleukin 1 induction

Regulation of manganese superoxide dismutase in glomerular epithelial cells: Mechanisms for interleukin 1 induction. Reactive oxygen species have been implicated as mediators of tissue injury in glomerular inflammation. The expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), was examined in primary cultures of rat glomerularepithelial cells (GEC) in response to inflammatory mediators. The results demonstrate that GEC respond to interleukin-1 (IL-1) and bacterial lipopolysaccharride (LPS) with an increase in MnSOD steady-state mRNA levels. The IL-1α-mediated induction of MnSOD mRNA levels was both time- and dose-dependent. Maximal levels, approximately 40-fold above controls, were observed at 12 hours with 2 ng/ml of IL-1α. MnSOD protein levels were also markedly elevated by IL-1α. The induction of MnSOD mRNA by IL-1α required de novo transcription as well as some degree of protein synthesis. To elucidate the potential intracellular signal that mediates IL-1α-dependent MnSOD expression, three classical signaling pathways were examined. We found no evidence that MnSOD induction by IL-lα is mediated by either the cyclooxygenase or lipoxygenase pathway or via activation of protein kinase C. Based on the presence of IL-lα in several forms of glomerular inflammation, the observed increase in MnSOD expression by this immunoregulatory cytokine must have an important role in the antioxidant defense of glomerular epithelial cells